The Influence of Patent Foramen Ovale on the Clinical Features of Migraine without Aura: A Cross-Sectional Study.

Objective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA). Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann-Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test. Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores. Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.

α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson's Disease.

Circadian dysfunction is a common non-motor symptom in Parkinson's disease (PD). The potential influence of aggravated α-synuclein (SNCA) on circadian disruption remains unclear. SNCAA53T-overexpressing transgenic mice (SNCAA53T mice) and wild-type (WT) littermates were used in this study. The energy metabolism cage test showed differences in 24-h activity pattern between SNCAA53T and WT mice. When compared with the age-matched littermates, brain and muscle ARNT-like 1 (BMAL1) was downregulated in SNCAA53T mice. BMAL1 was downregulated in PC12 cells overexpressing SNCA. Degradation of BMAL1 protein remained unchanged after overexpression of SNCA, while its mRNA level decreased. miRNA (miR)-155 was upregulated by overexpression of SNCA, and downregulation of BMAL1 was partially reversed by transfection with miR-155 inhibitor. Our findings demonstrated that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155.

Association of concomitant headache with hypoperfusion in ischemic stroke: A multimodal CT-based study.

Previous investigations indicate that vessel wall elasticity may contribute to the occurrence of an ischemic stroke-associated headache. In this prospective study, the association between radiologic parameters of intracranial hemodynamic changes and concomitant headaches during the early phase of ischemic stroke was examined. Consecutive patients with acute ischemic stroke (AIS) from the First Affiliated Hospital of Soochow University were recruited and divided into two groups according to their questionnaire results and the International Classification of Headache Disorder 3 criteria. Baseline data, including stroke sub-types and neurological function, at admission and discharge were collected. Non-contrast computed tomography (CT), CT angiography, and CT perfusion were performed to assess intracranial hemodynamic changes. Multiple adjusted logistic models were used and possible confounding factors were included in sequential models. A total of 190 patients with AIS (93 headaches and 97 non-headache) were recruited. There were significant differences between the two groups in gender, hypertension, Alberta stroke program early CT score, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Furthermore, rCBV (adjusted odds ratio [OR] 0.160; 95% confidence interval [CI], 0.055-0.461; p < 0.001) and rCBF (adjusted OR, 0.309; 95% CI, 0.113-0.844; p < 0.05) were significantly associated with concomitant headache during the early phase of AIS in fully adjusted models. After adjusting for sociodemographic characteristics and other confounding factors, p values for the ORs were robust and intensified. Patients with lower rCBV and rCBF tended to experience the concomitant headache during the early phase of AIS. Regional hypoperfusion and microcirculation might play an important role in this separate clinical entity.

Depletion of B7-H4 from C3H10 T1/2 Mesenchymal Stem Cells Attenuates their Immunomodulatory Therapy in Experimental Autoimmune Encephalomyelitis Mice.

Considering the controversial issue of whether MSC therapy is effective in the treatment of multiple sclerosis, it is important to seek more powerful data to clarify the effect of MSCs. B7-H4 is a unique costimulatory molecule that belongs to the B7 ligand family and is broadly expressed in both lymphoid and non-lymphoid tissues. Previous studies have shown that B7-H4 is involved in regulating the progression of autoimmune diseases. However, its role in MSCs and stem cell transplantation remains unclear. In this study, we focus on C3H10 T1/2 cells, which are mouse-derived mesenchymal stem cells. And we investigated the role of B7-H4 in C3H10 T1/2 cells and explored its underlying mechanisms. As a result, downregulation of B7-H4 induced apoptosis and impaired the cell proliferation of C3H10 T1/2 cells. Further results showed that cells were arrested in the G0/G1 phase after knockdown of B7-H4. Furthermore, an EAE model was induced in female C57BL/6 mice by injecting MOG 35-55, and we investigated the effect of C3H10 T1/2 cell transplantation for the EAE model after downregulation of B7-H4 in vivo. We found that C3H10 cells can migrate to the area of spinal cord lesions, and depletion of B7-H4 attenuated the immunoregulatory effect of C3H10 T1/2 cells in vivo. Together, our findings suggest that B7-H4 is important for C3H10 cells to exert neurorestoration and therefore may be a potential molecular target for stem cell transplant strategies.

Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials.

BACKGROUND: To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of Parkinson's disease (PD). METHODS: The databases of Medline, EMBASE, and the Cochrane Library were searched for eligible randomized controlled trials comparing focused ultrasound surgery (FUS) group vs. sham procedure group in PD. Weighted mean differences and standardized mean differences with corresponding 95% confidence intervals were used to summarize the primary outcome, namely, the effect of MRgFUS to improve limb tremor in PD patients and adverse events, and the secondary outcome, which is the effect of MRgFUS in improving the quality of life, activities of daily living, and non-motor symptoms. RESULTS: The pooled analysis comprised 2 studies. The blinded phase lasted for 4 months in one experiment and up to 3 months in the other. The FUS group showed significant improvement in limb tremor on the treated side (SMD: - 1.20; 95% CI: - 2.06, - 0.34) and the ability to perform daily activities (SMD: - 0.86; 95% CI: - 1.41, - 0.32) compared to the sham group, but there were no significant group differences in other indicators. Of the process-related adverse events, dizziness (OR: 4.68; 95% CI: 1.20, 18.23) was more common in the treatment group, with no group differences in the remaining adverse events. CONCLUSIONS: These findings suggest beneficial effects of MRgFUS in PD patients with no serious side effects. Larger multicenter studies are needed in the future to select the most appropriate target and surgical device setup parameters.

Long non-coding RNA THRIL inhibits miRNA-24-3p to upregulate neuropilin-1 to aggravate cerebral ischemia-reperfusion injury through regulating the nuclear factor κB p65 signaling.

PURPOSE: The aim of this study was to investigate the role of the tumor necrosis factor and HNRNPL related immunoregulatory long non-coding RNA (THRIL) in cerebral ischemia-reperfusion injury. METHODS: A rat middle cerebral artery occlusion/ischemia-reperfusion (MCAO/IR) model and an oxygen glucose deprivation/reoxygenation (OGD/R) cell model were constructed. THRIL was knocked down using siTHRIL. Neurological deficit score was detected based on the criteria of Zea-Longa. Brain region 2,3,5-Triphenyltetrazolium (TTC) staining and quantitative analysis of cerebral infarction volume, RT-qPCR, and fluorescence immunostaining were performed for assessing THRIL expression. MTT assay was used to detect the cell proliferation ability after transfection, TUNEL assay was applied to detect apoptosis, and western blot and ELISA detected related protein expression. A dual luciferase reporter system and RIP assay were used to confirm the target relationship. RESULTS: THRIL was upregulated in both in vitro and in vivo models of brain ischemia-reperfusion injury. Knockdown of THRIL attenuated OGD/R neuronal apoptosis and OGD/R-induced inflammation. THRIL targeted and regulated the expression of miR-24-3p/neuropilin-1 (NRP1) axis. THRIL silencing significantly improved the neurological functioning of rats in the MCAO/R model by miR-24-3p/NRP1/NF-κB p65 signaling pathway. CONCLUSION: THRIL could aggravate cerebral ischemia-reperfusion injury by competitively binding to miR-24-3p to promote the upregulation of NRP1 and further promoted the activation of the NF-κB p65 signaling pathway.

LMTK2 regulates inflammation in lipopolysaccharide-stimulated BV2 cells.

Microglia activation plays vital roles in neuroinflammatory pathologys. Lemurs tyrosine kinase 2 (LMTK2) was reported to regulate NF-κB signals. In the present study, the roles of LMTK2 were investigated in lipopolysaccharide (LPS)-treated BV-2 cells. Reverse transcription-quantitative (RT-q)PCR and western blotting (WB) were utilized to analyze LMTK2 levels in LPS-treated BV2 cells. MTT assay determined cell viabilities. Nitric oxide (NO) and prostaglandin E2 (PGE2) levels were assessed through Griess and enzyme-linked immunosorbent assay (ELISA), respectively. The expression level of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected through RT-qPCR and WB. The release of inflammatory mediators under LPS stimulation, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-10, were analyzed through ELISA. WB was used to analyze the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/NAD(P)H dehydrogenase quinone 1 (NQO1) signal pathway. The results showed that the levels of the inflammatory mediators, iNOS, NO, COX-2 and PGE2, along with pro-inflammatory factors, TNF-α, IL-1ß and IL-6, were significantly decreased following the induction of exogenous LMTK2 expression by LMTK2 overexpression plasmids in LPS-induced BV2 microglia. In contrast, anti-inflammatory factor IL-10 showed obvious decrease. Additionally, LMTK2 overexpression induced the elevation of Nrf2 in the cytoplasm and nucleus, along with the upregulation of HO-1 and NQO1 expression. In conclusion, LMTK2 is postulated to regulate neuroinflammation possibly through Nrf2 pathway. The present study is essential to reveal the underlying function of LMTK2 and to identify novel therapeutic targets for drug development in treating neuroinflammation.

Diagnostic performances of neutrophil to lymphocyte ratio and lymphocyte to monocyte ratio in acute ischemic stroke caused by cervicocranial arterial dissection.

BACKGROUND: Inflammation plays an important role in the initiation and progression of cervicocranial arterial dissection (CCAD). New inflammatory indices derived from full cell blood count may be associated with increased risk of acute ischemic stroke (AIS) caused by CCAD. The goal of this study is to evaluate the diagnostic performances of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) in CCAD. METHOD: We retrospectively analyzed 52 patients with AIS caused by CCAD from emergency room (group I), 51 patients with CCAD from emergency room or clinic(group II) and 52 controls (group III), age and sex matched. Data were collected on the admission including NLR and LMR. RESULTS: Neutrophil to lymphocyte ratio and LMR have significant differences among three groups, especially in group I vs both groups II and III (P < .001). There was a negative correlation between admission NLR and LMR. Low LMR level and high NLR level may be associated with severity of AIS caused by CCAD and significantly predict AIS in CCAD. The area under the curve of NLR and LMR were 0.77 and 0.71, respectively, on receiver operating characteristic curve analysis. The optimal cutoff values of NLR and LMR that best discriminated AIS were 2.35 (81% sensitivity and 63% specificity) and 3.67 (64% sensitivity and 77% specificity). CONCLUSIONS: Neutrophil to lymphocyte ratio neutrophil to lymphocyte ratio and LMR may contribute to the diagnostic evaluation and prompt immediate therapy in patients with CCAD.

Mitochondrial Uncouplers Confer Protection by Activating AMP-Activated Protein Kinase to Inhibit Neuroinflammation Following Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a disease with high disability and mortality rates. Currently, the efficacy of therapies available for ICH is limited. Microglia-mediated neuroinflammation substantially exacerbates brain damage following ICH. Here, we investigated whether mitochondrial uncouplers conferred protection by suppressing neuroinflammation following ICH. To mimic ICH-induced neuroinflammation in vitro, we treated microglia with red blood cell (RBC) lysate. RBC lysate enhanced the expression of pro-inflammatory cytokines in microglia. A clinically used uncoupler, niclosamide (Nic), reduced the RBC lysate-induced expression of pro-inflammatory cytokines in microglia. Moreover, Nic ameliorated brain edema, decreased neuroinflammation, and improved neurological deficits in a well-established mouse model of ICH. Like niclosamide, the structurally unrelated uncoupler carbonyl cyanide p-triflouromethoxyphenylhydrazone (FCCP) reduced brain edema, decreased neuroinflammation, and improved neurological deficits following ICH. It has been reported that mitochondrial uncouplers activate AMP-activated protein kinase (AMPK). Mechanistically, Nic enhanced AMPK activation following ICH, and AMPK knockdown abolished the beneficial effects of Nic following ICH. In conclusion, mitochondrial uncouplers conferred protection by activating AMPK to inhibit microglial neuroinflammation following ICH.

Down-regulation of UBA6 exacerbates brain injury by inhibiting the activation of Notch signaling pathway to promote cerebral cell apoptosis in rat acute cerebral infarction model.

This study aimed to examine the UBA6 role in brain injury mediated by acute cerebral infarction (ACI). In order to screen potential therapeutic targets for ACI, two expression profiles, including GSE97537 and GSE97533 datasets, were downloaded from the GEO database. The Venn method to identify the common DEGs. 68 up-regulated overlapping DEGs and 51 down-regulated overlapping DEGs were used to construct the PPI network by STRING online database. UBA6 was identified as a hub gene by the CytoHubba plugin from Cytoscape. GO and KEGG pathway enrichment analyses were conducted using DAVID online website. UBA6 knockout exacerbated MCAO-mediated brain injury and cell apoptosis in rat brain tissues by H&E and TTC staining and TUNEL assay. The results of flow cytometry and western blot assays further demonstrated that UBA6 inhibition induced the apoptosis of hippocampal neurons and increased cleaved-caspase-3/9 protein levels. Notch1, NICD and Hes1 protein levels were suppressed by down-regulated UBA6. UBA6 was lowly expression in poor prognosis group of 100 patients with ACI. Logistic regression analysis indicated that hypertension, blood glucose, urokinase dose, UBA6 expression and AF were the main risk factors of poor prognosis after thrombolytic therapy for patients with ACI. The ROC curve analysis showed that the sensitivity and specificity of UBA6 was good (sensitivity 100%, specificity 89%, and AUC = 0.772) to be used to evaluate the poor prognosis of ACI. In conclusion, down-regulated UBA6 intensified MCAO-induced brain injury by inhibiting the activation of Notch signaling pathway to promote the apoptosis of hippocampal neurons and was used to predict the poor prognosis of ACI.

Publisher Correction: Unbalanced Expression of ICOS and PD-1 in Patients with Neuromyelitis Optica Spectrum Disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

miR-22 and cerebral microbleeds in brainstem and deep area are associated with depression one month after ischemic stroke.

In this study, we aimed to explore the relationship among miR-22, deep cerebral microbleeds (CMBs), and post-stroke depression (PSD) 1 month after ischemic stroke. We consecutively recruited 257 patients with first-ever and recurrent acute cerebral infarction and performed PSD diagnosis in accordance with the Diagnostic and Statistical Manual IV criteria for depression. Clinical information, assessments of stroke severity, and imaging data were recorded on admission. We further detected plasma miR-22 using quantitative PCR and analyzed the relationship among miR-22, clinical data, and PSD using SPSS 23.0 software. Logistic regression showed that deep (OR=1.845, 95%CI: 1.006-3.386, P=0.047) and brain stem CMBs (OR=2.652, 95%CI: 1.110-6.921, P=0.040), as well as plasma miR-22 levels (OR=2.094, 95%CI: 1.066-4.115, P=0.032) were independent risk factors for PSD. In addition, there were significant differences in baseline National Institutes of Health Stroke Scale scores (OR=1.881, 95%CI: 1.180-3.011, P=0.007) and Widowhood scores (OR=1.903, 95%CI: 1.182-3.063, P=0.012). Analysis of the receiver operating curve (AUC=0.723, 95%CI: 0.562-0.883, P=0.016) revealed that miR-22 could predict PSD one month after ischemic stroke. Furthermore, plasma miR-22 levels in brainstem and deep CMBs patients showed an upward trend (P=0.028) relative to the others. Patients with acute ischemic stroke, having brainstem and deep cerebral microbleeds, or a higher plasma miR-22 were more likely to develop PSD. These findings indicate that miR-22 might be involved in cerebral microvascular impairment and post-stroke depression.

Elevated neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict post-stroke depression with acute ischemic stroke.

Post-stroke depression (PSD) is the most prevalent psychiatric complication of acute ischemic stroke. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are indicators of inflammation and are associated with stroke and depression. Therefore, the purpose of the present study was to examine the relationship between NLR/PLR and PSD. Retrospective analysis was carried out in 376 patients with first-ever acute ischemic stroke in the First Affiliated Yijishan Hospital of Wannan Medical College between March 2015 and September 2017. Patients were divided into PSD (n=104; 27.7%) and non-PSD (n=272; 72.3%) groups according to the Diagnostic and Statistical Manual of Mental Disorders-IV criteria at 6 months after stroke. Clinical data were collected retrospectively. NLR and PLR were acquired retrospectively from the routine blood tests performed at admission. A total of 120 healthy volunteers from the physical examination center in the First Affiliated Yijishan Hospital of Wannan Medical College were recruited as controls. Using logistic regression analysis, NLR (≥4.02) and PLR (≥203.74) were independently associated with PSD. NLR, odds ratio (OR) 3.926, 95% confidence intervals (CI, 2.365-7.947), P<0.001; PLR, OR 3.853, 95% CI (2.214-6.632), P=0.002. The ability of the combined index [area under the receiver operating characteristic curve, 0.701; 95% CI (0.622-0.780); P<0.001] to diagnose PSD was greater than that of either ratio alone. Higher NLRs and PLRs (≥4th quartile) were associated with PSD with a 5.79-fold (P<0.001) increase compared with lower levels of both. Higher NLRs and PLRs were found to be associated with depression 6 months after stroke, and the combined index was more meaningful than either alone in the early clinical detection of PSD.

Luteolin alleviates neuroinflammation via downregulating the TLR4/TRAF6/NF-κB pathway after intracerebral hemorrhage.

The activation of microglia and inflammatory responses is essential for the process of intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we investigated the effects of luteolin on ICH-induced SBI and the potential mechanisms. Autologous blood was injected to establish the ICH model in vivo, and oxyhemoglobin (OxyHb) was used to mimic the ICH model in vitro. We found that the administration of luteolin significantly improved motor and sensory impairments and inhibited neuronal cell degeneration in vivo. In the in vitro study, the decrease of the neuronal cell viability induced by activated microglia was alleviated by luteolin treatment. Furthermore, by antagonizing the activation of the Toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-κB (NF-κB) signaling pathway, the ICH-induced elevation of cytokine release was decreased after treatment with luteolin, which was confirmed both in vivo and in vitro. Additionally, we found that luteolin engaged with TRAF6 and inhibited the ubiquitination of TRAF6. Taken together, our findings demonstrate the neuroprotective effects of luteolin after ICH and the potential mechanisms, which suggest that luteolin is a potential therapeutic candidate for ICH treatment.

Severity and Its Contributing Factors in Patients With Vestibular Migraine: A Cohort Study.

Objective: As a recently defined disease entity, vestibular migraine (VM) is a variant of migraine with broad spectrum of manifestations. We evaluated a prospective cohort of patients with VM in two centers to assess severity of VM attacks and investigate its contributing factors in patients with VM. Methods: Adult participants with the diagnosis of VM or probable VM were enrolled according to the 2012 International Headache Society-Bárány Society Criteria. Every outpatient was followed up for 6 months to record the occurrence of VM attacks. Clinical data such as age, sex, number of VM attacks, severity on the visual analog scale, and lipid intake were collected and analyzed. Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Horne and Ostberg Morningness-Eveningness Questionnaires, and Pittsburgh Sleep Quality Index were also administered to find contributing factors. Results: During a 6-month clinical follow-up, 313 VM attack were reported. According to the Visual Analog Scale, the patients were divided into two groups. Then univariate and multivariable analyses were conducted. Among the risk factors, duration of illness (adjusted OR, 1.041; 95% CI, 1.010-1.073; P = 0.009), time of onset: 00:00:00-12:00:00 (adjusted OR, 3.961; 95% CI, 1.966-7.979; P < 0.001) and PSQI scores (adjusted OR, 1.086; 95% CI, 1.002-1.178; P = 0.046) were significantly associated with the severity of VM attack assessed by VAS. Conclusion: The data suggest that patients tended to experienced more severe VM attacks in early hours of a day, especially for those sufferers with longer duration of illness or poor sleep quality. Targeted management of such factors is required to reduce the severity of attacks.

MicroRNA-6862 inhibition elevates sphingosine kinase 1 and protects neuronal cells from MPP+-induced apoptosis.

MPP+ (1-methyl-4-phenylpyridinium)-induced dopaminergic neuronal cell apoptosis is associated with sphingosine kinase 1 (SphK1) inhibition. We here tested the potential effect of microRNA-6862 (miR-6862), a novel SphK1-targeting miRNA, on MPP+-induced cytotoxicity in neuronal cells. MiR-6862 locates in the cytoplasm of SH-SY5Y neuronal cells. It directly binds to SphK1 mRNA. In SH-SY5Y cells and HCN-2 cells, ectopic overexpression of miR-6862 decreased SphK13'-untranslated region luciferase reporter activity and downregulated its expression. miR-6862 inhibition exerted opposite activity and elevated SphK1 expression. In neuronal cells, MPP+-induced cell death was significantly inhibited through miR-6862 inhibition. Conversely, ectopic overexpression of miR-6862 or CRISPR/Cas9-induced SphK1 knockout augmented MPP+-induced apoptosis in the neuronal cells. Importantly, antagomiR-6862 failed to inhibit MPP+-induced apoptosis in SphK1-knockout SH-SY5Y cells. These results suggest that inhibition of miR-6862 induces SphK1 elevation and protects neuronal cells from MPP+-induced cell death.

Applying minimal RNA-seq of peripheral blood platelet mRNA to reveal novel biomarkers in male patients with cerebral stroke.

Cerebral stroke is caused by the reduction or disruption of the blood supply to the brain, which results in cell death. Currently, the diagnosis of stroke is troublesome and expensive. In this study, samples of peripheral blood from eight male stroke patients and four male healthy controls were collected. RNA-seq of platelets was performed to detect the differential expression of mRNA in platelets isolated from the samples. Totally, 1091 (429 up-regulated and 662 down-regulated) differentially expressed genes were identified in patients with stroke compared with healthy controls. Analyses based on Gene Ontology and the KEGG pathway revealed that most annotated genes were involved in graft-versus-host disease, cell adhesion molecules signaling pathways, inflammation-related pathways, and so on. RNA expression levels of 15 inflammation-related genes were analyzed using qRT-PCR, especially egr2, which acts as a protector against stroke. In brief, RNA-seq analysis of platelets from all the samples indicated novel candidate genes and pathways that had the potential to be applied to clinical molecular diagnosis of stroke. Besides, this study provided insights into the function and underlying mechanism of stroke.

miR-22 and cerebral microbleeds in brainstem and deep area are associated with depression one month after ischemic stroke

In this study, we aimed to explore the relationship among miR-22, deep cerebral microbleeds (CMBs), and post-stroke depression (PSD) 1 month after ischemic stroke. We consecutively recruited 257 patients with first-ever and recurrent acute cerebral infarction and performed PSD diagnosis in accordance with the Diagnostic and Statistical Manual IV criteria for depression. Clinical information, assessments of stroke severity, and imaging data were recorded on admission. We further detected plasma miR-22 using quantitative PCR and analyzed the relationship among miR-22, clinical data, and PSD using SPSS 23.0 software. Logistic regression showed that deep (OR=1.845, 95%CI: 1.006-3.386, P=0.047) and brain stem CMBs (OR=2.652, 95%CI: 1.110-6.921, P=0.040), as well as plasma miR-22 levels (OR=2.094, 95%CI: 1.066-4.115, P=0.032) were independent risk factors for PSD. In addition, there were significant differences in baseline National Institutes of Health Stroke Scale scores (OR=1.881, 95%CI: 1.180-3.011, P=0.007) and Widowhood scores (OR=1.903, 95%CI: 1.182-3.063, P=0.012). Analysis of the receiver operating curve (AUC=0.723, 95%CI: 0.562-0.883, P=0.016) revealed that miR-22 could predict PSD one month after ischemic stroke. Furthermore, plasma miR-22 levels in brainstem and deep CMBs patients showed an upward trend (P=0.028) relative to the others. Patients with acute ischemic stroke, having brainstem and deep cerebral microbleeds, or a higher plasma miR-22 were more likely to develop PSD. These findings indicate that miR-22 might be involved in cerebral microvascular impairment and post-stroke depression.

The items in the Chinese version of the Montreal cognitive assessment basic discriminate among different severities of Alzheimer's disease.

BACKGROUND: To determine whether items of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) could discriminate among cognitively normal controls (NC), and those with mild cognitive impairment (MCI), mild Alzheimer's disease (AD), and moderate-severe (AD), as well as their sensitivity and specificity. METHODS: MCI (n = 456), mild AD (n = 502) and moderate-severe AD (n = 102) patients were recruited from the memory clinic, Huashan Hospital, Shanghai, China. NC (n = 329) were recruited from health checkup outpatients. Five MoCA-BC item scores were collected in interviews. RESULTS: The MoCA-BC orientation test had high sensitivity and specificity for discrimination among MCI, mild AD and moderate-severe AD. The delayed recall memory test had high sensitivity and specificity for MCI screening. The verbal fluency test was efficient for detecting MCI and differentiating AD severity. CONCLUSIONS: Various items of the MoCA-BC can identify MCI patients early and identify the severity of dementia.