简介：AbstractBackground:According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.Methods:We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.Results:pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient’s study partner language domain could predict progression to dementia in A+T+MCI within 2 years.Conclusions:In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.

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简介：很多研究调查了外部煽动性的索引，包括根据痴呆的子类型的血浆cytokines和相关分子，然而并非在温和认知缺陷(媒体控制接口)。在这研究，我们使用了复合cytokine试金作为amnestic和non-amnestic与媒体控制接口subtyped在病人估计22cytokines的血浆层次，根据认知特征。当比较血浆生长因素，chemokines和cytokines的层次时，血浆单核白血球铺平趋化性的蛋白质3(MCP-3)，并且贝它神经生长因素(在这二的-NGF)组织，他们被发现比在non-amnestic媒体控制接口病人在amnestic媒体控制接口病人显著地更高级，在好久调整和性以后。这建议血浆MCP-3和-NGF可能在区分媒体控制接口的子类型是有用的。

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简介：摘要ObjectiveBecause the reliability of repetitive transcranial magnetic stimulation (rTMS) in treating poststroke cognitive impairment has not been convincingly demonstrated, we systematically examined the effectiveness of this regimen with 2 protocols.MethodsWe randomly allocated 41 patients with poststroke cognitive impairment to receive 5 Hz rTMS (n＝11), intermittent theta burst stimulation (iTBS; n＝15) or sham stimulation (n＝15). Each group received 10 stimulation sessions over the left dorsolateral prefrontal cortex. We performed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Beck Depression Inventory at baseline and after the intervention.ResultsThe 5 Hz rTMS group showed significantly greater improvement than the sham group in RBANS total score (P＝0.006), attention (P＝0.001) and delayed memory (P<0.001). The iTBS group showed significantly greater improvement than the sham group in RBANS total score (P＝0.005) and delayed memory (P＝0.007). The 5 Hz rTMS group exhibited a superior modulating effect in attention compared to the iTBS group (P＝0.016). Patients without comorbid hypertension (P＝0.008) were predisposed to favourable therapeutic outcomes.ConclusionsOur results demonstrated that both 5 Hz rTMS and iTBS were effective for poststroke cognitive impairment in terms of global cognition, attention and memory function; the domain of attention was susceptible to 5 Hz modulation. Treatment with 5 Hz rTMS may slow cognitive decline, representing both a pivotal process in poststroke cognitive impairment and an aspect of neuroplasticity that contributes to disease-modifying strategies.

简介：摘要ObjectiveThis study aims to figure out cerebral functional manipulation of rTMS in patients with PSCI through using the resting-state functional magnetic resonance imaging (rs-fMRI)．MethodsThirty patients with PSCI were recruited and randomly allocated into two groups: the rTMS intervention group and control group. The rTMS intervention group was given 20 min of 5 Hz rTMS (or control) over left dorsolateral prefrontal cortex (DLPFC) besides routine cognitive intervention training for 3 consecutive weeks, five times per week, on weekdays. Cognition performance was assessed by the Minimum Mental State Examination (MMSE) and Montreal cognitive assessment (MoCA). Neural activity and functional connectivity (FC) changes were acquired by rs-fMRI with fractional amplitude of low-frequency fluctuation (fALFF) and seed-based correlation analysis.ResultsCognition improvements were observed both in rTMS intervention group and control group (P<0.01), while the rTMS group got more significant improvent than control group (P<0.05). To be specified, compared with the control group, the rTMS group got higher fALFF values in these brain regions including superior temporal gyrus, inferior frontal gyrus and parahippocampal gyrus, while lower fALFF values in middle temporal gyrus, middle frontal gyrus and fusiform gyrus. In addition, the rTMS group showed increased FC between LDPFC and toprecuneus, inferior temporal gyrus, middle and inferior frontal gyrus and marginal gyrus, while decreased FC between LDPFC and middle temporal gyrus and thalamus.ConclusionsThe increase and decrease of neural activity and FC in cognition-related regions detected by rs-fMRI are good indicators to clarify the underlining mechanisms of rTMS on PSCI.

简介：摘要ObjectivePost-stroke cognitive impairment (PSCI) is resistant to treatment. Recent studies have widely applied repetitive transcranial magnetic stimulation (rTMS) to treat various brain dysfunctions, such as post-stroke syndromes. Nonetheless, a protocol for PSCI has not been established. Therefore, this study is aimed to evaluate the therapeutic effect of our high-frequency rTMS protocol for PSCI during the chronic phase of stroke.MethodsIn this prospective study, ten patients with PSCI were enrolled and received high-frequency rTMS on the ipsilesional dorsola-teral prefrontal cortex (DLPFC) for 10 sessions (5 days per week for 2 weeks). Cognitive and affective abilities were assessed at baseline and 2 and 14 weeks after rTMS initiation. To investigate the therapeutic mechanism of rTMS, the mRNA levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β，transforming growth factor beta [TGF-β], and tumor necrosis factor alpha [TNF-α]) in peripheral blood samples were quantified using reverse transcription polymerase chain reaction, and cognitive functional magnetic resonance imaging (fMRI) was conducted at baseline and 14 weeks in two randomly selected patients after rTMS treatment.ResultsThe scores of several cognitive evaluations, i．e., the Intelligence Quotient (IQ) of Wechsler Adult Intelligence Scale, auditory verbal learning test (AVLT), and complex figure copy test (CFT), were increased after completion of the rTMS session. After 3 months, these improvements were sustained, and scores on the Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) were also increased (P<0.05). While the Geriatric Depression Scale (GeDS) did not show change among all patients, those with moderate-to-severe depression showed amelioration of the score, with marginal significance. Expression of pro-inflammatory cytokines was decreased immediately after the ten treatment sessions, among which, IL-1β remained at a lower level after 3 months. Furthermore, strong correlations between the decrease in IL-6 and increments in AVLT (r＝0.928) and CFT (r＝0.886) were found immediately after the rTMS treatment (P<0.05). Follow-up fMRI revealed significant activation in several brain regions, such as the medial frontal lobe, hippocampus, and angular area.ConclusionsHigh-frequency rTMS on the ipsilesional DLPFC may exert immediate efficacy on cognition with the anti-inflammatory response and changes in brain network in PSCI, lasting at least 3 months.

简介：摘要ObjectiveTo identify the effects of rTMS intervention on PSCI patients and its potential neural correlates to behavioral improvements.MethodsWe recruited 34 PSCI patients for 20 sessions of 10 Hz rTMS or no-stim control treatments over the left dorsal lateral prefrontal cortex (DLPFC). Cognitive function was evaluated with the Montreal Cognitive Assessment Scale, Victoria Stroop Test, Rivermead Behavior Memory Test, and Activities of Daily Living (ADL) assessed with the Modified Barthel Index. 14 patients received functional MRI scan, a useful non-invasive technique of determining how structurally segregated and functionally specialized brain areas were interconnected, which was reflected by blood oxygenation level-dependent signals. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were applied as the analytical approaches, which were used to measure the resting-state brain activity and functional connection.ResultsrTMS improved cognitive functions and ADLs for PSCI patients relative to patients who received no-stim control treatment. The cognitive improvements correlated to increased ALFF of the left medial prefrontal cortex, and increased FC of right medial prefrontal cortex and right ventral anterior cingulate cortex.Conclusions10 Hz rTMS at DLPFC could improve cognitive function and quality of life for PSCI patients, which is associated with an altered frontal cortical activity.

简介：摘要IntroductionDelayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective.Patient concerns and diagnosesWe report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission.Interventions and outcomesAlthough hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score from 9 to 28 points in Case 1 and an improved Hasegawa′s dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning.ConclusionPhysicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

简介：CurrentevidenceshowsthatapolipoproteinE(APOE),apolipoproteinCI(APOC1)andlowdensitylipoproteinreceptor-relatedprotein(LRP)variationsarerelatedtolate-onsetAlzheimer’sdisease.However,itremainsunclearifgeneticpolymorphismsinthesegenesareassociatedwithcognitivedeclineinlate-onsetAlzheimer’sdiseasepatients.Weperformeda30-monthlongitudinalcohortstudytoinvestigatetherelationshipbetweenAlzheimer’sdiseaseandAPOE,APOC1,andLRP.Inthisstudy,78ChineseHanpatientswithlate-onsetAlzheimer’sdiseasewererecruitedformGuangxiZhuangAutonomousRegioninChina.APOE,APOC1,andLRPgenotypingwasperformedusingpolymerasechainreaction-restrictionfragmentlengthpolymorphisms.TheMini-MentalStateExaminationandClinicalDementiaRatingScalewereusedtoassesspatients’cognitivefunction.Aftera30-monthfollow-upperiod,wefoundasignificantreductioninMini-MentalStateExaminationtotalscore,ahigherproportionofpatientsfulfillingcognitiveimpairmentprogressioncriteria,andahigherproportionofAPOC1H2carriersinAPOEε4carrierscomparedwithnon-carriers.Inaddition,theAPOEε4allelefrequencywassignificantlyhigherinthecognitiveimpairmentprogressiongroupcomparedwiththenon-cognitiveimpairmentprogressiongroup.Inconclusion,APOEε4playsanimportantroleinaugmentingcognitivedecline,andAPOC1H2mayactsynergisticallywithAPOEε4inincreasingtheriskofcognitivedeclineinChinesepatientswithlate-onsetAlzheimer’sdisease.

简介：AbstractBackground:Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.Methods:We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician’s global assessment (sPGA) at week 12.Results:The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.Conclusion:During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.Trial Registration:Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen. aspx?proj=6300.

简介：正面思考是什么呢?正面思考意味着只去想好的事情、对事情成功有益的因素，而不考虑任何会引起事情没有价值、无法实施、导致失败的因素。

简介：Thecompletelypositivematricesareimportantinthestudyofblockdesignsarizingincombinatorialanalysis(see[11])andarerelatedtocopositivematrices,whichhaveappli-cationsincontroltheoryandinmultimobicalprogramming(see[12]).Ann×nmatrixAissaidtobecompletelypositiveifAcanbefactoredasA=BB~Tforsomen×mrealmatrixBwithnonnegativeentriesforsomem<∞.IfAisacompletelypositivematrix,thenthesmallestnumberofcolumnsinanonnegativematrixBsuchthat

简介：Rheumatoidarthritis(RA)isasystemic,autoimmunediseasethatpresentwithintra-articularandextra-articularmanifestations.AuditorysystemmaybeinvolvedduringthecourseofRAdiseaseduetonumbersofpathologies.ThelinkbetweenhearingimpairmentandRAhasbeendiscussedinthepreviousliterature.InthisstudyweprovideanupdateontheclinicalaspectofhearingimpairmentinRA.WesuggesttotesthearinginallnewlydiagnosedRApatientsatdiagnosisaswellasregularlyduringthecourseofdisease.

简介：AbstractPrecision medicine requires coordinated and integrated evidence-based combinatorial approaches so that diagnosis and treatment can be tailored to the individual patient. In this context, the treatment approach to mild obstructive sleep apnea (OSA) is fraught with substantial debate as to what is mild OSA, and as to what constitutes appropriate treatment. As such, it is necessary to first establish a proposed consensus of what criteria need to be employed to reach the diagnosis of mild OSA, and then examine the circumstances under which treatment is indicated, and if so, whether and when anti-inflammatory therapy (AIT), rapid maxillary expansion (RME), and/or myofunctional therapy (MFT) may be indicated.

简介：Theadenomatoidodontogenictumorischaracterizedbytheformationofduct-likestructuresandappearanceofeosinophilicmaterials.Eosinophilicmaterialsshowamorphousmassordropletsamongtheepithelialcells.Intheduct-likestructures,itshowsathinlayerofbasementmembranel...

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简介：ObjectivesToevaluateperipheralauditorydysfunctioninseniledementiaofAlzheimer'sdisease(AD)anditsrelationshipwithcognitivedysfunction.MethodsPuretonethresholds,wordrecognitionscores(WRS),acousticimmittanceandauditorybrain-stemresponses(ABR)weretestedtoevaluatetheauditoryfunctionin43ADpatientsand50normalsubjects.ThetestreliabilityinthesesubjectswasexaminedbeforethetestresultswereevaluatedfortheircorrelationwiththeMiniMentalStateExamination(MMSE)score.ResultsTherewerenostatisticallysignificantdifferencesinperipheralauditoryfunctionsbetweenthetwoearsinthetestedsubjectsorbetweenthetwogroupswhentheauditometricresultsoftherightearwerecompared(P>0.05).Also,therewerenostatisticallysignificantdifferencesbetweenthetwogroupswhenaudiometrictestreliability,acousticimpedanceandABRresultswerecompared(P>0.05).ConclutionsThepuretoneaudiometricthresholdandWRSinADpatientsaresimilartothoseincomparablenon-ADsenilesubjects.Peripheralauditorydysfunctionisnotrelatedtocognitivedysfunction.

简介：Thispaperinvestigatesthepositiverealcontrolproblemforuncertaindescriptorsystems.Theparametricuncertaintyisassumedtobenormbounded.Firstly,forthenominalsystem,anewpositiverealcharacterizationisgiven,whichisexpressedbyastrictlinearmatrixinequality(LMI)withoutequalityconstraints.Secondly,fortheuncertainsystem,necessaryandsufficientconditionsforthesolvabilityofthepositiverealcontrolproblemarederived.Basedontheseconditioosastatefeedbacklawisobtained,whichrenderstheresultantclosed-loopsystemrobustlypositivereal.