SWI and CTP fusion model based on sparse representation method to predict cerebral infarction trend.

Objective: SWI image signal is related to venous reflux disorder and perfusion defect. Computed tomography perfusion (CTP) contains perfusion information in space and time. There is a complementary basis between them to affect the prognosis of cerebral infarction. Methods: Sixty-six patients included in the retrospective study were designated as the training set. Effective perfusion indicator features and imaging radiomic features of the peri-infarction area on Susceptibility weighted imaging (SWI) and CTP modality images were extracted from each case. Thirty-three patients from the prospectively included group were designated as the test set of the machine learning model based on a sparse representation method. The predicted results were compared with the DWI results of the patients' 7-10 days review to assess the validity and accuracy of the prediction. Results: The AUC of the SWI + CTP integrated model was 0.952, the ACC was 0.909, the SEN was 0.889, and the SPE was 0.933. The prediction performance is the highest. Compared with the value of AUC: the SWI model is 0.874, inferior to the performance of the SWI + CTP model, and the CTP model is 0.715. Conclusion: The prediction efficiency of the changing trend of infarction volume is further improved by the correlation between the combination of the two image features.

Association of Bun/Cr ratio-based dehydration status with infarct volumes and stroke severity in acute ischemic stroke.

BACKGROUND: Only a few clinical research had previously investigated the dehydration status to predict the evolution of the ischemic core. The aim of this study is to clarify the association between blood urea nitrogen (BUN)/creatinine (Cr)ratio-based dehydration and infarct volume measured using DWI (Diffusion-weighted imaging) at admission in patients with AIS (Acute Ischemic Stroke). METHODS: We retrospectively recruited a total of 203 consecutive patients who were hospitalized through emergency or outpatient services within 72 h of acute ischemic stroke onset between October 2015 and September 2019. Stroke severity was measured by assessing the National Institutes of Health Stroke Scale (NIHSS) on admission. Infarct volume was measured using DWI with MATLAB software. RESULTS: In this study, 203 patients who met the study criteria were enrolled. Patients in the dehydration group (Bun/Cr ratio>15) had a higher median NIHSS score (6(IQR:4-10) VS. 5(3-7); P = 0.0015)and larger DWI infarct volume (1.55 ml (IQR:0.51-6.79) VS. (0.37 ml (0.05-1.22); P < 0.001) on admission compared with patients in normal group. Further, a statistically significant correlation was found between DWI infarct volumes and NIHSS score with nonparametric Spearman rank correlation (r = 0.77; P < 0.001). The median NIHSS scores for the DWI infarct volumes quartiles were 3 ml (IQR, 2-4), 5 ml (4-7), 6 ml (5-8), and12 ml (8-17) from lowest to highest. However, the second quartile group did not show any significant correlation with the third quartile group (P = 0.4268). Multivariable linear and logistic regression analyses were used to test dehydration (Bun/Cr ratio>15), representing a predictor of infarct volume and stroke severity. CONCLUSION: Bun/Cr ratio-based dehydration is associated with larger volumes of ischemic tissue measured using DWI and worse neurological deficit assessed by the NIHSS score in acute ischemic stroke.

Identification of the Hub Genes in Alzheimer's Disease.

PURPOSE: Alzheimer's disease (AD) is considered to be the most common neurodegenerative disease and also one of the major fatal diseases affecting the elderly, thus bringing a huge burden to society. Therefore, identifying AD-related hub genes is extremely important for developing novel strategies against AD. MATERIALS AND METHODS: Here, we extracted the gene expression profile GSE63061 from the National Center for Biotechnology Information (NCBI) GEO database. Once the unverified gene chip was removed, we standardized the microarray data after quality control. We utilized the Limma software package to screen the differentially expressed genes (DEGs). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs. Subsequently, we constructed a protein-protein interaction (PPI) network using the STRING database. RESULT: We screened 2169 DEGs, comprising 1313 DEGs with upregulation and 856 DEGs with downregulation. Functional enrichment analysis showed that the response of immune, the degranulation of neutrophils, lysosome, and the differentiation of osteoclast were greatly enriched in DEGs with upregulation; peptide biosynthetic process, translation, ribosome, and oxidative phosphorylation were dramatically enriched in DEGs with downregulation. 379 nodes and 1149 PPI edges were demonstrated in the PPI network constructed by upregulated DEGs; 202 nodes and 1963 PPI edges were shown in the PPI network constructed by downregulated DEGs. Four hub genes, including GAPDH, RHOA, RPS29, and RPS27A, were identified to be the newly produced candidates involved in AD pathology. CONCLUSION: GAPDH, RHOA, RPS29, and RPS27A are expected to be key candidates for AD progression. The results of this study can provide comprehensive insight into understanding AD's pathogenesis and potential new therapeutic targets.

Disparities in the Outcomes Following Ischemic Stroke Between the Floating Population and Indigenous Population of Shanghai.

Background and Purposes: Through this study, we hope to gain more insights into the differences in outcome following an ischemic stroke between the floating population and the indigenous population of Shanghai. Method: In this retrospective cohort study, we analyzed patients with first-ever acute ischemic stroke who were admitted to a comprehensive stroke center in the Minhang district, Shanghai, from January 1, 2019, to December 31, 2020. All patient's demographic data and medical histories were prospectively collected and they were followed up for at least 3 months. The Indigenous population of Shanghai was defined as patients with an identification number starting with 310. All others were treated as floating population. The primary outcome was defined as an unfavorable prognosis at 3 months, with a modified Rankin Scale (mRS) score above 1. Secondary outcomes included the use of emergency medical service (EMS), 3 h arrival rate, and endovascular therapy in eligible patients. Logistic regression analysis was applied to investigate the differences. Results: Finally, 698 patients with first-ever acute ischemic stroke were included (with mean age of 65.32 years, 74.6% men). Of these, 302 patients belonged to the floating population group. Indigenous populations with ischemic stroke were older than the floating population (68.26 years vs. 61.47 years, P < 0.001). The floating population was more likely to achieve favorable outcomes at 3 months compared with the indigenous population in multivariable logistic regression analysis [Odds ratio (OR): 0.49, 95% CI: 0.32-0.75, P = 0.001]. The use of EMS, 3 h arrival rate, and the application of endovascular therapy were comparable between the floating population and indigenous population (OR: 0.89, 95% CI: 0.62-1.27, P = 0.519; OR: 0.78, 95% CI: 0.56-1.09, P = 0.14; and OR: 0.82, 95% CI: 0.54-1.26, P = 0.365, respectively). Conclusion: Compared with the indigenous population, the floating population with the first-ever ischemic stroke was more likely to have a favorable outcome at 3 months.

Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke.

BACKGROUND: Stroke ranks as the third-leading cause of years of life lost worldwide. ANGPTL3 plays important roles in lipid metabolism, atherosclerosis, and occurrence of stroke. The purpose of this study was to evaluate associations of genetic variants in the ANGPTL3 gene with ischemic stroke (IS) risk. METHODS: A case-control study was conducted to evaluate the associations of tag single-nucleotide polymorphisms (SNPs) of the ANGPTL3 gene and risk of IS, as well as serum lipid levels. Dual-luciferase reporter assays in the HEK293T cell line was conducted to evaluate the promoter activity of ANGPTL3 rs6690733. RESULTS: We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13-1.59; P=0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64-0.93, P=0.007) were significantly associated with susceptibility to IS. Even corrected for Bonferroni adjustment, the two variants were still significant (0.007×4=0.028). Carriers of the minor allele of SNP rs6690733 had significantly higher levels of TC and LDL-C, while carriers of the minor allele of SNP rs12563308 had significantly lower levels of TC and LDL-C (all P<0.05). For rs6690733, the luciferase assay showed that promoter activity was significantly increased by 67% of plasmids containing the minor C allele compared with the major A allele in HEK293 cells. CONCLUSION: Our study revealed genetic variants of the ANGPTL3 gene could contribute to susceptibility to IS through participating in the regulation of lipid metabolism.

Identification of the biological affection of long noncoding RNA BC200 in Alzheimer's disease.

BC200 is a long noncoding RNA expressed at high levels in the Alzheimer's disease (AD), and blocking of BC200 by siRNA is assumed to be an effective method for various disease therapy. We have established an AD cell model overexpressing amyloid ß-peptide (Aß)1-42 to observe the effects of BC200 on the cell viability and apoptosis, and to investigate the associated underlying mechanisms. Efficient knockdown and overexpression of BC200 were established using BC200 siRNA and BC200 mimics, respectively. Cell viability following BC200 knockdown and overexpression was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide assay, and cell apoptosis was monitored by flow cytometry. We successfully established an AD cell model overexpressing Aß1-42 gene, and reported the results of change of BC200 on Aß1-42 levels. Knockdown of BC200 significantly suppressed b-site amyloid precursor protein-cleaving enzyme 1 (BACE1) expression, and overexpression of BC200 increased BACE1 expression. Besides, inhibition of BC200 significantly increased cell viability and reduced cell apoptosis in the AD model via directly targeting BACE1, which can be increased by overexpression of BC200. BC200 regulated AD cell viability and apoptosis via targeting BACE1, and it may be one of the putative target in AD development and provides potential new insights into genetic therapy against AD.

Autophagy inhibition sensitizes LY3023414-induced anti-glioma cell activity in vitro and in vivo.

PI3K-AKT-mTOR signaling is a valuable treatment target for human glioma. LY3023414 is a novel, highly-potent and pan PI3K-AKT-mTOR inhibitor. Here, we show that LY3023414 efficiently inhibited survival and proliferation of primary and established human glioma cells. Meanwhile, apoptosis activation was observed in LY3023414-treated glioma cells. LY3023414 blocked AKT-mTOR activation in human glioma cells. Further studies show that LY3023414 induced feedback activation of autophagy in U251MG cells. On the other hand, autophagy inhibition via adding pharmacological inhibitors or silencing Beclin-1/ATG-5 significantly potentiated LY3023414-induced glioma cell apoptosis. In vivo studies demonstrated that U251MG xenograft tumor growth in mice was suppressed by oral administration of LY3023414. Remarkably, LY3023414's anti-tumor activity was further augmented against the Beclin-1-silenced U251MG tumors. Together, our results suggest that targeting PI3K-AKT-mTOR cascade by LY3023414 inhibits human glioma cell growth in vitro and in vivo. Autophagy inhibition could further sensitize LY3023414 against human glioma cells.

Voltage-Dependent Anion Channel 1(VDAC1) Participates the Apoptosis of the Mitochondrial Dysfunction in Desminopathy.

Desminopathies caused by the mutation in the gene coding for desmin are genetically protein aggregation myopathies. Mitochondrial dysfunction is one of pathological changes in the desminopathies at the earliest stage. The molecular mechanisms of mitochondria dysfunction in desminopathies remain exclusive. VDAC1 regulates mitochondrial uptake across the outer membrane and mitochondrial outer membrane permeabilization (MOMP). Relationships between desminopathies and Voltage-dependent anion channel 1 (VDAC1) remain unclear. Here we successfully constructed the desminopathy rat model, evaluated with conventional stains, containing hematoxylin and eosin (HE), Gomori Trichrome (MGT), (PAS), red oil (ORO), NADH-TR, SDH staining and immunohistochemistry. Immunofluorescence results showed that VDAC1 was accumulated in the desmin highly stained area of muscle fibers of desminopathy patients or desminopathy rat model compared to the normal ones. Meanwhile apoptosis related proteins bax and ATF2 were involved in desminopathy patients and desminopathy rat model, but not bcl-2, bcl-xl or HK2.VDAC1 and desmin are closely relevant in the tissue splices of deminopathies patients and rats with desminopathy at protein lever. Moreover, apoptotic proteins are also involved in the desminopathies, like bax, ATF2, but not bcl-2, bcl-xl or HK2. This pathological analysis presents the correlation between VDAC1 and desmin, and apoptosis related proteins are correlated in the desminopathy. Furthermore, we provide a rat model of desminopathy for the investigation of desmin related myopathy.

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients.

METHODS: C5 rs17611 genetic variants were investigated in 494 IS patients and 330 control individuals .Ischemic stroke was classified into subtypes and patients were assessed 90 days post-stroke with the modified Rankin Scale to determine stroke outcome. RESULTS: The presence of C5 polymorphism was associated with the incidence of large artery atherosclerosis (LAA)-subtype IS (n =2 00; p = 0.031), which even persisted after adjustment for covariates (OR = 1.518; 95%CI = 1.093-2.018; p = 0.013). However, no association was found between genotypes and the severity and outcome of stroke (p = 0.978; p = 0.296). CONCLUSIONS: The C5 polymorphism might contribute to the risk of LAA-subtype IS independently of other known risk predictors.

Polymorphism of the complement 5 gene is associated with large artery atherosclerosis stroke in Chinese patients / O polimorfismo do gene C5 do complemento está associado a acidentes vasculares cerebrais de grandes artérias com aterosclerose em pacientes chineses

ABSTRACT The complement system has been confirmed to play an increasingly important role in ischemic stroke (IS). This study aimed to determine whether the single-nucleotide polymorphism of the complement 5 (C5) gene independently influences the occurrence, severity, and long-term outcome of IS in Chinese patients. Methods C5 rs17611 genetic variants were investigated in 494 IS patients and 330 control individuals .Ischemic stroke was classified into subtypes and patients were assessed 90 days post-stroke with the modified Rankin Scale to determine stroke outcome. Results The presence of C5 polymorphism was associated with the incidence of large artery atherosclerosis (LAA)-subtype IS (n =2 00; p = 0.031), which even persisted after adjustment for covariates (OR = 1.518; 95%CI = 1.093–2.018; p = 0.013). However, no association was found between genotypes and the severity and outcome of stroke (p = 0.978; p = 0.296). Conclusions The C5 polymorphism might contribute to the risk of LAA-subtype IS independently of other known risk predictors.

RESUMO Já se confirmou que o sistema do complemento exerce um papel cada vez mais importante nos acidentes vasculares cerebrais isquêmicos. Este estudo teve o objetivo de determinar se o polimorfismo de nucleotídeo único (SNP) do gene codificador do componente 5 (C5) influencia de forma independente a ocorrência, a severidade e o desfecho em longo prazo do acidente vascular cerebral isquêmico (AVCI) em pacientes chineses. Métodos Variantes genéticas rs17611 do C5 foram investigadas em 494 pacientes com AVCI e em 330 indivíduos controles. O AVCI foi classificado em subtipos e os pacientes foram avaliados 90 dias após o acidente vascular, através da Escala Modificada de Rankin (mRS), para determinação do desfecho do acidente. Resultados A presença de polimorfismo do C5 foi associada à incidência de AVCI do subtipo com aterosclerose de grandes artérias (AGA) (n = 200; p = 0,031), que persistiu mesmo após os ajustes de covariáveis (RP = 1,518; 95% IC = 1,093–2,018; p = 0,013). Entretanto, nenhuma associação foi observada entre os genótipos e a severidade ou o desfecho do acidente vascular (p = 0,978; p = 0,296). Conclusões O polimorfismo do C5 pode contribuir para o risco de AVCI do tipo com AGA, independentemente de outros riscos preditores conhecidos.

Cognitive dysfunction in type 2 diabetes patients accompanied with obstructive sleep apnea syndrome.

OBJECTIVE: To investigate cognitive dysfunction of type 2 diabetes patients accompanied with obstructive sleep apnea syndrome (OSAS), and to analyze its relevant characteristics. METHODS: Total 115 type 2 diabetes patients were divided into OSAS group (O group, n=83) and non-OSAS group (N group, n=32); Physical examination patients (C1 group, n=64) and OSAS patients without diabetes (C2 group, n=47) served as the control group. Apnea-hypopnea index (AHI), nocturnal lowest saturation of pulse oxygen (LSPO2) and simple mental state examination scale (MMSE) were evaluated. RESULTS: Among diabetes patients, patients with OSAS have lower glycated hemoglobin, platelet count, thrombocytocrit, MMSE score and lowest mean arterial oxygen than non-OSAS patients; cognitive dysfunction state and glycemic control of patients are related to their diabetic duration, and then along with increase of diabetic duration, glycemic control becomes poor, so that cognitive dysfunction becomes more and more obvious. CONCLUSION: Along with increased diabetic duration in type 2 diabetes accompanied with OSAS, glycemic control becomes poor, so that cognitive dysfunction more easily occurs. Meanwhile, coagulation function of blood system in OSAS patients with diabetes is impacted to some extent.

Association of thromboxane A2 receptor gene polymorphisms with cerebral infarction in a Chinese population.

Platelet aggregation is crucial for the development of cerebral infarction (CI) and it is markedly increased due to the binding of thromboxane A2 (TXA2) to its receptor (TXA2R). Therefore, TXA2R plays a central role in the pathogenesis of atherosclerosis and thrombosis. This study aimed to investigate the relationship between human TXA2R gene single nucleotide polymorphisms (SNPs) and non-cardiogenic CI in a Chinese cohort. Two SNPs, rs768963 and rs4523, located in the regulatory and coding regions of TXA2R gene, respectively, were examined in DNA samples from 407 Chinese patients with CI and 270 controls. 407 CI was categorized into subtypes using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. There was no significant association between rs4523 variants and CI. However, there was a significant difference in the overall distribution of genotypes and dominant/recessive models of rs768963 between CI and control groups. In addition, multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with total CI (P = 0.023), large artery atherosclerosis subtype (P = 0.009), small artery occlusion subtype (P = 0.044) after adjusting for confounding factors (odds ratio = 1.533, 1.918 and 1.573, respectively). We conclude that TXA2R rs768963 polymorphism is associated with CI in a Chinese population.