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The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.
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Objective:To detect the changes in mental arithmetic competence and the related influencing factors in patients with early Parkinson's disease(PD)by using mental arithmetic task behavioral experiment.Methods:Thirty-one patients with early PD and 40 healthy controls were enrolled in this study.The cognitive functions were tested by mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA). The differences of mental arithmetic competence between the two groups were measured by behavioral experiment.Results:There was no significant difference in correct rate, reaction time and post-corrected reaction time while performing baseline tasks and easy mental arithmetic tasks between the two groups( P>0.05). The reaction time had no significant difference between the two groups after adjusting some confounding factors( P>0.05). However, the correct rate while performing difficult mental arithmetic tasks was significantly lower( t=-2.232, P=0.029)and the reaction time was significantly longer( t=2.149, P=0.035)in PD group than in the controls, and the significant difference in reaction time persisted even after adjusting some confounding factors( t=3.139, P=0.003). In PD group, the correct rate of difficult mental arithmetic tasks was positively associated with MoCA scores( r=0.561, P=0.004), and negatively associated with age( r=-0.532, P=0.008). The reaction time and post-corrected reaction time while performing difficult metal arithmetic task were negatively associated with MoCA scores( r=-0.525, P=0.01; r=-0.554, P=0.005)and positively associated with age( r=0.485, P=0.037; r=0.514, P=0.012)in PD group. Conclusions:The difficult mental arithmetic competence is impaired in early PD patients, which is statistically significantly correlated with cognitive function and age.
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Objective To investigate the relationship between two single nucleotide polymorphisms (rs356219,rs356165 sites) and cognitive dysfunction in Parkinson disease.Methods 236 patients with Parkinson's disease were randomly selected from November 2014 to November 2017.According to the results of MoCA cognitive function evaluation,the patients were divided into group A (cognitive dysfunction group)and group B (normal cognition group).At the same time,65 patients were randomly selected as group C (Health control group).The allele frequency and genotype distribution of rs356219 and rs356165 were compared,and the differences among the three group were compared.Results In the rs356165 allele frequency,group A (G:57.14％,A:42.86％),group B (G:56.45％,A:43.55％) and group C (G:52.31％,A:47.69％) had no statistical significance (P＞ 0.05).In the rs356165 genotype,G/G (21.43％) and A/A (14.29％) in group A were higher than group C (G/G:4.62％,A/A:1.54％),G/G (22.58％) in group B and A/A (14.52％) were higher than group C G/G (4.62％) and A/A (1.54％) (P＜ 0.05).In the rs356219 allele frequency,group A (G:64.29％,A:64.29％) and group B (G:64.52％,A:35.486％) and group C (G:46.15％,A:53.85％) was statistically significant (P＜0.05),but no statistical significance between group A and group B (P＞0.05);In the rs356219 genotype,group A (G/G:35.71％,A/A:21.43％,A/G:42.86％),group B (G/G:35.48％,A/A:22.58％,A/G:41.94％) and group C (G/G:30.77％,A/A:26.15％,A/G:43.08％) had no statistical significance (P＞ 0.05),and there was no statistical significance between group A and group B (P＞0.05).Conclusions The polymorphism of rs356219 and rs356165 sites in rho-synaptic nucleoprotein plays an important role in the pathogenesis of Parkinson disease.However,there was no correlation with cognitive dysfunction in patients with Parkinson disease.
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Objective: To discuss the therapeutic regimen for warfarin resistant patients with the help of clinical pharmacists. Methods:The pharmacist analyzed the cause of warfarin resistance and provided the dose adjustment for a pulmonary embolism pa-tient. Results:The genotype of the patient was identified as VKORC1-1639AG by gene test. The patient was diagnosed as hereditary warfarin resistance excluding other causes. With the assistance of pharmacist, the problem of warfarin resistant was solved. Conclu-sion:For warfarin resistant patients, clinical pharmacists must definite the reason of warfarin resistant firstly and then carry out the therapeutic strategy. Gene detection may be used as an important guide for warfarin resistance.
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Objective To detect the impairment of response inhibition and working memory in patients with alcohol dependence.Methods A total of forty-eight alcohol dependent patients and fifty age,gender,IQ,education matched controls were recruited.Neuropsychological tests were applied to measure the differences of response inhibition and working memory between the two groups.Results In the response inhibition task,the patient group had more commission errors ((7.02± 3.48) vs (3.45± 1.52)) and longer reaction time ((605.45 ± 142.56)ms vs (435.72±51.18)ms) compared to the control group (t=6.534,P=0.000; t=7.781,P=0.000).In the spacial working memory task,the patient group also had more commission errors ((4.58± 3.45) vs (0.43± 0.88)) and longer reaction time((10566.16±2455.61) ms vs (9185.44±2677.52) ms) than control (t=8.085,P =0.000; t=2.657,P=0.009).Conclusion There are significant deficiencies in response inhibition and working memory in patients with alcohol dependence.
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Objective To investigate the clinical effect of botulinum toxin type A (BTX-A) injections guided by electromyography in combination with electrical stimulation in the treatment of upper limb spasticity poststroke.Methods Forty-five patients with upper limb spasticity following stroke were recruited.They received multiple intra-muscular BTX-A injections guided by electromyography and electrical stimulation.Rehabilitation training was administered after the BTX-A injections.The results were assessed using the modified Ashworth scale (MAS),the Fugl-Meyer upper limb assessment (FMA),active range of movement (AROM) and the modified Barthel index (MBI).All the assessments were performed at the baseline,and then 1 week,2 weeks,1 month,and 3 months after the injections.Results Compared with the baseline scores the MAS,FMA,AROM and MBI results had all obviously improved by 2 weeks after the BTX-A injections.Compared with 2 weeks after the injections,the FMA and AROM scores at 1 month were significantly higher and there were further significant improvements at 3 months.No patient demonstrated obvious side effects from the therapy.Conclusion BTX-A injection guided by electromyography and electrical stimulation is safe and has definite beneficial effects on upper limb spasticity after stroke.
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Objective To investigate the relationship between the cerebral microbleeds (CMBs) and changes of cognitive function,and the possible mechanism of cognitive impairment caused by CMBs.Methods Sixty-eight micro-hemorrhage patients on susceptibility weighted imagine (SWI) sequences composed positive group,and sixty-eight patients selected without micro-hemorrhage in the SWI sequence and meeting the selection criteria as control group.At the same time,both two groups were assessed by MoCA and CDT scale inspection.Results CDT scores of CMBs group (2.00±0.88) were significantly lower than those of control group (3.76±0.53),and there was significantly different in the two groups (t=-3.27,P=0.00).At the same time,MoCA total scores and executive functions,naming,calculation,language,abstraction,recall scores of CMBs group were significantly lower than those of control group,and all of the groups were significantly different (t=-5.48,P=0.00; t=-4.36,P=0.00; t=-2.35,P=0.01 ; t=-2.49,P=0.02; t=-4.09,P=0.00; t=-4.63,P=0.00).CDT scores,MoCA total scores,executive functions,language,abstraction,memory scores between CMBs groups and control group were significantly different at all levels (P＜0.05).Executive functions,languages and calculated inter-group of mild CMBs,moderate CMBs,severe CMBs were significantly different (P＜0.05).The number of CMBs was negative correlation with total scores,executive function,language,and abstract (r=-0.675,P=0.000; r=-0.689,P=0.000; r=-0.536,P=0.000; r=-0.636,P=0.000).Conclusion The existence of CMBs and the number of CMBs are closely related to cognitive dysfunction.The more of CMBs,the more of obvious cognitive impairment.
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ObjectiveTo detect the fiber structure and volume differences in frontal lobe between patients with amnestic mild cognitive impairment (aMCI) and normal control.MethodsT1 -weighted magnetic resonance imaging and diffusion tensor imaging were obtained in 28 aMCI patients and 25 normal controls.Volumes,fiber fractional anisotropy (FA),fiber apparent diffusion coefficient (ADC),fiber number,and average fiber length of frontal lobe in the two groups were measured.ResultsVolumes of left frontal lobe ( ( 337.35 ± 20.45 ) cm3 ) in aMCI group were smaller than control ( (358.54 ± 27.26) cm3 ) ( t =- 3.223,P =0.002 ).Numbers of short range fiber in left frontal lobe ( 16985 ± 892) were significantly increased relative to control ( 16387 ±752) ; while numbers of long range fiber (3214 ± 185 ) were reduced compared with control (3425 ± 277 ),and ADC values increased ( t =2.621,P =0.012; t =-3.714,P =0.001 ; t =17.595,P=0.000).In aM CI group,numbers of long range fiber in right frontal lobe were reduced (2895 ± 343 vs.3451 -± 230,t =- 7.011,P =0.000),and ADC values were increased ( t =4.443,P =0.000).In aMCI group,numbers of long range fiber in left frontal lobe were positively correlated with scores of mini-mental state examination ( MMSE ) ( r =0.457,P =0.015 ),while ADC values of long range fiber in left frontal lobe were negatively correlated with scores of MMSE ( r=-0.415,P=0.028).ConclusionThe structure and fiber connectivity are affected in aMCI patients and the lesion of connectivity in left frontal lobe are related to the severity of symptom.
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[Objective]To establish a novel noninvasive fluorescent animal model for endometriosis in vitro and in vivo.[Methods]Adenovirus encoding enhancing green fluorescent protein(Ad-eGFP)was used to transfect endometrial glandular cells and stromal cells(cells transfection and injection,Method No.1),and fragments(tissues transfection and injection,Method No.2).Transfection efficiencies were compared between the two methods in vitro.Then GFP transfected glandular cells and stromal cells suspension were injected into nude mice subcutaneously(Method No.1),taking Method No.2 as a comparison.In vivo observation last for 25 days,and positive rates and duration times of fluorescent lesions were calculated.Histological examination was used to confirmed lesion formation.[Results]On the fifth day after injection,lesion positive rate of Method No.1 was 88.9%,which was statistically significantly higher than that of Method No.2(22.2%),P=0.015＜0.05.The fluorescent positive duration of Method No.1 and No.2 were 12 ± 8 days and 7±4 days.The structures of lesions were all identified as human original endometrium by histological examination,including HE staining and immunofluoresceney.[Conclusion]Noninvasive animal model of endometriosis can be built up by subcutaneously injection of Ad-EGFP transfected endometrial glandular cells and stromal cells suspension with higher positive rate and longer observation time