SFTSV nucleoprotein mediates DNA sensor cGAS degradation to suppress cGAS-dependent antiviral responses.

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

Neutralizing antibodies and cellular immune response after two doses of inactivated SARS-CoV-2 vaccine in China.

BACKGROUND: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine. METHODS: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China. RESULTS: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type. CONCLUSION: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

Nanomedicine Strategies for Sustained, Controlled and Targeted Treatment of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most devastating diseases worldwide. The current drugs for AD can only ameliorate the symptoms rather than reverse or prevent the progress of AD. On the other hand, blood-brain barrier (BBB), as a natural barrier, significantly impedes drug delivery from the blood circulation into the brain. Nanomedicine can be a safe, effective and promising approach to treat AD. OBJECTIVE: This review summarizes the recent nanomedicine research in this area, including the use of liposomes and nanoparticles (NPs), to provide new approach for targeted treatment of AD. METHOD: Collecting and referring to the related literature in recent 10 years, via searching MeSH Terms "Alzheimer's disease; nanomedicine; nanoparticle; amyloid ß peptide; tau protein; autophagy". RESULTS: Nanomedicines show superiority over conventional anti-AD drugs as a potential weapon against AD by the five proposed mechanisms: many unfavorable pharmaceutical properties of conventional anti-AD drugs maybe greatly overcome by nanomedicine; nanomedicines trigger efficient production of high-titer anti-Aß antibodies following controlled release of antigens by them; some apolipoprotein- based nanomedicines could preferably bind to Aß and increase the elimination of Aß nanomedicine-induced autophagy could be facilitated to increase the elimination of Aß nanomedicineinduced inhibition of tau aggregation. CONCLUSION: Therefore, nanomedicine-mediated drug therapy is promising in the treatment of AD.

Emergency preparedness for mass gatherings: Lessons of "12.31" stampede in Shanghai Bund.

According to WHO, one of these mass gatherings with critical risk is stampedes. Shanghai "12.31" stampede was a preventable tragedy that the government and event planner hold responsibility for. At the same time, it can be a legacy for improvement in the future. The government should draw experience on the implementation of an emergency preparedness system, in order to improve the rapid emergency response during mass gatherings in the future.

Chronic Sleep Restriction Induces Cognitive Deficits and Cortical Beta-Amyloid Deposition in Mice via BACE1-Antisense Activation.

AIMS: To clarify the correlation between chronic sleep restriction (CSR) and sporadic Alzheimer disease (AD), we determined in wild-type mice the impact of CSR, on cognitive performance, beta-amyloid (Aß) peptides, and its feed-forward regulators regarding AD pathogenesis. METHODS: Sixteen nine-month-old C57BL/6 male mice were equally divided into the CSR and control groups. CSR was achieved by application of a slowly rotating drum for 2 months. The Morris water maze test was used to assess cognitive impairment. The concentrations of Aß peptides, amyloid precursor protein (APP) and ß-secretase 1 (BACE1), and the mRNA levels of BACE1 and BACE1-antisense (BACE1-AS) were measured. RESULTS: Following CSR, impairments of spatial learning and memory consolidation were observed in the mice, accompanied by Aß plaque deposition and an increased Aß concentration in the prefrontal and temporal lobe cortex. CSR also upregulated the ß-secretase-induced cleavage of APP by increasing the protein and mRNA levels of BACE1, particularly the BACE1-AS. CONCLUSIONS: This study shows that a CSR accelerates AD pathogenesis in wild-type mice. An upregulation of the BACE1 pathway appears to participate in both cortical Aß plaque deposition and memory impairment caused by CSR. BACE1-AS is likely activated to initiate a cascade of events that lead to AD pathogenesis. Our study provides, therefore, a molecular mechanism that links CSR to sporadic AD.

An observational clinical and video-polysomnographic study of the effects of rotigotine in sleep disorder in Parkinson's disease.

PURPOSE: Sleep disturbance is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopamine agonists influence nocturnal sleep in PD, particularly in sleep laboratory data to measure sleep parameters and their changes objectively. The goal of this open-label study was to objectively evaluate the effect of rotigotine on sleep in PD patients by video-polysomnographic methods. METHODS: A total of 25 PD patients with complaints of nocturnal sleep impairment were enrolled. The sleep quality before and after stable rotigotine therapy was evaluated subjectively through questionnaire assessments and objectively measured by video-polysomnographic methods. The Parkinsonism, depression, anxiety, and quality of life of PD patients were also evaluated through questionnaire assessments. RESULTS: At the end of rotigotine treatment, the PD daytime functioning, motor performance, depression, subjective quality of sleep, and the quality of life improved. Video-polysomnographic analysis showed that the sleep efficiency and stage N1% were increased, while the sleep latency, wake after sleep onset, and the periodic leg movements in sleep index were decreased after rotigotine treatment. CONCLUSIONS: Video-polysomnographic analysis confirmed the subjective improvement of sleep after rotigotine treatment. This observation suggests that in PD rotigotine is a treatment option for patients complaining from sleep disturbances.

Interleukin-1ß Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1ß and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1ß and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1ß CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1ß TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1ß levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1ß-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1ß-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance.

Rivastigmine Patch in Chinese Patients with Probable Alzheimer's disease: A 24-week, Randomized, Double-Blind Parallel-Group Study Comparing Rivastigmine Patch (9.5 mg/24 h) with Capsule (6 mg Twice Daily).

AIMS: To compare the once-daily rivastigmine patch 9.5 mg/24 h (10 cm(2) ) versus twice-daily capsule (12 mg/day) in Chinese patients with probable Alzheimer's disease (AD) (mini-mental state examination [MMSE] scores of 10-20). METHODS: The primary objective was to demonstrate the noninferiority of patch to capsule in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) change from baseline to 24 week. Secondary endpoints included cognition (MMSE), overall clinical response (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC]), activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]), behavior (Neuropsychiatric Inventory [NPI-12]), and safety. RESULTS: Similar cognitive improvement was observed in both patch (n = 248) and capsule (n = 253) groups. Statistical noninferiority for ADAS-Cog was not established (least-square means difference, 0.1; 95% confidence interval, -1.2; 1.5). Considering all efficacy parameters into account, both treatments showed similar performance at Week 24. Treatment-related adverse events (AEs) were lower for patch (39.7%) compared with capsule (49.8%). Application site pruritus was reported in 10.9% of patients receiving patch; most cases were mild. Gastrointestinal AEs including nausea, vomiting, and diarrhea occurred less frequently in the patch group (15.8% vs. 28.7%). CONCLUSION: Rivastigmine patch 9.5 mg/24 h is effective and well tolerated in Chinese patients with probable AD.

Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

Validation of the rapid eye movement sleep behavior disorder screening questionnaire in China.

We validated the Chinese version of the rapid eye movement sleep behavior disorder (RBD) screening questionnaire (RBDSQ) and calculated its cut-off value for idiopathic or symptomatic sleep behavior disorders (iRBD or sRBD) in Chinese people. Patients with RBD (n=63) and controls (n=165) were enrolled. After all subjects had completed a structured interview, the Chinese version of the RBDSQ and the video polysomnography test, we evaluated the reliability, areas under the curves and the best cut-off values of the RBDSQ and investigated the utility of RBDSQ for iRBD and sRBD in China. We found that Cronbach's alpha was 0.769 and the test-retest reliability was 0.916. RBDSQ scores in iRBD and sRBD patients were similar and higher than those in controls. A total of five points represented the best cut-off value for detecting all RBD patients. In Parkinson's disease, a total score of six points represented the best cut-off value for detecting sRBD. There was no statistically significant difference in total RBDSQ score between iRBD and sRBD, or male and female patients. There was no significant correlation between the RBDSQ score and duration or severity of RBD symptoms. The Chinese version of the RBDSQ had high sensitivity, specificity and reliability and could be used as a tool for screening RBD patients in China.

Cortactin expression confers a more malignant phenotype to gastric cancer SGC-7901 cells.

AIM: To study the effects of cortactin on the tumor biology of SGC-7901 cells and identify the mechanism involved in the process. METHODS: Cell lines in which cortactin was stably overexpressed or knocked down as well as the respective control cell lines were established by standard molecular methods. The effects of cortactin on the proliferation, migration and invasion capacity of SGC-7901 cells were assessed by the MTT assay, colony formation, flow cytometry, transwell migration and matrigel invasion. Nude mouse models were also used to assess the role of cortactin in the growth and metastasis of SGC-7901 cells in vivo. Western blotting analysis was performed to detect the expression of epidermal growth factor receptor (EGFR) and downstream molecules. RESULTS: Cell lines in which cortactin was stably overexpressed or knocked down as well as control cell lines were successfully established and designated as LV5-cortactin-SGC, LV5-SGC, LV3-shRNA-SGC and LV3-SGC. Cortactin overexpression promoted SGC-7901 cell migration (340.7 ±12.6 vs 229.1 ± 23.2, P < 0.01) and invasion (71.6 ± 5.2 vs 48.4 ± 3.6, P < 0.01). Cortactin downregulation impaired SGC-7901 cell migration (136.2 ± 19.8 vs 225 ± 17) and invasion (29.2 ± 5.2 vs 49.6 ± 3.8, P < 0.01). The results from the MTT and colony formation assays results indicated increased LV5-cortactin-SGC cell proliferation and decreased LV3-shRNA-SGC cell proliferation compared to the control cells. Flow cytometry analysis demonstrated that cortactin overexpression promoted the proliferation index of SGC-7901 cells, and the results were reversed when cortactin was downregulated. Mouse tumor models confirmed that cortactin expression increased SGC-7901 cell proliferation and metastasis in vivo. Western blotting analysis revealed that cortactin elevated EGFR expression and activated the downstream molecules. CONCLUSION: Cortactin expression promoted the migration, invasion and proliferation of SGC-7901 cells both in vivo and in vitro. The EGFR signaling pathway is mechanistically involved.

Hypnic headache responsive to sodium ferulate in 2 new cases.

BACKGROUND: Hypnic headache is a rare disorder characterized by frequent nocturnal attacks of a generalized headache in the elderly. METHOD: This is the first report identifying 2 Chinese hypnic headache cases according to its diagnostic criteria. Both of the patients received sodium ferulate (100 or 50 mg, 3 times/d) for 2 or 3 months. RESULTS: The results of polysomnography in our cases indicated the onset of headache attacks in non-rapid eye movement sleep stage 2. Their symptoms were completely relieved for 1 year after the treatment. CONCLUSION: Our results suggest that sodium ferulate could be a potential treatment for hypnic headache.

[Analysis of misdiagnosed cases with benign paroxysmal positional vertigo].

OBJECTIVE: To analyze the misdiagnosed cases with benign paroxysmal positional vertigo (BPPV). METHODS: During October 2010 to January 2011, a total of 287 patients with dizziness visited the Dizziness Clinic at Changzheng Hospital, Second Military Medical University. Forty-eight misdiagnosed cases with BPPV were collected and their clinical data were analyzed. All 48 cases were diagnosed by the Dix-Hallpike or Roll test maneuver. RESULTS: (1) CLINICAL FEATURES: there were 38 females and 10 males with an average age of 54 ± 12 years old (range: 31 - 87). Posterior semicircular canal was involved in 75.0% (36/48) whereas the horizontal semicircular and multiple canals in 20.8% (10/48) and 4.2% (2/48) respectively. All patients were treated successfully. And 41 cases (85.4%) were cured on the first visiting day. Recurrences of BPPV occurred in 6 cases during the follow-up. (2) The initial visiting departments consisted of the department of general internal medicine 43.8% (21/48), department of neurology 27.1% (13/48), department of osteology 18.7% (9/48), ear, nose & throat (ENT) department 2.1% (1/48) and other departments 8.3% (4/48). In addition, 68.7% (33/48) of them frequented the general out-patient clinics during their initial visits and the other 31.3% (15/48) used the emergency services. (3) The initial diagnoses included vertebrobasilar insufficiency/cerebral circulation insufficiency 27.1% (13/48), cervical spondylosis 27.1% (13/48), cerebral infarction 4.2% (2/48), Meniere's disease 2.1% (1/48) and others 10.4% (5/48); Besides, 29.1% (14/48) of them had no diagnosis. (4) The average clinic visits per patient were 3.4 times (164 visits/48 cases). (5) The most commonly performed tests included brain computed tomography (CT) (28 person-times), cervical magnetic resonance imaging (MRI) (19 person-times), brain MRI (18 person-times), cervical radiography (18 person-times) and cervical CT (8 person-times). CONCLUSION: In these misdiagnosed cases of BPPV, most of them were middle-aged women. They were most likely to have their first consultations in the departments of general internal medicine and neurology. Therefore these two departments should pay more attention to applying the maneuver of Dix-Hallpike or Roll test so as to reduce the misdiagnosis of BPPV and the waste of healthcare resources.

A systematic review of clinical outcomes, perioperative data and selective adverse events related to mild hypothermia in intracranial aneurysm surgery.

BACKGROUND: In the last two decades, mild intraoperative hypothermia has become widely accepted as a protective therapy in neurosurgery. However, its effect in intracranial aneurysm surgery remains unclear. OBJECTIVE: The purpose of this study was to assess the perioperative effects and selected adverse events associated with intraoperative mild hypothermia in aneurysm surgery and to compare those with events in normothermic surgery. METHODS: Three literature databases, namely the Cochrane Library, PubMed and EMBASE, were searched for randomised controlled trials (RCTs) of aneurysm surgery that compared intraoperative mild hypothermia and normothermia from January 1965 to August 2010. Three RCTs were identified. We extracted the following information: author names and publication year; clinical outcome (number of deaths and Glasgow outcome scales); perioperative data (number of moderate or severe intraoperative brain swelling occurrences, hypertensive episodes, ruptured or leaking aneurysms, volume of blood loss during surgery, duration of temporary clipping, and number of patients who received protective drugs, who required rewarming and who were intubated); number of adverse events (cerebral infarctions, brain swelling, myocardial ischaemia or infarction, congestive heart failure, meningitis or ventriculitis and pneumonia). Except for author names and publication year, the data were pooled to perform a mean effect size estimate. The effects of intraoperative mild hypothermia were then analysed. RESULTS: The number of patients requiring rewarming in the mild hypothermia group was significantly greater than in the normothermia group (odds ratio, 33.89; 95% confidence intervals, 3.61-318.36). There were no other statistically significant differences. CONCLUSION: Based on available RCTs, especially involving surgery of low-grade aneurysms, intraoperative mild hypothermia showed no advantages compared with normothermia.

Serum level of interleukin-6 in Chinese patients with multiple sclerosis.

The aim of this study was to investigate the serum concentration of interleukin (IL)-6 in patients with relapsing-remitting MS (RR-MS), compare the difference between males and females, and explore the correlation between the serum concentration of IL-6 and clinical parameters like the current age, the age at onset, disease duration, disability (expanded disability status scale, EDSS), and the number of relapse. We compared the serum concentration of IL-6 in 39 patients with MS and 39 healthy controls matched with sex and age. The serum IL-6 concentration was measured by FlowCytomix. Compared to healthy controls, both the frequency of subjects with detectable level of IL-6 (P=0.005) and the serum concentration of IL-6 (P=0.004) were significantly higher in MS patients. When data were analyzed by gender, statistical significances between MS patients and healthy controls were observed only in females, although the frequency with detectable level and the serum concentration of IL-6 were higher in male MS patients than male controls. The serum level of IL-6 was found to be significantly positively correlated with the number of relapse for female MS patients (r(s)=0.511, P=0.009), with the current age for male MS patients (r(s)=0.700, P=0.005), and with the age at onset for all MS patients (r(s)=0.351, P=0.028). Our results may support that IL-6 is involved in the pathogenesis of MS and indicate that differences exist between male and female patients.

Serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with multiple sclerosis.

It has been reported that cytokines play an important role in the pathogenesis of multiple sclerosis (MS). The aim of this study was to evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with MS. We compared the serum concentrations of pro-inflammatory cytokines IL-18, IL-23 and IL-17 in 39 patients with MS and 39 healthy controls matched with sex and age. Serum cytokines were measured by FlowCytomix, a kind of cytometric bead-based assay. Correlations between the serum levels of the three cytokines and disability (expanded disability status scale, EDSS), disease duration, current age and age at onset were examined. Serum concentrations of all IL-18, IL-23 and IL-17 were significantly higher in MS patients than healthy controls. There were no significant differences of the three cytokines' levels between female and male healthy controls, while the serum IL-18 level was observed significantly higher (P=0.049) in male MS patients than female MS patients. No significant correlations were observed between any of the three cytokines' levels and EDSS, disease duration and current age. However, IL-23 was found negatively correlated with age at onset in male MS patients (r(s)=-0.775, P=0.041). Our data suggest that all IL-18, IL-23 and IL-17 may be involved in the pathogenesis of MS. However, the relationships of the three cytokines and clinical characteristics of MS need to be further investigated in the future.

Efficacy and safety of pramipexole in chinese patients with restless legs syndrome: results from a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: We performed a six-week study of pramipexole vs. a placebo in Chinese restless legs syndrome patients. METHODS: Overall, 305 enrolled patients were assigned randomly in a 2:1 ratio to the pramipexole group (N=202) and the placebo group (N=103). RESULTS: Of 287 patients in the full analysis set, the pramipexole group showed significant improvement compared with the placebo group in the change of their International Restless Legs Syndrome Study Group Rating Scale of Severity (IRLS) total score from baseline to week 6 after adjustment of centers and baseline characters (-15.87±0.66 vs. -11.35±0.92, p<0.0001) and in the proportion of patients who were "much improved" and "very much improved" when measured by Clinical Global Impressions-Improvement (81.9% vs. 54.3%, p<0.0001). At week 6, the IRLS responder rate was 73.8% (pramipexole) and 48.9% (placebo) (p<0.0001) and the patient global impression responder rate was 68.6% (pramipexole) and 43.5% (placebo) (p<0.0001). The proportion of adverse events was 62.9% in the pramipexole group and 43.7% in the placebo group, respectively. No deaths occurred. CONCLUSION: Pramipexole was effective and well-tolerated in Chinese patients with restless legs syndrome.