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Xuan-qiang Tu,1,* Ze-hua Lai,1,* Yu Zhang,2 Kai-qi Ding,1 Fei-yue Ma,3 Guo-Yuan Yang,1 Ji-rong He,3 Li-li Zeng1 1Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology and Institute of Neurology, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Neurology and Institute of Neurology, Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-li Zeng No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, People’s Republic of ChinaTel +86-13816290607Email llzeng@126.comJi-rong He No. 149 Chongqing South Road, Huangpu District, Shanghai, People’s Republic of ChinaTel +86-13162762045Email kyo3shao@aliyun.comObjective: This study aimed to explore the correlation between white matter hyperintensity (WMH) and post-stroke depression (PSD) at 3 months, and to further investigate sex differences in the pathogenesis of PSD.Methods: A total of 238 consecutive patients with acute cerebral infarction were recruited. PSD was assessed at 2 weeks and at 3 months after stroke onset. All stroke cases were divided into four subgroups according to the diagnosis of depression at two time nodes: continuous depression; depression remission; late-onset PSD; and continuous non-depression. The Fazekas and Scheltens visual rating scales were adopted to assess WMH.Results: Logistic regression revealed that the presence of periventricular white matter hyperintensity (PVWMH) at baseline in male patients was an independent risk factor for PSD at 3 months. Further subgroup analysis revealed that PVWMH was associated with late-onset PSD in males, but not with continuous depression 3 months after stroke. Male acute stroke patients with PVWMH at baseline were more likely to develop PSD at 3 months, especially late-onset PSD.Conclusion: Our data suggest that sex differences may influence the pathogenesis of PSD.Keywords: sex difference, acute cerebral infarction, leukoencephalopathy, affective disorder, post-stroke depression

Vascular cognitive impairment (VCI) is the most common type of dementia after Alzheimer's disease (AD). Effective treatments for VCI are currently lacking. MicroRNA (miR)- 140-5p is associated with cerebral ischemia and poststroke depression, but its relationship with VCI remains unknown. A VCI model was established by bilateral common carotid artery occlusion (BCCAO) for 17 min in mice. Neurogenesis was evaluated by immunostaining for Nestin/bromodeoxyuridine (BrdU), NeuN/BrdU, and doublecortin (DCX)/BrdU. Neuroplasticity was assessed by quantifying synapsin-I and postsynaptic density protein 95 (PSD-95) protein levels. Predicted target genes were screened and verified using the dual luciferase reporter gene system. MiR-140-5p was upregulated in the hippocampus of the BCCAO mice 2 weeks following ischemia. Compared with control groups, the AAV-miR-140-5p group exhibited poorer cognitive performance alongside lower numbers of DCX/BrdU and NeuN/BrdU and less synapsin-I and PSD-95 in the dentate gyrus (P 0.05). MiR-140-5p overexpression decreased the predicted target gene Prox1. Dual luciferase reporter system confirmed that Prox1 was a direct target site for miR-140-5p. In conclusion, our results suggest that miR-140-5p inhibits neurogenesis and neuroplasticity via downregulation of Prox1 and aggravates VCI. Our findings highlight that miR-140-5p is involved in the pathological process of VCI and provides information for the development of new treatments, which may need further inhibition tests to verify.

Kai-qi Ding,* Ze-hua Lai,* Yu Zhang, Guo-yuan Yang, Ji-rong He, Li-li Zeng Department of Neurology and Institute of Neurology, Ruijin Hospital/Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-li Zeng No. 197 Ruijin Second Road, Huangpu District, Shanghai, 200025, People’s Republic of ChinaTel +86-13816290607Email llzeng@126.comJi-rong He No. 149 Chongqing South Road, Huangpu District, Shanghai, People’s Republic of ChinaTel +86-13162762045Email kyo3shao@aliyun.comPurpose: To explore the relationship between the monocyte-to-lymphocyte ratio (MLR) and depression three months after acute ischemic stroke.Patients and Methods: From May 2013 to September 2014, 203 patients with acute ischemic stroke were recruited within 7 days post-stroke from Shanghai Ruijin Hospital and blood samples were collected after admission. The Hamilton Depression Scale and Clinical Review were evaluated at 3 months after stroke. Based on the Diagnostic and Statistical Manual of Mental Disorders-IV diagnostic criteria, we divided patients into post-stroke depression (PSD) and non-PSD groups. We analyzed the intergroup difference in MLR and the contributing factors. Moreover, dynamic changes in monocytes, lymphocytes and MLR at four different time intervals for all the stroke patients and their relationship with PSD patients were also studied.Results: The NIHSS scores and MLR in the PSD group were significantly higher than in the non-PSD group (p< 0.05). Logistic regression analysis revealed MLR was an independent risk factor for PSD (odds ratio: 18.020, 95% confidence interval: 1.127‒288.195, p=0.041). MLR correlated negatively with cholesterol and low-density lipoprotein (r=− 0.160 and − 0.165, respectively, p< 0.05). Within 7 days post-acute ischemic stroke, monocytes gradually increased while lymphocytes remained unchanged for all the stroke patients. The MLR value was significantly higher in the PSD group than in the non-PSD group within 24 h post-stroke (p< 0.05), but there was no difference in the other three time-intervals between the two groups.Conclusion: The admission MLR, particularly within 24 h post-stroke, was associated with PSD at 3 months, implying that the MLR might be involved in the PSD inflammatory mechanism.Keywords: MLR, depression, inflammation, acute ischemic stroke

Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro. With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs (p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions (p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs (p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression (p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

We aimed to explore the circulating microRNAs biomarkers in the acute stage following cerebral ischemia to earlier warn late-onset post-stroke depression (PSD). A total of 251 consecutive patients with acute ischemic stroke were recruited. They were divided into three groups depending on whether PSD had occurred at 2 weeks or 3 months since stroke: early-onset PSD, late-onset PSD, and non-depressed group. Microarray assay was conducted to identify the different expression profiles of plasma miRNAs. Comprehensive bioinformatics analysis for their integrating putative target genes was performed. The key miRNA was validated in a larger cohort and its function was further studied in ischemic mice brain. We screened three differentially expressed miRNAs in the late-onset PSD individuals, miR-140-5p and miR-221-3p were significantly upregulated while miR-1246 was downregulated. The bioinformatics analysis demonstrated that their predicted target genes were mainly enriched in axon development and Ras signaling pathway. Logistic regression analysis revealed that miR-140-5p was an independent risk factor for late-onset PSD (P = 0.017, OR = 2.313, 95%CI 1.158 to 4.617). The miR-140-5p expression on admission was significantly positively correlated with HDRS scores assessed at 3 months after stroke (P = 0.0007). The predictive value of miR-140-5p for late-onset PSD is 83.3% sensitivity and 72.6% specificity (AUC = 0.8127, P 0.0001). AAV-mediated overexpression of miR-140-5p decreased the protein level of IL1rap, IL1rapl1, VEGF, and MEGF10 in the ischemic mouse hippocampus and inhibited neurogenesis and capillary density. MiR-140-5p might be involved in the pathogenesis of late-onset PSD and used as a novel early warning biomarker.

OBJECTIVE This study aims to explore the function of blood microRNA-15a (miR-15a) in the pathogenesis of acute cerebral ischemia (AIS). METHODS Blood samples were collected from healthy control and AIS patients within 72 h after onset. A model of ischemia in human umbilical vein endothelial cells (HUVECs) was established through oxygen and glucose deprivation (OGD). MiR-15a in patients and in cells was measured using real-time quantitative polymerase chain reaction (qPCR). The predicted target of miR-15a such as interleukin-6 (IL-6) and insulin-like growth factors-1 (IGF-1) in plasma was detected by enzyme-linked immunosorbent assay (ELISA). The relations between blood miR-15a and stroke severity, stroke etiology, infarct location, stroke prognosis, predicted targets were analyzed by Statistical Product and Service Solutions (SPSS) software respectively. RESULTS Higher miR-15a levels were found in AIS patients and ischemic cells within 72 h, compared to control (p < 0.05). Receiver Operating Characteristic (ROC) analysis showed that blood miR-15a predicted stroke onset with 98.67% specificity. Blood miR-15a had a negative correlation with National Institutes of Health Stroke Scale (NIHSS) scores (r = -0.3695, p < 0.01). The AIS patients with increased miR-15a levels had a better prognosis. MiR-15a was up-regulated in anterior circulation infarction and small-artery atherosclerosis stroke. Plasma levels of IL-6 and IGF-1 were associated with blood miR-15a (r = -0.6051, 0.3231, p < 0.05, respectively). CONCLUSION Blood miR-15a associates with IL-6, IGF-1 and acute cerebral ischemia. It could serve as a potential diagnostic biomarker and therapeutic target for stroke.

Low-Xingouzui Formation II reservoir in the Xingou region of Jianghan Basin belongs to tight oil reservoir. By means of study about the geochemical characteristics of source rocks, lithology, physical property and pore structure characteristics, this paper confirms that the source rocks of Low-Xingouzui Formation II are mostly above medium in content of organic matter. The hydrocarbon source rocks are mainly of type II. The thermal maturity of most samples is immature-low mature. Dolomicrite and terrigenous clastic (intraclast) dolomite are the most favorable reservoir facies. The reservoir has mid to high porosity and extremely low permeability, and its space is dominated by dolomite dissolution with micro throat pore structure. This oil reservoir distributes widely and quasi continuous, while good conditions of petroleum formation exist. It could hopefully become new increasing point of Jianghan’s oil and gas output that has broad development prospects and studying value.

Objective To explore the associated factors of late-onset post-stroke depression (PSD). Methods A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. Results 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. Limitations The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. Conclusions The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD.