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Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy： A Randomized Controlled Trial

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Chinese Medical Journal 2016年第16期129卷 1894-1903页

作者： Jie Wu Shu-Wei Duan Xue-Feng Sun Wen-Ge Li Ya-Ping Wang Wen-Hu Liu Jian-Rong Zhang Li-De Lun Xue-Mei Li Chun-Hua Zhou Ji-Jun Li Shu-Wen Liu Yuan-Sheng Xie Guang-Yan Cai Lu Ma Wen Huang Hua Wu Qiang Jia Xiang-Mei Chen Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases Beijing 100853 China Department of Nephrology China-Japan Friendship Hospital Beijing 100029 China Department of Nephrology PLA Army General Hospital Beijing 100700 China Department of Nephrology Beijing Friendship Hospital Capital Medical University Beijing 100050 China Department of Nephrology General Hospital of Chinese People's Armed Police Forces Beijing 100039 China Department of Nephrology Air Force General Hospital of People's Liberation Army Beijing 100142 China Department of Nephrology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China Department of Nephrology Navy General Hospital Beijing 100048 China Department of Nephrology First Affiliated Hospital of General Hospital of People's Liberation Army Beijing 100048 China Treatment center for kidney disease No. 281 Hospital of Beijing Military Region Qinhuangdao Hebei 066100 China Department of Nephrology Beijing Tongren Hospital Capital Medical University Beijing 100730 China Department of Nephrology Beijing Hospital Beijing 100730 China Department of Nephrology Xuanwu Hospital Capital Medical University Beijing 100053 China

Background： The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy （IgAN） are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods： It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan （80 mg/d） wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo （Group A）, 50 mg/d clopidogrel （Group B）, 20 mg/d leflunomide （Group C）, or 50 mg/d clopidogrel and 20 mg/d leflunomide （Group D）. The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese clinical Trial Registry. Results： The effects oftelmisartan combined with leflunomide on changes in proteinuria （0.36 [95% confidence interval （CI） 0.18 0.55] g/d, P 〈 0.001）, in serum uric acid （76.96 [95% CI 57.44-96.49] μmol/L, P 〈 0.001）, in serum creatinine （9.49 [95% CI 6.54-12.44]μmol/L, P 〈 0.001）, and in estimated glomerular filtration rate （-6.72 [95% CI-9.46 to -3.98] *** -1. 1.73 m -2, p 〈 0.001） were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight （P 〉 0.05）.Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions： Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.

关键词： Clopidogrel Immunoglobulin A Nephropathy Leflunomide Randomized Controlled Trial

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Imaging Features of Symptomatic Radiation-induced Cervical Artery Stenosis

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Chinese Medical Journal 2017年第15期130卷 1876-1877页

作者： Jia-Ping Xu Ji-Jun Shi Guang-Xin Duan Yong-Jun Cao Department of Neurology The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215000 China

Recently,the survival rate of head and neck cancer patients has increased with the improvement of radiotherapy （RT） technology and comprehensive *** survivors after RT are at increased risk for cerebrovascular events. Radiation-induced cervical artery stenosis （RICAS） has its own characteristics compared with those lesions without a history of RT.

关键词： Atherosclerosis Cervical Artery Stenosis Imaging Features Radiotherapy

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Integrated analysis of gut microbiome and host immune responses in COVID-19

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Frontiers of Medicine 2022年第2期16卷 263-275页

作者： Xiaoguang Xu Wei Zhang Mingquan Guo Chenlu Xiao Ziyu Fu Shuting Yu Lu Jiang Shengyue Wang Yun Ling Feng Liu Yun Tan Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School ofMedicineShanghai 200025China Schoolof Life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Shanghai Public Health clinical center Shanghai 201508China Department of Laboratory Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious ***,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control *** found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate *** identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia ntuciniphila,Bacteroides cellulosilyticus and Blautia *** further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3^(+)/CD4^(+)/CD8^(+)lymphocyte *** addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low ***,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical ***,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词： COVID-19 SARS-COV-2 gut microbiome immune response

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Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland

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Frontiers of Medicine 2023年第4期17卷 758-767页

作者： Gang Lu Yun Ling Minghao Jiang Yun Tan Dong Wei Lu Jiang Shuting Yu Fangying Jiang Shuai Wang Yao Dai Jinzeng Wang Geng Wu Xinxin Zhang Guoyu Meng Shengyue Wang Feng Liu Xiaohong Fan Saijuan Chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Public Health clinical center Fudan UniversityShanghai 200083China Department of Infectious diseases Research Laboratory of Clinical VirologyNational Research Center for Translational MedicineRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of Microbial Metabolism School of Life Sciences and BiotechnologyThe Joint International Research Laboratory of Metabolic and Developmental SciencesShanghai Jiao Tong UniversityShanghai 200240China

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese *** we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai,identifying a large number of sublineages of the SARS-CoV-2 Omicron *** analysis,coupled with contact history tracing,revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China(BA.5.2 mainly in Guangzhou and Shanghai,and BF.7 mainly in Beijing)and two highly infectious sublineages recently imported from abroad(XBB and BQ.1).Publicly available data from August 31 to November 29,2022 indicated an overall severe/critical case rate of 0.035%nationwide,while analysis of 5706 symptomatic patients treated at the Shanghai Public Health center between September 1 and December 26,2022 showed that 20 cases(0.35%)without comorbidities progressed into severe/critical conditions and 153 cases(2.68%)with COVID-19-exacerbated comorbidities progressed into severe/critical *** observations shall alert healthcare providers to place more resources for the treatment of severe/critical ***,mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year,whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023,and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival(January 21,2023).Altogether,these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population,especially in the rural areas,to ensure the country’s smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

关键词： SARS-CoV-2 COVID-19 Omicron genomic epidemiology

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Epigenetic drug library screening reveals targeting DOT1L abrogates NAD^(+)synthesis by reprogramming H3K79 methylation in uveal melanoma

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Journal of Pharmaceutical Analysis 2023年第1期13卷 24-38页

作者： Xiang Gu Yu Hua Jie Yu Ludi Yang Shengfang Ge Renbing Jia Peiwei Chai Ai Zhuang Xianqun Fan Department of Ophthalmology Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China

Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in *** histone methylation contributes to the abnormal transcriptome during ***,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains ***,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk ***,a systematic epi-drug library screening revealed that DOT1L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in *** Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its ***,NAPRT served as an oncogenic accelerator by enhancing nicotinamide adenine dinucleotide(NAD^(+))***,DOT1L inhibition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of ***,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.

关键词： Histone methylation Metabolic reprogramming Uveal melanoma Transcriptional addiction

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Excessive Daytime Sleepiness in Parkinson＇s disease： clinical Implications and Management

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Chinese Medical Journal 2018年第8期131卷 974-981页

作者： Yun Shen Jun-Ying Huang Jie Li Chun-Feng Liu Department of Neurology and Suzhou clinical research center of Neurological disease The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China Jiangsu Key Laboratory of Neuropsychiatric diseases and Institute of Neuroscience Soochow University Suzhou Jiangsu 215123 China

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 *** 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 ***：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 ***：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.

关键词： Excessive Daytime Sleepiness Parkinson's disease Sleep Disorders

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

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Chinese Medical Journal 2018年第8期131卷 899-906页

作者： Jun-Ying Huang Jin-Ru Zhang Yun Shen Hui-Jun Zhang Yu-Lan Cao Cheng-Jie Mao Ya-Ping Yang Jing Chen Chun-Feng Liu Jie Li Department of Neurology and Suzhou clinical research center of Neurological disease The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China Jiangsu Key Laboratory of Neuropsychiatric diseases and Institute of Neuroscience Soochow University Suzhou Jiangsu 215123 China

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 ***：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 ***：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 ***：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.

关键词： Cognitive Dysfunction Sleep Apnea, Obstructive Parkinson's disease Rapid Eye Movement Sleep Behavior Disorder

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

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Chinese Medical Journal 2018年第8期131卷 907-911页

作者： Kang-Ping Xiong Yong-Ping Dai Jing Chen Jin-Min Xu Yi Wang Ping Feng Shou-Jiang You Chun-Feng Liu Department of Neurology and Suzhou clinical research center of Neurological disease The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China Jiangsu Key Laboratory of Neuropsychiatric diseases and Institute of Neuroscience Soochow University Suzhou Jiangsu 215123 China clinical Laboratory The Second Affiliated Hospital of Soochow University Suzhou JLangsu 215004 China

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 ***：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 ***：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 Cy

关键词： Cystatin C Early Parkinson's disease Objective Sleep Disturbance

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基于CRISPR/Cas12a的可视荧光法快速灵敏检测新型冠状病毒

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Science Bulletin 2020年第17期65卷 1436-1439,M0003页

作者：王鑫杰钟名天刘勇马培祥党露孟庆洲万闻蔚马晓冬刘佳杨光杨子峰黄行许刘明 Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai 201210China Institute for Brain research and Rehabilitation Guangdong Key Laboratory of Mental Health and Cognitive ScienceCenter for Studies of Psychological ApplicationSouth China Normal UniversityGuangzhou 510631China State Key Laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China Kingmed Virology Diagnostic&Translational center Guangzhou Kingmed Center for Clinical Laboratory Co.Ltd.Guangzhou 510005China Affiliated Cancer Hospital&Institute of Guangzhou Medical University Guangzhou 510095China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

新型冠状病毒肺炎(COVID-19)疫情在世界范围爆发,严重危害人类健康,并对公共卫生安全造成重大影响.致病病原体SARS-CoV-2的早期快速准确检测,对及时的隔离防护、诊断治疗、有效控制疫情至关重要.为提供快速便捷的COVID-19诊断方法,本文... 详细信息

新型冠状病毒肺炎(COVID-19)疫情在世界范围爆发,严重危害人类健康,并对公共卫生安全造成重大影响.致病病原体SARS-CoV-2的早期快速准确检测,对及时的隔离防护、诊断治疗、有效控制疫情至关重要.为提供快速便捷的COVID-19诊断方法,本文开发了一种基于CRISPR/Cas12a的可视荧光法检测方案,命名为CRISPR/***/Cas12a-NER无需特殊检测设备,能够在45分钟内获得病例样本的检测结果;并能有效检测到10个病毒拷贝模板数,检测结果与传统qPCR检测结果有很好的一致性.因此, CRISPR/Cas12a-NER提供了一种适用于社区医院或现场检测简单可靠的诊断方法.

关键词：公共卫生安全控制疫情隔离防护灵敏检测荧光法致病病原体社区医院诊断方法

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Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson＇s disease

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Chinese Medical Journal 2017年第9期130卷 1085-1092页

作者： Si-Yue Li Ya-Li Wang Wen-Wen Liu Dong-Jun Lyu Fen Wang Cheng-Jie Mao Ya-Ping Yang U-Fang Hu Chun-Feng Liu Department of Neurology and Suzhou clinical research center of Neurological disease The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China Institute of Neuroscience Soochow University Suzhou Jiangsu 215123 China

Background： Parkinson＇s disease （PD） patients with long-term levodopa （L-DOPA） treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD. Methods： The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine （6-OHDA）, followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days. Rotarod test, footprint test, and open-field test were carried out to evaluate the motor function. Striatum, suprachiasmatic nucleus （SCN）, liver, and plasma were collected at 6：00, 12：00, 18：00, and 24：00. Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes. Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin. High-performance liquid chromatography was used to measure the neurotransmitters. Analysis of variance was used for data analysis. Results： L-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test （P 〈 0.01, P 〈 0.001, respectively）. After L-DOPA treatment, Bmall decreased in the SCN compared with 6-OHDA group at 12：00 （P 〈 0.01） and 24：00 （P 〈 0.001 ）. In the striatum, the expression ofBmall, Rorα was lower than that in the 6-OHDA group at 18：00 （P 〈 0.05） and L-DOPA seemed to delay the peak of Per2 to 24：00. In liver, L-DOPA did not affect the rhythmicity and expression of these clock genes （P 〉 0.05）. In addition, the cortisol secretion was increased （P 〉 0.05）, but melatonin was further inhibited after L-DOPA treatment at 6：00 （P 〈 0.01）. Conclusions： In the circadian system of advanced PD rat models, circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further

关键词： Circadian Rhythm Levodopa Oxidopamine Parkinson disease

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