Functional connectivity alterations in the frontoparietal network and sensorimotor network are associated with behavioral heterogeneity in blepharospasm.

Objective: Primary blepharospasm (BSP) is a clinically heterogeneous disease that manifests not only as spasmodic closure of the eyelids but also sometimes with apraxia of eyelid opening (AEO). This cross-sectional study aimed to investigate differences in the neural mechanisms of isolated BSP and BSP-associated AEO subtypes, which may reveal the pathophysiology underlying different phenotypes. Methods: A total of 29 patients manifested as isolated BSP, 17 patients manifested as BSP associated with AEO, and 28 healthy controls underwent resting-state functional near-infrared spectroscopy (fNIRS). We assessed functional connectivity (FC) between regions of interest (ROIs) in the fronto-parietal control network (PFCN) and sensorimotor network (SMN). We also examined the relationship between altered FC and behavioral data. Results: In the FPCN, ROI- analyses showed decreased FC between the left premotor cortex and supramarginal gyrus in the BSP with AEO group compared to the isolated BSP group. In the SMN, both subgroups showed hypoconnectivity of the left premotor cortex with the right primary motor cortex, primary sensory cortex, and somatosensory association cortex. This hypoconnectivity was positively correlated with the total number of botulinum toxin A treatments, which suggests that long-term botulinum toxin A treatment may modulate motor sequence planning and coordination. Conclusion: These findings showed different connectivity alterations in neural networks associated with motor and cognitive control among different behavioral phenotypes of BSP. The identification of specific alterations in various networks that correspond to clinical heterogeneity may inform the identification of potential biomarkers for early diagnosis and personalized neuromodulation targets for treating different BSP subphenotypes.

Update on the clinical application of deep brain stimulation in sleep dysfunction of Parkinson's disease.

Sleep dysfunctions, including rapid eye movement sleep behavior disorder, sleep fragmentation, excessive daytime sleepiness and various other dysfunctions, can seriously affect quality of life in patients with Parkinson's disease (PD). Emerging evidence suggests that deep brain stimulation (DBS) exerts a substantial effect when used to treat sleep dysfunctions, which are common nonmotor symptoms experienced by patients with PD. However, far less is known about the specific mechanisms underlying the effects of DBS on sleep processes and the factors that potentially influence these effects. These issues therefore need to be further clarified. Intriguingly, a number of recent studies have evaluated the effects of applying DBS to various brain targets on sleep in patients with PD. Deeper research into the efficacy of applying DBS to each brain target may help determine which region should be targeted during surgery in PD patients. Furthermore, compared with pharmacological therapy, DBS had more beneficial effects on sleep symptoms, and appropriate management involving the joint application of dopamine replacement therapy and DBS might accelerate the effects of treatment. Here, we review the potential roles DBS may play and provide clinical guidance for the use of DBS in treating sleep dysfunctions in PD patients.

[Prognostic Significance of ERG Gene Rearrangement and Protein Expression in Prostate Cancer].

OBJECTIVES: To investigate gene rearrangement and protein expression of ETS related gene (ERG ) in prostate cancer of Chinese patients and its correlation with clinicopathological characteristics and prognosis. METHODS: This study collected 482 cases of prostatic adenocarcinomas diagnosed by prostate biopsy in West China Hospital of Sichuan University from 2009 to 2014. Fluorescencein situ hybridization (FISH) and immuno-histochemical staining (IHC) were performed to access the ERG rearrangement and protein expression respectively. Relationship between ERG rearrangement and protein expression was assessed by Spearman rank order correlation. The correlations of ERG rearrangement and protein expression with clinicopathological variables and prognosis were further analyzed. RESULTS: ERG rearrangement was detected in 87 (18.0 %) cases, of which 45 (51.7%) was translocation and 42 (48.3%) was deletion. ERG protein expression was detected in 74 (15.4%) cases. Follow-up data was obtained in 368 cases. ERG rearrangement and protein expression had no correlations to age, Gleason score and pre-operation PSA level ( P>0.05), but ERG protein level was decreased in metastatic cases or castration resistant prostate cancer (CRPC) cases ( P<0.05) . Kaplan-Meier curve showed both gene rearrangement and protein expression of ERG had no prognostic significance. CONCLUSIONS: ERG rearrangement, as well as ERG protein expression, could not serve as an independent prognostic biomarker.

Early application of citicoline in the treatment of acute stroke: A meta-analysis of randomized controlled trials.

This study was to evaluate the efficacy and safety of early application of citicoline in the treatment of patients with acute stroke by meta-analysis. Randomized controlled trials published until May 2015 were electronically searched in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registration Platform, Clinical Trial.gov, and China Biology Medicine disc. Two reviewers independently screened the articles and extracted the data based on the inclusion and exclusion criteria. The quality of included articles was evaluated by using Revman5.0, and meta-analysis was performed. The results showed that 1027 articles were obtained in initial retrieval, and finally 7 articles, involving a total of 4039 cases, were included for analysis. The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. The overall rate of adverse events in citicoline group was not significantly different from that in control group (P=0.30). The quality of included articles reached moderate-low level. In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety.

Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2.

BACKGROUND: Icariine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts. METHODS: Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells (hMSCs) directionally and were cultured in the presence of various concentrations of Icariine. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 (BMP-2) mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Icariine (20 microg/ml) increased significantly the proliferation of human osteoblasts. And, Icariine (10 microg/ml and 20 microg/ml) increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly (P < 0.05). BMP-2 mRNA synthesis was elevated significantly in response to Icariine (20 microg/ml). CONCLUSIONS: Icariine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.

[Effects of Epimedium pubescens icariine on proliferation and differentiation of human osteoblasts].

OBJECTIVE: To study the effects of epimedium pubescens icariine on the proliferation and differentiation of human osteoblasts. METHOD: Human osteoblasts were obtained by inducting human marrow mesenchymal stem cells (hMSCs) directionally. MTT was used to observe the proliferation and activity of ALP was assayed to observe the differentiation of the third passage human osteoblasts cultured in vitro. The expression of BMP-2 mRNA was checked by RT-PCR. RESULT: Epimedium pubescens icariine at the dose of 20 microg x mL(-1) increased greatly the proliferation and differentiation of human osteoblasts and promoted the expression of BMP-2 mRNA. CONCLUSION: Epimedium pubescens icariine enhances significantly the proliferation and differentiation of human osteoblasts, which may be mediated by increasing the expression of BMP-2 mRNA.

[Inducing human marrow mesenchymal stem cells into osteoblasts directionally and identification of their osteogenesis characteristics].

OBJECTIVE: To study the method of inducing human marrow mesenchymal stem cells (MSCs) into osteoblasts directionally and to identify osteogenesis characteristics. METHODS: MSCs were isolated from adult marrow using density gradient separation method and were cultured in conditioned medium containing Dex 10(-8) mol/L, beta-GP 10 mmol/L, and AA 50 micrograms/ml. The MSCs attachment formed soon and passage 3 cells were chosen to check osteogenesis characteristics, including alkaline phosphatase assay with modified calcium-cobalt staining method, type I collagen assay with immunohistochemistry, osteopontin and osteonectin assay with in situ hybridization and calcium nodes assay with Von Kossa staining. RESULTS: Passage 3 MSCs had typical appearance of osteoblasts and could be passaged continuously till passage 10. The rate of ALP expression was 85%. The expressions of collagen type I, osteopontin and osteonectin were positive and calcium nodes were seen by Von Kossa staining. CONCLUSION: We have successfully induced human MSCs into osteoblasts; the induced cells have typical osteogenesis characteristics.

[Immortalization of human osteoblast by transferring hTERT gene].

OBJECTIVE: To establish an immortalized osteoblast cell line used for basal and clinical research of orthopaedics. METHODS: Human marrow stromal cells (hMSCs) had been inducted into osteoblasts directionally, and human telomerase reverse transcriptase (hTERT) cDNA was transferred into the osteoblasts by retroviral vector pLPChTERT. The resultant stable clones reproduced successively and the expression of hTERT as well as the osteogenesis characteristics of different eras were identified. RESULT: hTERT gene has been transferred into human osteoblasts successfully. The transformed cells expressed telomerase activity and divided vigorously. p62 has been obtained so far. The expression of bone specific Alkaline phosphatase, Collagen type I and Osteopontin of p25, p55 were checked and it is proved that the immortalized cell line preserved typical osteogenesis characteristics. CONCLUSION: Osteoblasts can be immortalized by transferring exogenous hTERT gene to reconstitute telomerase activity, and the immortalized cell reserved osteogenesis characteristics.