Fang Yang

Effects of repetitive transcranial magnetic stimulation on motor recovery and motor cortex excitability in patients with stroke: a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) changes the excitability of the motor cortex and thereby has the potential to enhance motor recovery after stroke. This randomized, sham‐controlled, double‐blind study was to compare the effects of high‐frequency versus low‐frequency rTMS on motor recovery during the early phase of stroke and to identify the neurophysiological correlates of motor improvements.

Quantitative analysis of dietary protein intake and stroke risk

Objective: To perform a meta-analysis of prospective studies to evaluate the relation between dietary protein intake and stroke risk. Methods: Relevant studies were identified by searching PubMed and Embase through November 2013, and by reviewing the reference lists of retrieved articles. We included prospective cohort studies that reported relative risks (RRs) with 95% confidence intervals (CIs) for the association between dietary protein intake and stroke risk. Results: The meta-analysis included 7 prospective studies involving 254,489 participants. The pooled RR of stroke for the highest compared with the lowest dietary protein intake was 0.80 (95% CI 0.66–0.99). Dose-response analysis indicated that a 20-g/d increment in dietary protein intake was associated with a 26% reduction in stroke risk. Stratifying by protein type, the RR of stroke for animal protein was 0.71 (95% CI 0.50–0.99). Sensitivity analysis restricted to studies with control for common risk factors yielded similar results, and omission of any single study did not change the overall result. Conclusion: These findings suggest that moderate dietary protein intake may lower the risk of stroke.

Tissue kallikrein protects cortical neurons against hypoxia/reoxygenation injury via the ERK1/2 pathway

Systemic or local delivery of human tissue kallikrein gene (hTK) has been shown to be an effective strategy to alleviate cerebral ischemia/reperfusion (I/R) injury, and tissue kallikrein (TK) administration can suppress glutamate- or acidosis-mediated neurotoxicity in vitro. In the present study, the role of TK in hypoxia/reoxygenation (H/R) induced neuronal cell death was investigated. We found that TK administration could remarkably alleviate H/R-induced neuronal injury by reduction of LDH release and promotion of neuron viability. The protective effects of TK could be counteracted by bradykinin B2 receptor (B2R) antagonist HOE140, which could suppress up-regulation of TK on the ERK signal pathway under H/R condition. These results indicate that TK plays an important role in preventing neurons from H/R damage at least partially through the TK-B2R-ERK1/2 pathway.

Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer.

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy.

AbstractRecurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a “conscious perception network,” which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.

Neutrophil-to-Lymphocyte Ratio Predicts Length of Stay and Acute Hospital Cost in Patients with Acute Ischemic Stroke

BACKGROUND Although several risk factors for prolonged length of stay (LOS) and increased hospital cost have been identified, the association between LOS, hospital cost, and neutrophil-to-lymphocyte ratio (NLR) has not yet been investigated. We aimed to investigate the influence of NLR on LOS and hospital cost in patients with acute ischemic stroke. METHODS Patients with acute ischemic stroke diagnosed within 24 hours of symptom onset were included. Univariate analysis and stepwise multiple regression analysis were used to identify independent predictors of LOS and hospital cost. RESULTS A total of 346 patients were included in the final analysis. The median LOS was 11 days (range 8-13 days). The median acute hospital cost per patient was 19,030.6 RMB (U.S.

Repetitive transcranial magnetic stimulation for rehabilitation of poststroke dysphagia: A randomized, double-blind clinical trial.

3065.8) (range 14,450.8 RMB-25,218.2 RMB). Neutrophil count to lymphocyte count (NLR) (P < .001), diabetes mellitus (P = .034), stroke subtype (P = .005), and initial stroke severity (P < .001) were significantly associated with prolonged LOS in the univariate analysis. NLR (P < .001), smoking (P = .04), stroke subtype (P < .001), initial stroke severity (P < .001), and LOS (P < .001) were significantly associated with increased hospital cost in the univariate analysis. Multivariate regression analysis showed that NLR was an independent predictor of both LOS and acute hospital cost. In addition, high NLR was significantly correlated with poor outcome at discharge, prolonged LOS, and increased hospital cost. CONCLUSIONS NLR is significantly associated with LOS and acute hospital cost in patients presenting with acute ischemic stroke. It is a simple, inexpensive, and readily available biomarker and may serve as a clinically practical indicator for assessing the economic burden of stroke.

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

OBJECTIVE This randomized, sham-controlled, double-blind study was conducted to investigate the effects of high-frequency versus low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with poststroke dysphagia during early rehabilitation. METHODS Forty patients with poststroke dysphagia were randomized to receive five daily sessions of sham, 3-Hz ipsilesional, or 1-Hz contralesional rTMS. Swallowing function, the severity of stroke and functional disability, and cortical excitability were examined before, immediately after five daily sessions, as well as the first, second, and third month after the last session. RESULTS At baseline, no significant differences between groups were observed in terms of demographic and clinical rating scales. However, a significantly greater improvement in swallowing function as well as functional disability was observed after real rTMS when compared with sham rTMS, which remained 3 months after the end of the treatment sessions. In addition, 1-Hz rTMS increased cortical excitability of the affected hemisphere and decreased that of the non-affected hemisphere; however, 3-Hz rTMS only increased cortical excitability of the affected hemisphere. CONCLUSION rTMS (both high and low frequency) improved swallowing recovery in patients with poststroke dysphagia, and the effects lasted for at least 3 months. SIGNIFICANCE rTMS appears to be a beneficial therapeutic modality for patients with dysphagia during the early phase of stroke.

Pattern of cerebrovascular atherosclerotic stenosis in older Chinese patients with stroke

Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44+/CD24-, aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases. We found that a few patients displayed spatial heterogeneity of the BCSC markers in expression, which was defined as intratumor stemness heterogeneity (ITSH) below. There was no significant correlation between any BCSC marker alone or ITSH and progression-free survival (PFS). Interestingly, the combined BCSC phenotype by CD44+/CD24- and ALDH1A1 was significantly associated with worse PFS (P = 0.009). Further stratification analysis revealed that this combined BCSC phenotype was an independent prognostic factor for PFS in some subgroups. In conclusion, we demonstrated the existence of ITSH in TNBC and found that the ITSH as well as a single BCSC marker was not significantly associated with survival, whereas combing the analysis of BCSC markers could improve prognostic value. Our findings may lead to an improvement of prognostic indicators in TNBC.

More Severe Extratemporal Damages in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis Than That With Other Lesions: A Multimodality MRI Study.

The clinical pattern and angiographic distribution of cerebral atherosclerosis varies among different ethnic groups. This study was designed to identify the clinical background for intracranial and extracranial atherosclerotic stenosis in older eastern Chinese patients using digital subtraction angiography. We retrospectively reviewed the data collected from the Nanjing Stroke Registry Program, from January 2004 to March 2011. The analysis focused on the intracranial or extracranial location of stenosis in the anterior and posterior circulations. In total, records of 1041 patients were included in the study. Of these patients, 19.88% had intracranial carotid stenosis, 18.73% had stenosis in the extracranial vessels, and 33.33% had concurrent stenoses. A total of 2002 stenotic sites were detected in 749 patients. Among those patients with stenosis, a single stenosis was found in 170 (16.33%) and multiple stenoses were found in 579 (55.62%). The prevalence of intracranial stenosis in the single-stenosis group was 54.12%, while in the multiple-stenosis group it was 47.87% (p=0.127). A higher incidence of severe stenosis (70-99% blockage) and occlusion was found in the intracranial vessels than in the extracranial vessels (p=0.018). Older Chinese patients with atherosclerotic stenosis tend to have more intracranial stenoses.