Objective To investigate the incidence rate, onset time and electrophysiological characteristics of rapid eye movement sleep behavior disorder (RBD) and the relationship between RBD and synucleinopathies as well as the electrophysiological diagnostic criteria of RBD in Parkinson' s disease (PD) and multiple system atrophy (MSA). Methods Sleep survey and night video-polysomnography (NPSG)were used to study sleep disturbance of PD and MSA. (1) Subjective sleep assessments: All subjects,including 66 PD patients, 65 age and sex matched healthy controls and 30 MSA patients, completed the sleep questionnaires, and the RBD incidence rate and onset time were got. (2) Objective sleep assessments: 8 PD patients, 13 MSA patients, and 15 age and sex matched healthy controls underwent video-NPSG recording on two consecutive nights. Sleep architect were analyzed. The NPSG characteristics of RBD accompany with PD and MSA were analyzed, and the electrophysiological diagnostic varameters of it were determined. Results Patients with PD or MSA had a higher prevalence of RBD. RBD was found in 59. 1% (39/66) PD patients and 86. 6% (26/30) MSA patients, among those, 46. 2% ( 18/39 ) and 84.6% (22/26) had the waking symptoms of MSA and PD. The main NPSG characteristics of RBD of PD or MSA were chin REM without atonia (RWA) and increased movement. Conclusions The relatively higher RBD prevalence in MSA and PD patients indicates that RBD has close relationship with PD and MSA.Part of patients with RBD preceding neurology disease indicates that RBD may be the early marker of PD and MSA. The main NPSG characteristics of RBD accompany with PD and MSA are chin RWA and the motor manifestations. RWA and phasic EMG activity density are supposed to be the NPSG diagnostic parameters.

Objective To describe the clinical spectrum,especially sleep disorder in three patients diagnosed with Morvan syndrome.Methods Three consecutive patients were identified with Morvan syndrome in the Department of Neurology, Peking Union Medical College Hospital between December 2014 and March 2016.The character in three cases has been studied from several aspects such as clinical presentation, imaging, polysomnography (PSG), cerebrospinal fluid and serum.Results Serum test showed serum contactin-associated protein 2 (CASPR2)antibodies strongly positive (+++) and leucine-rich glioma inactivated protein 1 antibodies positive (+) in three patients.Neuropsychiatric features, neuromyotonia, neuropathic pain, dysautonomia, agrypnia excitata presented in all three patients.The agrypnia excitata was characterized by severe insomnia, excessive motor activity during the night.Agrypnia excitata was diagnosed in three patients according to their history.PSG was finished in case 2 and case 3.PSG in one patient (case 2) documented severe insomnia (sleep efficiency was 59%), lack of cyclic sleep organization with a predominance of stage 1 non-rapid eye movement sleep episodes intermixed with brief rapid eye movement, and a marked reduction of spindles and delta sleep;PSG in another patient (case 3) revealed complete absence of recognizable sleep.Sleep disorders and other symptoms resolved completely or almost completely in two patients (case 1,case 2) who received immunotherapy.Case 3 died from sudden cardiac death before immunotherapy.Conclusions Morvan syndrome usually is associated with high-titer CASPR2 antibodies in serum.Agrypnia excitata is cardinal manifestation of Morvan syndrome in association with a spectrum of neurologic presentations.Early immunotherapy could provide a favorable outcome.

Objective To identify the spectrum of sleep disorders in the patients diagnosed with limbic encephalitis associated with anti leucine rich glioma inactivated protein 1 (LGI1) antibody.Methods Thirteen patients were identified with limbic encephalitis associated with LGI1 antibody in the Department of Neurology,Peking Union Medical College Hospital between December 2012 and August 2017.The characters of the 13 cases were studied from several aspects such as clinical presentation,imaging,polysomnography,cerebrospinal fluid and serum.Results Serum test and/or cerebrospinal fluid test showed LGI1 antibody positive in all the 13 patients.Clinical presentation included:cognitive impairment,seizures,neuropsychiatric features.Sleep disorders presented in all patients,including insomnia,dream enactment behaviors,hypersomnia,involuntary movement.Polysomnogram in the 13 patients revealed that sleep efficiency decreased in 10 patients (＜ 80％),N3 sleep decreased in 10 patients,rapid eye movement sleep decreased in 13 patients;period limb movement disorder was identified in seven patients,period limb movement index was 15.6-224.4/h,four of the seven patients also had frequent irregular motor activity;six patients had frequent faciobrachial dystonic seizures (20-83 times throughout the night);rapid eye movement sleep behavior disorder (RBD) was diagnosed in three patients.Sleep disorder resolved almost completely in 10 of 13 patients who received immunotherapy.Conclusions Sleep disorders are cardinal manifestations of limbic encephalitis associated with LGI1 antibody,including insomnia,RBD,hypersomnia,involuntary movement.They may respond favorably to immunotherapy.

OBJECTIVETo study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma.

METHODSMelanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression.

RESULTSIn melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity. However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector.

CONCLUSIONSBased on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.

Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Humans ; MAP Kinase Signaling System ; Melanoma ; genetics ; metabolism ; Mutation ; Phenotype ; Protein-Serine-Threonine Kinases ; metabolism ; Protein-Tyrosine Kinases ; metabolism ; Proto-Oncogene Proteins B-raf ; metabolism ; Signal Transduction ; Transfection

Objective: To investigate the function and mechanism of zinc finger protein 750 (ZNF750) in esophageal squamous cell carcinoma (ESCC). Methods: Xenograft in nude mice was applied to detect the tumorigenesis of ZNF750-depleted ESCC cells. Western blot was performed to observe the expression of downstream target protein of ZNF750 in ESCC cell lines and xenograft tumor tissues in which ZNF750 was knocked down. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay was used to determine the proliferation of ZNF750 stably depleted cells after restoration of its target protein. Results: The tumor weight of blank control, negative control and ZNF750 knockdown groups was 137±26 mg, 161±31 mg and 463±89 mg, respectively, with a statistically significant difference (P<0.01). The expressions of Kruppel-like factor 4 (KLF4) in ZNF750-depleted ESCC cells and its derived tumor tissue xenograft in nude mice were significantly down-regulated. Restoration of KLF4 in ZNF750 stably depleted cells significantly inhibited the cell proliferation (P<0.01). Conclusions ZNF750 may be a new tumor suppressor in the tumorigenesis of ESCC, and the inhibition of cell proliferation induced by ZNF750 may be partially through the regulation of KLF4 expression.