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To evaluate the effectiveness and safety of microvascular decompression (MVD) using a fully transcranial neuroendoscopic approach.Thirty-one patients who underwent MVD using a fully transcranial neuroendoscopic approach in our department between May 2016 and September 2019 were retrospectively reviewed.All patients successfully underwent MVD, and immediate pain relief was achieved in all 17 cases of trigeminal neuralgia (TGH) and 3 cases of glossopharyngeal neuralgia (GPN). Hemifacial spasm (HFS) was completely resolved in all 11 patients. No mortality or permanent complication was seen.The endoscope is a useful tool for confirming vascular conflict identified by the microscope and is helpful in detecting the vessel responsible for neuralgia without retracting the brain and nerves. MVD using a fully transcranial neuroendoscopic approach is an effective and safe alternative to endoscopic-assisted MVD and traditional MVD.

Rho family GTPase 3 (RND3) is involved in multiple physiological activities involving the Rho kinase‑dependent signaling pathway. The present study revealed a novel role of RND3 in the regulation of apoptosis in the brain. Using immunofluorescence and TUNEL assays, a decreased rate of brain apoptosis was observed in Rnd3‑knockout mice. In addition, the function of RND3 in promoting apoptosis was determined in PC12 cells by immunoblotting assays and flow cytometry analysis in RNA interference and overexpression experiments. Furthermore, the present study demonstrated that Rnd3 and P65 protein interacted using immunoprecipitation analysis, and Rnd3 regulated apoptosis via its association with NF‑κB P65. Notably, Rnd3 blocked the anti‑apoptotic action of NF‑κB P65 in vitro by downregulating P65. Therefore, RND3‑NF‑κB P65 represents a novel signaling pathway in the regulation of brain apoptosis. The present study suggested an alternative approach for the treatment of neurodegenerative diseases through regulation of apoptosis via the RND3‑NF‑κB P65 signaling pathway in the central nervous system.

There are various cancer treatments at present, and chemotherapy is one of the main methods. Chemotherapy-related cognitive impairment (CRCI), as one of the side effects of chemotherapy, has gradually attracted the attention of more and more researchers. CRCI has been verified by subjective reports and objective neuropsychological tests so far. But oncologists’ understanding of it and its treatments are still incomplete. In this review, we mainly give a comprehensive overview of the mechanism of CRCI, then describe a variety of evaluation methods, and finally summarize the treatment approaches under current medical conditions and compare it with an excellent article published in 2015 with the aim of providing directions for future research and better understanding of CRCI for clinicians.

Objective: Toutongning (TTN) capsule, a Chinese patent medicine, is used as a prophylactic treatment for migraine. The present study was conducted as a postmarketing evaluation of the efficacy and safety of TTN capsule. Design: A randomized, double-blind, placebo-controlled trial. Location: Patients recruited from 14 medical centers in China from May 2014 to August 2015. Subjects: Patients between 18 and 65 years of age with a diagnosis of migraine. Interventions: The patients were randomly assigned to receive either TTN (1200 mg, three times daily) or a matched placebo (1:1) for 4 weeks. Outcome measures: The primary outcome measured was a minimum 50% reduction in the frequency of headaches from the 4-week baseline period to the last 4 weeks of the 12-week trial. Secondary outcomes included duration, days, and visual analog score of headache attack, interval between headache attacks, usage of acute analgesics, and score on the Headache Impact Test-6. In addition, all patients were evaluated for adverse events (AEs). Results: This study initially enrolled 400 patients; a total of 378 participants completed the experiment while fulfilling all study requirements. TTN had a superior effect compared with the placebo on both the primary and secondary outcome measures without any serious AEs or unexpected side effects. Conclusion: TTN can effectively prevent the occurrence of migraine headaches and is well-tolerated and safe. TTN may exhibit a persistent therapeutic effect even after cessation of use. Trial Registration number: ChiCTR-IPR-15007058.

Objective To evaluate the effectiveness and safety of neuroendoscopic surgery for chronic or subacute subdural hematoma. Patients and methods Between September 2016 and September 2018, neuroendoscopic surgery was performed on 25 patients with chronic and subacute subdural hematoma. Hematoma evacuation was performed with a 0°, 4 mm diameter rigid neuroendoscope via a transcranial neuroendoscopic approach. Results All patients successfully underwent neuroendoscopic surgery, and no surgical complications or rebleeding was observed. Postoperative computed tomography scans showed that the hematoma was successfully evacuated. All patients had recovered well at discharge, the observed 30-day mortality rate was 0%, and no patients suffered recurrence for 2-26 months after surgery. Conclusion Neuroendoscopic surgery was a safe and effective approach for the treatment of chronic and subacute subdural hematoma. This approach has the advantages of decent visualization and minimal invasiveness and could reduce recurrence and the mortality rate.

Background Observational studies, including recent large cohort studies, have reported an association between depression and the risk of Parkinson's disease (PD); however, conclusions were inconsistent. Clarifying this relation might improve the understanding of risk factors for and the disease mechanisms in PD. Therefore, we performed a meta-analysis to examine whether depression is associated with an increased risk of PD. Methods A literature search in the PubMed, EMBASE, Scopus, PsycINFO and Web of Science databases was undertaken through March 2018, looking for observational studies evaluating the association between depression and the risk of PD. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also performed. Results A random-effects meta-analysis of 5 cohort studies and 6 case-control studies demonstrated a significant positive association between depression and a subsequent risk of PD (RR, 2.20; 95% CI, 1.87–2.58), and it was consistent across subgroups. Furthermore, sensitivity analysis confirmed the stability of the results; visual examination of funnel plots and Begg's and Egger's tests showed no evidence of publication bias. Conclusions Our meta-analysis demonstrated that persons with depression exhibited an increased risk of a subsequent PD diagnosis. The pathophysiological and psychological mechanisms underlying this association are still unclear and warrant further research.

Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro, resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP+). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay. We found that MPP+ induced neuronal death and the activation of caspase-3 in a dose-dependent manner. The expression of DNA pol-β increased after the neurons were exposed to MPP+. DNA pol-β siRNA or DNA pol-β inhibitor DDC attenuated neuronal death induced by MPP+. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, MPTP treatment triggered behavioral deficits and nigrostriatal lesions. Pretreatment with DDC attenuated MPTP-induced behavioral deficits, dopaminergic neuronal death and striatal dopamine depletion in the MPTP mouse model. These results indicate that DNA pol-β inhibitors may present a novel promising therapeutic option for the neuroprotective treatment of PD.

Neurological function deficits due to cerebral ischemia or neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) have long been considered a thorny issue in clinical treatment. Recovery after neurologic impairment is fairly limited, which poses a major threat to health and quality of life. Accumulating evidences support that ROS and autophagy are both implicated in the onset and development of neurological disorders. Notably, oxidative stress triggered by excess of ROS not only puts the brain in a vulnerable state but also enhances the virulence of other pathogenic factors, just like mitochondrial dysfunction, which is described as the culprit of nerve cell damage. Nevertheless, autophagy is proposed as a subtle cellular defense mode against destructive stimulus by timely removal of damaged and cytotoxic substance. Emerging evidence suggests that the interplay of ROS and autophagy may establish a determinant role in the modulation of neuronal homeostasis. However, the underlying regulatory mechanisms are still largely unexplored. This review sets out to afford an overview of the crosstalk between ROS and autophagy and discusses relevant molecular mechanisms in cerebral ischemia, AD, and PD, so as to provide new insights into promising therapeutic targets for the abovementioned neurological conditions.

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder mainly in middle-elderly population, which represents diverse nonmotor symptoms (NMS) besides such well-documented motor symptoms as bradykinesia, resting tremor, rigidity, and postural instability. With the advancement of aging trend worldwide, the global prevalence of PD is mounting up year after year. Nowadays, accumulating lines of studies have given a comprehensive and thorough coverage of motor symptoms in PD. Yet much less attention as compared has been paid to the nonmotor symptoms of PD, such as cognition deficits. Of note, a patient with PD who suffers from cognitive impairment may harbour a statistically significantly higher risk of progressing toward dementia, which negatively affects their life expectancy and daily functioning and overall lowers the global quality of life. Furthermore, it is a widely held view that cognitive dysfunction does not just occur in the late stage of PD. On the basis of numerous studies, mild cognitive impairment (MCI) is a harbinger of dementia in PD, which is observed as an intermediate state with considerable variability; some patients remain stable and some even revert to normal cognition. Considered that the timing, profile, and rate of cognitive impairment vary greatly among PD individuals, it is extremely urgent for researchers and clinicians alike to identify and predict future cognitive decline in this population. Simultaneously, early screening and canonical management of PD with cognitive deficits are very imperative to postpone the disease progression and improve the prognosis of patients. In our review, we focus on a description of cognitive decline in PD, expound emphatically the pathological mechanisms underlying cognition deficits in PD, then give a comprehensive overview of specific therapeutic strategies, and finally dissect what fresh insights may bring new exciting prospect for the subfield.

Depressive and anxiety symptoms are frequently observed in breast cancer survivors. To date, few randomized controlled trials have been conducted on the efficacy of cognitive behavioural therapy (CBT) for depressive and anxiety symptoms in Chinese population. This study aims to verify the efficacy of CBT in Chinese breast cancer survivors. Women (n = 392) with breast cancer were randomly assigned to 3 groups: CBT (n = 98), self-care management (SCM, n = 98), and usual care (UC, n = 196) using the proportion 1:1:2. Women in the CBT and SCM groups received a series of nine sessions for 12 weeks, while women in the UC group received their usual medical care only. Depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) score at baseline, 2, 4, 8, 12, 16, and 24 weeks. A significant intergroup difference was found in the HAMD and HAMA scores. Women in the CBT group showed significantly less depressive and anxiety symptoms compared with women in the SCM and UC groups over time. In conclusion, this study supports the efficacy of CBT for depressive and anxiety symptoms in Chinese breast cancer survivors.

Cardiovascular disease (CVD) caused by atherosclerosis is one of the major causes of death world-wide. Currently, diverse machine learning models have been applied to disease prediction and classification. However, most of them tend to focus on the performance of the algorithm and neglect the underlying variables for patients in different carotid atherosclerotic stages. In this paper, we propose a novel hybrid machine learning method named Subset Learning (S-learning) to predict and discover the risk factors of these different stages. The S-learning algorithm can elucidate the variables that have significant influence on the outcome of carotid atherosclerotic. Performance comparisons are based on the dataset collected from both Shanghai Renji and Shanghai Huashan Hospital. The result shows that the proposed method has superior classification performance than other classification algorithms. Our findings point to the utility of predictive machine learning and the discovery of risk factors to refine the treatment plans.

Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. Identification of RND3 as a novel factor in GBM genesis was demonstrated in vitro by cell experiments and in vivo by a GBM xenograft model. We found that RND3 expression was significantly decreased in human glioblastoma. The levels of RND3 expression were inversely correlated with Notch activity, tumor size, and tumor cell proliferation, and positively correlated with patient survival time. We demonstrated that RND3 functioned as an endogenous repressor of the Notch transcriptional complex. RND3 physically interacted with NICD, CSL, and MAML1, the Notch transcriptional complex factors, promoted NICD ubiquitination, and facilitated the degradation of these cofactor proteins. We further revealed that RND3 facilitated the binding of NICD to FBW7, a ubiquitin ligase, and consequently enhanced NICD protein degradation. Therefore, Notch transcriptional activity was inhibited. Forced expression of RND3 repressed Notch signaling, which led to the inhibition of glioblastoma cell proliferation in vitro and tumor growth in the xenograft mice in vivo. Downregulation of RND3, however, enhanced Notch signaling activity, and subsequently promoted glioma cell proliferation. Inhibition of Notch activity abolished RND3 deficiency-mediated GBM cell proliferation. We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis.

Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro, resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

// Baohui Liu 1, * , Huimin Dong 1, * , Xi Lin 2 , Xiangsheng Yang 2 , Xiaojing Yue 2 , Jian Yang 1 , Yuntao Li 1 , Liquan Wu 1 , Xiaonan Zhu 1 , Shenqi Zhang 1 , Daofeng Tian 1 , Junmin Wang 1 , Qiang Cai 1 , Shanping Mao 3 , Qianxue Chen 1 , Jiang Chang 2 1 Department of Neurological Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China 2 Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA 3 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China * These authors contributed equally to this work Correspondence to: Jiang Chang, email: jchang@ibt.tamhsc.edu Qianxue Chen, email: chenqx666@sohu.com Keywords: RND3, multiform glioblastoma, snail1 signaling Received: May 20, 2016 Accepted: September 24, 2016 Published: October 01, 2016 ABSTRACT Activation of Snail1 signaling promotes the migration and invasion of multiple tumors, including glioblastoma multiforme (GBM). However, the molecular mechanism that augments Snail1 signaling during GBM cell migration and invasion remains largely unknown. Identification of the factors that regulate Snail1 signaling is critical to block tumor cell migration and invasion. By screening human GBM specimens, we found that the expression levels of small GTPase RND3 positively correlated with the expression levels of E-cadherin and claudin, the glioblastoma migration biomarkers negatively regulated by Snail1. Downregulation of E-cadherin and claudin has been associated with the migration and invasion of GBM cells. We demonstrated that RND3 functioned as an endogenous inhibitor of the Snail-directed transcriptional regulation. RND3 physically interacted with Snail1 protein, enhanced Snail1 ubiquitination, and facilitated the protein degradation. Forced expression of RND3 inhibited Snail1 activity, which in turn blocked glioblastoma cell migration and invasion in vitro in cell culture and in vivo in GBM xenograft mice. In contrast, downregulation of RND3 augmented Snail1 activity, and subsequently decreased E-cadherin expression, eventually promoted glioblastoma cell migration and invasion. The pro-migration induced by RND3 downregulation was attenuated by Snail1 knockdown. The findings partially explain why Snail1 activity is augmented in GBM, and defines a new function of RND3 in GBM cell migration and invasion.

For the aging populations of any nation, Dementia is becoming a primary problem and Alzheimer’s dementia (AD) is the most common type. However, until now, there is no effective treatment for AD. Tanshinone IIA (Tan IIA) has been reported for neuroprotective potential to against amyloid β peptides (Aβ)-induced cytotoxicity in the rat pheochromocytoma cell line PC-12, which is widely used as AD research model, but the mechanism still remains unclear. To investigate the effect of Tan IIA and the possible molecular mechanism in the apoptosis of PC12 cells, we induced apoptosis in PC12 cells with β-amyloid(25-35), and treated cells with Tan IIA. After 24 h treatment, we found that Tan IIA increased the cell viability and reduced the number of apoptotic cells induced by Aβ(25-35). However, neuroprotection of Tan IIA was abolished by PI3K inhibitor LY294002. Meanwhile, Treatment with lithium chloride, a phosphorylation inhibitor of GSK3β, which is a downstream target of PI3K/Akt, can block Aβ(25-35)-induced cell apoptosis in a Tan IIA-like manner. Our findings suggest that Tan IIA is an effective neuroprotective agent and a viable candidate in AD therapy and PI3K/Akt activation and GSK3β phosphorylation are involved in the neuroprotection of Tan IIA.

To generate a digital brain atlas, we need to segment and extract brain structures from images of an individual brain. However, many of the brain structures can hardly be accurately segmented if only according to the content of them. The goal of this thesis is to develop an experiment platform, which focuses on the basic methods about labeling, extraction, segmentation and visualization brain structures in MR images by leveraging the anatomic information and topological structure in standard atlas. In this paper, we propose the concept of standardization of brain MR image and introduce a king of standardization method based on geometry correction technique. To work out the method, first we preprocessed the raw MR image, second automatically searched the control points which were used for establishing the correction equation, and last we completed the standardization of the MR image. The result of the experiments demonstrated the practicability efficiency of this kind of method, which could provide theoretical foundation and experimental means for the diagnosis of brain disease.