Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Early changes in white blood cell,C-reactive protein and procalcitonin levels in children with severe multiple trauma

BACKGROUND:To analyze early changes in white blood cells(WBCs),C-reactive protein(CRP)and procalcitonin(PCT)in children with multiple trauma,before secondary inflammation develops.METHODS:This single-center retrospective study collected data from patients with blunt traumatic injury admitted to the pediatric intensive care unit(PICU).According to the prognostic outcome of 28 d after admission to the PICU,patients were divided into survival group(n=141)and non-survival group(n=36).Characteristics between the two groups were compared.Receiver operation characteristic(ROC)curve analysis was conducted to evaluate the capacity of different biomarkers as predictors of mortality.RESULTS:The percentages of children with elevated WBC,CRP,and PCT levels were 81.36%,31.07%,and 95.48%,respectively.Patients in the non-survival group presented a statistically significantly higher injury severity score(ISS)than those in the survival group:37.17±16.11 vs.22.23±11.24(t=6.47,P<0.01).WBCs were also higher in non-survival group than in the survival group([18.70±8.42]×109/L vs.[15.89±6.98]×109/L,t=2.065,P=0.040).There was no significant difference between the survival and non-survival groups in PCT or CRP.The areas under the ROC curves of PCT,WBC and ISS for predicting 28-day mortality were 0.548(P=0.376),0.607(P=0.047)and 0.799(P<0.01),respectively.CONCLUSIONS:Secondary to multiple trauma,PCT levels increased in more patients,even if their WBC and CRP levels remained unchanged.However,early rising WBC and ISS were superior to PCT at predicting the mortality of multiple trauma patients in the PICU.

改良骶前间隙引流途径在腹腔镜超低位直肠癌根治保肛术后吻合口瘘中的应用

目的探讨经改良骶前间隙引流途径冲洗腹腔镜超低位直肠癌根治保肛术后吻合口瘘(AL)的临床应用疗效。方法回顾性分析2008 年1 月—2018 年8 月西南医科大学附属医院收治的33 例行腹腔镜超低位直肠癌根治保肛术后吻合口瘘患者的临床资料,根据引流管拔出途径将吻合口瘘患者分为17 例传统途径组(传统组)和16 例改良途径组(改良组)。传统途径组引流管由骶前间隙路径腹腔拔出,改良途径组引流管经坐骨结节与尾骨连线中点外侧、距肛缘约2.0 cm 处拖出。对比分析两组疗效、并发症发生情况。结果改良组腹膜炎和腹腔积液发生率低于传统组(P <0.05),患者平均住院时间和引流管拔出时间亦均短于传统组(P <0.05)。结论经改良骶前间隙引流途径冲洗超低位直肠癌吻合口瘘应用安全,减少AL 伴发的并发症,缩短住院和冲洗引流时间,此改良途径更适合腹腔镜超低位直肠癌根治保肛术,值得在临床中推广与使用。

Multiple stress fractures of unilateral femur:A case report

BACKGROUND Stress fractures of the femoral neck are not common in clinical practice,and simultaneous stress fractures of the femoral neck and proximal femur of the unilateral femur are even more rare.We introduce a case of this type of fracture that was treated in our department,analyze the causes,and review similar stress fractures reported in the literature to provide references for the diagnosis and treatment of such conditions.CASE SUMMARY A 62-year-old female,with a free medical history,was admitted to the hospital mainly due to pain in the right hip and worsening pain in the right thigh.The patient had no obvious history of trauma.X-ray and computed tomography showed fracture of the femoral neck and proximal femur.The patient had undergone surgery 1 year prior to address a fracture of the left proximal femur that had occurred in a traffic accident.Our first consideration was stress fracture of the femoral neck;however,simultaneous stress fractures of the femoral neck and proximal femur of the unilateral femur were seen.The femoral neck stress fracture was a tension fracture,with obvious displacement and varus deformity of the hip.Considering that the patient was an elderly female,we performed total hip arthroplasty.Follow-up X-rays showed that the stress fracture of the proximal femur had mostly healed after 3 mo.CONCLUSION Muscle fatigue and hip varus deformity provide an anatomical basis for the occurrence of femoral neck stress fractures.

Relationship Between Short-chain Fatty Acids and Parkinson’s Disease:A Review from Pathology to Clinic

Parkinson’s disease(PD)is a complicated neurodegenerative disease,characterized by the accumulation ofα-synuclein(α-syn)in Lewy bodies and neurites,and massive loss of midbrain dopamine neurons.Increasing evidence suggests that gut microbiota and microbial metabolites are involved in the development of PD.Among these,short-chain fatty acids(SCFAs),the most abundant microbial metabolites,have been proven to play a key role in brain-gut communication.In this review,we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor symptoms.Future research should focus on further elucidating the role of SCFAs in neuroinflammation,as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

Management Recommendations on Sleep Disturbance o Patients with Parkinson's Disease

INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sleep disturbance ranges from 47.66% to 89.10%. Sleep disturbance usually has adverse impact on the quality of life of PD patients. Apossible pathogenesis of PD with sleep disturbance include thalamocortical pathway degeneration and changes of neurotransmitter systems. The etiology of sleep disturbance is multifactorial,involving degeneration of areas regulating sleep,sleep structure affected by drugs,sleep disturbance induced by drug,and sleep fragmentation by multiple factors.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition)

Background Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treat-ments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. Methods National Health Commission of China assembled an expert committee for a revision of the guidelines. The com-mittee included 33 members who are specialized in diagnosis and treatment of HFMD. Results Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia;(2) involvement of nervous system;(3) worsening respiratory rate and rhythm;(4) circulatory dysfunction;(5) elevated peripheral WBC count;(6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. Conclusion The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Chinese guidelines for the assessment and provision of nutrition support therapy in critically ill children

Background This document represents the first evidence-based guidelines to describe best practices in nutrition therapy in critically ill children (>1 month and <18 years), who are expected to require a length of stay more than 2 or 3 days in a Pediatric Intensive Care Unit admitting medical patients domain. Methods A total of 25,673 articles were scanned for relevance. After careful review, 88 studies appeared to answer the pre-identified questions for the guidelines. We used the grading of recommendations, assessment, development and evaluation criteria to adjust the evidence grade based on the quality of design and execution of each study. Results The guidelines emphasise the importance of nutritional assessment, particularly the detection of malnourished patients. Indirect calorimetry (IC) is recommended to estimate energy expenditure and there is a creative value in energy expenditure, 50 kcal/kg/day for children aged 1–8 years during acute phase if IC is unfeasible. Enteral nutrition (EN) and early enteral nutrition remain the preferred routes for nutrient delivery. A minimum protein intake of 1.5 g/kg/day is sug-gested for this patient population. The role of supplemental parenteral nutrition (PN) has been highlighted in patients with low nutritional risk, and a delayed approach appears to be beneficial in this group of patients. Immune-enhancing cannot be currently recommended neither in EN nor PN. Conclusion Overall, the pediatric critically ill population is heterogeneous, and an individualized nutrition support with the aim of improving clinical outcomes is necessary and important.

Transcranial Sonographic Alterations of Substantia Nigra and Third Ventricle in Parkinson＆#39;s Disease with or without Dementia

Background： Numerous studies have demonstrated that patients with Parkinson＆#39;s disease （PD） have a higher prevalence of substantia nigra （SN） hyperechogenicity compared with controls. Our aim was to explore the neuroimaging characteristics of transcranial sonography （TCS） of patients with PD and those with PD with dementia （PDD）. The correlation between the echogenicity of the SN and clinical symptoms in Chinese patients with PDD was also assessed. Methods： The ratios of SN hyperechogenicity （SN＋）, maximum sizes of SN＋, and widths of third ventricle （TV） were measured using TCS for all the recruited patients. Data were analyzed using one-way analysis of variance, rank-sum test, Chi-square test, and receiver-operating characteristic （ROC） curve analysis. Results： The final statistical analysis included 46 PDD patients, 52 PD patients, and 40 controls. There were no significant differences in ratios of SN＋ and maximum sizes of SN＋ between PDD and PD groups （P 〉 0.05）. TV widths were significantly larger in PDD group （7.1± 1.9 mm） than in PD group （6.0± 2.0 mm） and controls （5.9 ± 1.5 mm, P 〈 0.05）; however, the ratios of enlarged TV did not differ among the three groups （P = 0.059）. When cutoff value was set at 6.8 mm, the TV width had a relatively high sensitivity and specificity in discriminating between PDD and PD groups （P = 0.030） and between PDD group and controls （P = 0.003）, based on ROC curve analysis. In PDD patients, SN＋ was more frequently detected in akinetic-rigid subgroup, and patients with SN＋ showed significantly higher Hoehn and Yahr stage and Nonmotor Symptoms Questionnaire scores （P 〈 0.05）. Conclusions： Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.

Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson＇s Disease Patients

Background：Rapid eye movement （REM） sleep behavior disorder （RBD） and obstructive sleep apnea （OSA） are the most common sleep disorders in Parkinson’s disease （PD）. The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.Methods：From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography （PSG）. We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.Results：We grouped participants as follows： PD only （n = 53）, PD ＋ OSA （n = 29）, PD ＋ RBD （n = 61）, and PD ＋ RBD ＋ OSA （n = 31）. Minimum oxygen saturation （SaO2） during whole sleep and in REM sleep was higher in PD ＋ RBD ＋ OSA patients than that in PD ＋ OSA patients. PD ＋ RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment （MoCA） scores than those in the PD group （P 〈 0.001）, especially in visuospatial/executive, attention, and memory functions. The PD ＋ OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA （β = ？0.736, P = 0.043） and RBD （β = ？2.575, P 〈 0.001）. The severity of RBD （tonic/phasic electromyography activity） and OSA （apnea-hypopnea index/oxygen desaturation index/minimum SaO2） were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.Conclusions：We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.

Sepsis heterogeneity

Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with extremely high mortality.Notably,sepsis is a heterogeneous syndrome characterized by a vast,multidimensional array of clinical and biologic features,which has hindered advances in the therapeutic field beyond the current standards.Data sources We used PubMed to search the subject-related medical literature by searching for the following single and/or combination keywords:sepsis,heterogeneity,personalized treatment,host response,infection,epidemiology,mortality,incidence,age,children,sex,comorbidities,gene susceptibility,infection sites,bacteria,fungi,virus,host response,organ dysfunction and management.Results We found that host factors(age,biological sex,comorbidities,and genetics),infection etiology,host response dysregulation and multiple organ dysfunctions can all result in different disease manifestations,progression,and response to treatment,which make it difficult to effectively treat and manage sepsis patients.Conclusions Herein,we have summarized contributing factors to sepsis heterogeneity,including host factors,infection etiology,host response dysregulation,and multiple organ dysfunctions,from the key elements of pathogenesis of sepsis.An in-depth understanding of the factors that contribute to the heterogeneity of sepsis will help clinicians understand the complexity of sepsis and enable researchers to conduct more personalized clinical studies for homogenous patients.

Increased Serum Cystatin C in Early Parkinson’s Disease with Objective Sleep Disturbances

Background：Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson’s disease （PD） patients. Cystatin C （CysC） is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.Methods：We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.Results：The mean serum level of CysC was significantly higher in patients with early PD （1.03 ± 0.19 mg/L） compared to controls （0.96 ± 0.15 mg/L, P = 0.009）. There were significantly positive correlations between serum CysC levels and age （r = 0.334, P 〈 0.001）, gender （r = 0.264, P = 0.013）, and creatinine levels （r = 0.302, P = 0.018） in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index （AHI） （r = 0.231, P = 0.017）, especially hypopnea index （r = 0.333, P 〈 0.001）. In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index （r = 0.223, P = 0.021）, percentage of time spent at oxygen saturation （SaO2） 〈90% （r = 0.644, P 〈 0.001）, arousal with respiratory event during sleep （r = 0.247, P = 0.013）. On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO2 （r = ？0.323, ？0.315, both P = 0.001） in PD patients.Conclusions：The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Excessive Daytime Sleepiness in Parkinson＇s Disease： Clinical Implications and Management

Objective：Excessive daytime sleepiness （EDS） is one of the most common sleep abnormalities in patients with Parkinson’s disease （PD）, yet its multifactorial etiology complicates its treatment. This review summarized recent studies on the epidemiology, etiology, clinical implications, associated features, and evaluation of EDS in PD. The efficacy of pharmacologic and non-pharmacologic treatments for EDS in PD was also reviewed.Data Sources：English language articles indexed in PubMed and Cochrane databases and Chinese-language papers indexed in Wanfang and National Knowledge Infrastructure databases that were published between January 1987 and November 2017 were located using the following search terms： ＂sleepiness＂ , ＂sleep and Parkinson’s disease＂ , and ＂Parkinson’s disease and treatment＂ .Study Selection：Original research articles and critical reviews related to EDS in PD were selected.Results：EDS is a major health hazard and is associated with many motor and nonmotor symptoms of PD. Its causes are multifactorial. There are few specific guidelines for the treatment of EDS in PD. It is first necessary to identify and treat any possible factors causing EDS. Recent studies showed that some nonpharmacologic （i.e., cognitive behavioral therapy, light therapy, and repetitive transcranial magnetic stimulation） and pharmacologic （i.e., modafinil, methylphenidate, caffeine, istradefylline, sodium oxybate, and atomoxetine） treatments may be effective in treating EDS in PD.Conclusions：EDS is common in the PD population and can have an immensely negative impact on quality of life. Its causes are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential therapies and to develop novel treatment approaches for EDS in PD.

Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in China's Mainland

Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The present survey was to investigate the prevalence rate of wearing-off(WO)and dyskinesia among the patients with PD in China.Methods:From May 2012 to October 2012,a 3-step registry survey for wearing off(WO)and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.Results:There were 1,558 PD patients fulfilling the inclusion criteria.Among them,1,051 had at least one positive response of 9-item wearing off questionnaire(WOQ-9),724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists,respectively.The overall prevalence rates of WO and dyskinesia were 46.5%(95%CI 44.0%-48.9%)and 10.3%(95%CI 8.8%-11.8%),respectively.The mean score of WOQ-9 for those with WO was 3.8(SD=1.8),with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms.Better improvement of motor symptoms(n=354,87.8%)and long-term disease control and drug selection(n=288,71.5%)were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.Conclusions:This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from China's Mainland.WO prevalence rate among Chinese PD patients was in line with,while dyskinesia prevalence rate was lower than previous reports from other Countries.

A New Perspective for Parkinson's Disease:Circadian Rhythm

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei （SCN） in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson＇s disease （PD） exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative conse- quences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria

Background Parkinson’s disease(PD)is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic(DA)neurons in the substantia nigra region of the brain.Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfoldedα-synuclein aggregations.Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD.However,there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function.In addition,the half-life of mitochondria varies between days to a few weeks.Thus,identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes.In this study,we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD.Methods We generated DA neurons and astrocytes from human iPSCs and hESCs.We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer,as well as the neuroprotective effect of mitochondrial transfer.We employed immunocytochemistry and FACS analysis to track mitochondria.Results We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media(ACM)can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model.Specifically,we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media.Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway.Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone.When rotenone injured neurons were cultured in presence of ACM depleted of mitochondria(by ultrafiltration),the neuroprotective effects were abolished.Conclusions Our studies provide the proof of principle that iPSCs-derived astrocytes can act as mitochondria donor to the injured DA neurons and attenuate pathology.Using iPSCs derived astrocytes as a donor can provide a novel strategy that can be further developed for cellular therapy for PD.

Tonic Electromyogram Density in Multiple System Atrophy with Predominant Parkinsonism and Parkinson＇s Disease

Background： Both Parkinson＇s disease （PD） and multiple system atrophy （MSA） have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism （MSA-P） resembles PD in the manifestation of prominent parkinsonism, Whether the amount of rapid eye movement （REM） sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods： This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder （RBD） prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram （EMG） activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results： No significant difference between MSA-P group and PD group had been tbund in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index （AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024） and higher tonic chin EMG density （34.02 [ 18.48, 57.18]% vs. 8.40 [3.11, 13.061%, P 〈 0.001 ） as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA ＋ RBD subgroup was higher than that in PD ＋ RBD subgroup （55.04 [26.81,69.62]% vs. 11.40 [8.51,20.411%, P 〈 0.001 ）. Furthermore, no evidence of any difference in tonic EMG density emerged between PD ＋ RBD and MSA - RBD subgroups （P 〉 0.05）. Both disease duration （P = 0.056） and AHI （P = 0.051） showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD ＋ RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P （[3 0.552, P 〈 0.001 ） and RBD （[3 = 0.433, P 〈 0.001 ） as predictors of higher tonic EMG density. Conclusion： Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.

Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson＆#39;s Disease

Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment.The aim of this study was： （1） to investigate the domains of cognitive impairment in patients with PD and RBD, and （2） to explore risk factors for PD-mild cognitive impairment （PD-MCI） and the relationship between RBD severity and impairment in different cognitive domains in PD.Methods： The participants were grouped as follows： PD without RBD （PD-RBD;n =42）, PD with RBD （PD ＋ RBD;n =32）, idiopathic RBD （iRBD;n =15）, and healthy controls （HCs;n =36）.All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function.The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD ＋ RBD groups.Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong （RBDQ-HK） and the RBD Screening Questionnaire （RBDSQ）, then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Results： Compared to PD-RBD subjects, PD ＋ RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher （P 〈 0.05）.During neuropsychological testing, PD ＋ RBD patients performed worse than PD-RBD patients, including delayed memory function, especially.The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD ＋ RBD, iRBD, and HC groups, respectively.RBD was an important factor for the PD-MCI variance （odds ratio =5.204, P =0.018）.During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B （errors） and Auditory Verbal Learning Test （delayed recall） and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure （copy） results.Conclusions： When PD-RBD and PD ＋ RBD patients have equivalent motor symptoms, PD ＋ RBD patients still have more olfactory dysfunction and worse daytime somnolence.RBD is an important risk factor for MCI, including delayed memory.Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.

Efficacy and safety of intravenous recombinant tissue plasminogen activator in mild ischaemic stroke:a meta-analysis

The benefits and safety of intravenous recombinant tissue plasminogen activator(IV-tPA)for patients with mild ischaemic stroke(MIS)are still unclear.The objective of this meta-analysis was to evaluate the efficacy and safety of IV-tPA as treatment for patients with MIS.We performed a systematic literature search across MEDLINE,Embase,Central,Global Health and Cumulative Index to Nursing and Allied Health Literature(CINAHL),from inception to 10 November 2016,to identify all related studies.Where possible,data were pooled for meta-analysis with odds ratio(OR)and corresponding 95%confidence interval(CI)using the fixed-effects model.MIS was defined as having National Institutes of Health Stroke Scale score of≤6.We included seven studies with a total of 1591 patients based on the prespecified inclusion and exclusion criteria.The meta-analysis indicated a high odds of excellent functional outcome based on the modified Rankin Scale or Oxfordshire Handicap Score 0-1(OR=1.43;95%CI 1.14 to 1.79;P=0.002,I2=35%)in patients treated with IV-tPA compared with those not treated with IV-tPA(74.8%vs 67.6%).There was a high risk of symptomatic intracranial haemorrhage(sICH)with IV-tPA treatment(OR=10.13;95%CI 1.93 to 53.02;P=0.006,I2=0%)(1.9%vs 0.0%)but not mortality(OR=0.78;95%CI 0.43 to 1.43;P=0.43,I2=0%)(2.4%vs 2.9%).Treatment with IV-tPA was associated with better functional outcome but not mortality among patients with MIS,although there was an increased risk of sICH.Randomised trials are warranted to confirm these findings.

Sleep Disorders in Parkinson＇s Disease： Present Status and Future Prospects

INTRODUCTION Parkinson＇s disease （PD） is the second most common neurodegenerative disorder in the world. In China, approximately 48-89% of Chinese patients with PD have been shown to be affected by sleep disorders, in recent decades, there have been major advances in our understanding of the relationship between sleep disorders and PD, yet many questions remain unanswered.