Wenli Hu

The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine – Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model

Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.

Infarct Size May Distinguish the Pathogenesis of Lacunar Infarction of the Middle Cerebral Artery Territory

Background Lacunar infarctions are caused by small vessel disease (SVD) and branch atheromatous disease (BAD). Lacunar infarction may be classified as proximal vessel lacunar infarction (BAD) or distal vessel lacunar infarction (SVD) according to its location within the middle cerebral artery (MCA) territory in patients with normal MCA. Studies found that the lenticulostriate arteries may exist different ways and that the size of lacunar infarction may be dependent on the branching order. We investigated whether lacunar infarction size can differentiate between SVD and BAD in patients with normal MCA. Material/Methods We retrospectively studied 312 patients with lacunar infarction who had normal MCA on MR angiography. We found the normal flow void of the MCA on MR T2-weighted images, and the same layer on DWI was considered the level 0. The median of lowest layer of infarction lesions and the mean of lesion size were considered the cutoff point. We divided lacunar infarction into 2 groups according to cutoff point of lesion location and size. Data compared between the 2 groups included clinical information, radiography, and National Institutes of Health Stroke Scale score. Results Of all the 312 patients, the median of lowest layer of infarction lesions was the 3rd level. Compared to patients with BAD, according to infarct location, patients with SVD were older, more often had a history of hypertension and smoking, and had more severe leukoaraiosis and smaller infarct lesions. The mean length of lesions was 11.1 mm on DWI images. Patients with SVD, according to infarct size, had lower NIHSS scores at admission. The mean lesion height was 12.26 mm on FLAIR images. Patients with SVD were more often male, had higher prevalence of smoking, and had more severe leukoaraiosis and lower NIHSS scores at admission. The lacunar infarction diameter on DWI and FLAIR images was negatively correlated with the level of lowest layer of infarction lesions. Conclusions Our data suggest that infarct lesion size may be used as a method to distinguish SVD and BAD in lacunar infarction patients with normal MCA.

Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients.

Background Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. Methods We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. Results During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. Conclusions Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia.

Meta-analysis of the association between serum iron levels and Parkinson's disease: Evidence from 11 publications

BACKGROUND There is no consensus on the serum iron levels and Parkinsons disease (PD). The aim of this study is to conduct a systematic review and meta-analysis to analyse the relationship between serum iron levels and PD risk. METHODS We searched the databases of PubMed, Web of knowledge, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medical literature to assess the association between serum iron levels and PD risk. Standardized mean differences (SMD) and 95% confidence intervals (CI) with random-effect model were used to combine the results. RESULTS Eleven related articles met our selection criteria and contained a total of 829PD patients and 1219 healthy controls. Our meta-analysis results revealed that the serum iron levels in PD patients were significantly higher than those in healthy controls (SMD=0.27, 95% CI=0.18, 0.37, P<0.001). Subgroup analysis by ethnicity showed that the serum iron levels in PD patients were significantly higher than controls both in Asian populations and European populations. Significant associations were also found in prospective studies and case-control studies. CONCLUSIONS Our meta-analysis showed strong evidence that a significantly higher serum iron levels are present in PD patients when compared to the healthy controls.

The significant effects of cerebral microbleeds on cognitive dysfunction: An updated meta-analysis

Objective Accumulated data suggests that cerebral microbleeds (CMBs) play an important role in the decline of cognitive function, but the results remain inconsistent. In the current study, we aimed to investigate the association between CMBs and cognitive function, as well as the various effects of CMBs on different domains of cognition. Methods We searched through the databases of PubMed, Embase, Cochrane Library, and ScienceDirect. After a consistency test, the publication bias was evaluated and a sensitivity analysis was performed with combined odds ratios (OR) and standardized mean difference (SMD) of CMBs. Results A meta-analysis of 25 studies with 9343 participants total was conducted. Patients with CMBs had higher incidence of cognitive impairment (OR:3.5410; 95% confidence interval [CI] [2.2979, 5.4567], p<0.05) and lower scores of cognitive functions (SMD: -0.2700 [-0.4267, -0.1133], p<0.05 in Mini-Mental State Examination [MMSE] group and -0.4869 [-0.8902, -0.0818], p<0.05 in Montreal Cognitive Assessment [MoCA] group). Our results also indicated that patients with CMBs had obvious decline in cognitive functions, for instance, orientation (SMD: -0.9565 [-1.7260, -0.1869], p<0.05), attention and calculation (SMD: -1.1518 [-1.9553, -0.3484], p<0.05) and delayed recall (SMD: -0.5527 [-1.1043, -0.0011], p = 0.05). Conclusions Our data suggested that CMBs might be an important risk factor for cognitive dysfunction, especially in the domains of orientation, attention and calculation and delayed recall functions. Prospective cohort studies with further investigations will be needed in larger samples.

The effect of activin A on signal transduction pathways in PC12 cells subjected to oxygen and glucose deprivation

The processes and mechanisms underlying brain injuries due to ischemia and anoxia have yet to be determined. Additionally, few clinical treatements are currently available. Activins have a protective role in the restoration, differentiation, and survival of injured cells, including Activin A (ActA), which acts as a neuroprotectant. However, its exact mechanism of action remains to be determined. ActA has been shown to protect neurons following ischemic brain injury. In this study, PC12 cells were differentiated into neuron-like cells after stimulation with nerve growth factor to prepare an oxygen/glucose deprivation (OGD) model in neurons. The differentiated PC12 cells, subjected to the OGD model, were exposed to ActA. Results showed that the PC12 survival rate decreased after OGD, leading to an increase in caspase-3 expression in these cells. Pretreatment with ActA was able to partially prevent OGD-induced apoptosis, likely through the downregulation of caspase-3. Futhermore, ActA pretreatment increased the expression of key proteins in the ActA/Smads signal transduction pathway, which may promote neuroprotection after OGD. Therefore, exogenous ActA may function as a neuroprotectant and provide a novel therapeutic treatment for ischemic brain injury.

Emodin prevents hypoxic-ischemic neuronal injury (Involvement of the activin A pathway)

Emodin, an extract of dried rhizomes and the root of the Rhizoma Polygoni Cuspidati, can protect neurons from hypoxic-ischemic brain damage. This study aimed to verify the underlying mechanism. After PC12 cells had differentiated into neuron-like cells under the induction of mouse nerve growth factor, cells were subjected to oxygen-glucose deprivation and treated with emodin. Results showed that the viability of neuron-like cells cultured under an ischemia-hypoxia environment decreased, while the expression of activin A and caspase-3 in cells increased. Emodin raised the survival rate of oxygen-glucose deprived neuron-like cells, increased activin A expression, and decreased caspase-3 expression. Experimental findings indicate that emodin can inhibit neuronal apoptosis and alleviate the injury of nerve cells after oxygen-glucose deprivation through the activin A pathway.

Factors Associated with Benign Paroxysmal Positional Vertigo: A Chinese Case-Control Study

Background Benign paroxysmal positional vertigo (BPPV) is one of the most common and most successfully treated vestibular disorders. However, there is a lack of predictive factors for BPPV in clinical practice. We aimed to explore several possible predictive factors for BPPV in the Chinese population. Material/Methods We enrolled 240 patients with BPPV from Beijing Chaoyang Hospital between July 2013 and July 2016. Biochemical and hematological markers were obtained along with the history of cardiovascular and cerebrovascular diseases. Results Serum uric acid (SUA) [279.0±84.7 vs. 331.0±82.7], hemoglobin A1C (HbA1c) [5.75±1.17 vs. 6.61±1.00], albumin [38.1±3.71 vs. 40.9±4.1], and creatinine [68.4±19.3 vs. 81.5±24.1] were significantly lower in patients with BPPV compared with controls (P<0.05). Multiple logistic regression analysis showed that lower levels of HbA1c and albumin were independently associated with BPPV (P<0.05), with odds ratio (OR) 0.680 (95% CI 0.551–0.839) and 0.338 (95% CI 0.190–0.603), respectively. However, the level of SUA was not independently related with BPPV [OR=0.999 (95% CI 0.991–1.006), P=0.713]. There were no significant differences between the parameters of systolic blood pressure, diastolic blood pressure, blood routine examination, lipid profiles, homocysteine, pre-albumin, and blood urea nitrogen in patients with BPPV vs. controls (P>0.05). Conclusions Lower levels of HbA1c and albumin were independently associated with BPPV. Although the level of SUA was lower in BPPV patients, SUA was not an independent risk factor for BPPV.

Disconnections of Cortico-Subcortical Pathways Related to Cognitive Impairment in Patients with Leukoaraiosis: A Preliminary Diffusion Tensor Imaging Study

Background: We aimed to explore the relation between the microstructural integrity of white matter using the technique of diffusion tensor imaging (DTI) and changes of cognition in leukoaraiosis (LA). Methods: Fifty patients with LA and 50 age- and gender-matched controls were recruited consecutively. The average values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal-appearing white matter (NAWM) from the regions of interest (ROIs). Results: We found significantly decreased FA and increased MD in WMLs at the 5 ROIs than that in NAWM and controls (p < 0.05). The values of FA in NAWM were significantly lower at centrum semiovale and posterior periventricular white matter than those of controls (p < 0.05). The values of MD in NAWM were significantly higher at the anterior periventricular white matter and corpus callosum than those of controls (p < 0.05). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.420, p = 0.028). Conclusions: DTI may provide some important information about the cognitive dysfunction in patients with LA, which may largely attribute to the “disconnection” of cortico-subcortical pathways, with the evidence of reduced FA and increased MD.

Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients

Background Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients. Methods Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated. Results 33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019–1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105–4.978) were independent risk factors for development of MODS. Conclusions In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS is critical important.