Development of a novel immune infiltration-related diagnostic model for Alzheimer's disease using bioinformatic strategies.

Background: The pathogenesis of Alzheimer's disease (AD) is complex and multi-factorial. Increasing evidence has shown the important role of immune infiltration in AD. Thus the current study was designed to identify immune infiltration-related genes and to explore their diagnostic value in AD. Methods: The expression data of AD patients were downloaded from the GEO database. The limma R package identified differentially expressed genes (DEGs) between AD and controls. The CIBERSORT algorithm identified differentially infiltrated immune cells (DIICs) between AD and controls. DIIC-correlated DEGs were obtained by Pearson correlation analysis. WGCNA was employed to identify DIIC-related modules. Next, LASSO, RFE, and RF machine learning methods were applied to screen robust DIIC-related gene signatures in AD, followed by the construction and validation of a diagnostic nomogram. Detection of the expression of related genes in the peripheral blood of Alzheimer's disease and healthy volunteers by RT-PCR. In addition, the CTD database predicted chemicals targeting DIIC-related gene signatures in the treatment of AD. Results: NK cells, M0 macrophages, activated myeloid dendritic cells, resting mast cells, CD8+ T cells, resting memory CD4+ T cells, gamma delta T cells, and M2 macrophages were differentially infiltrated between AD and controls. Pearson analysis identified a total of 277 DIIC-correlated DEGs between AD and controls. Thereafter, 177 DIIC-related genes were further obtained by WGCNA analysis. By LASSO, RFE and RF algorithms, CMTM2, DDIT4, LDHB, NDUFA1, NDUFB2, NDUFS5, RPL17, RPL21, RPL26 and NDUFAF2 were identified as robust gene signature in AD. The results of RT-PCR detection of peripheral blood samples from Alzheimer's disease and healthy volunteers showed that the expression trend of ten genes screened was consistent with the detection results; among them, the expression levels of CMTM2, DDIT4, LDHB, NDUFS5, and RPL21 are significantly different among groups. Thus, a diagnostic nomogram based on a DIIC-related signature was constructed and validated. Moreover, candidate chemicals targeting those biomarkers in the treatment of AD, such as 4-hydroxy-2-nonenal, rosiglitazone, and resveratrol, were identified in the CTD database. Conclusion: For the first time, we identified 10 immune infiltration-related biomarkers in AD, which may be helpful for the diagnosis of AD and provide guidance in the treatment of AD.

Predictors of favorable outcome and mortality after endovascular thrombectomy in young Chinese patients with large vascular occlusions.

Background: Endovascular thrombectomy (EVT) has evolved into the standard treatment for patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO). However, little information is available on the management of EVT in young patients with AIS-LVO in China. The purpose of this study was to assess the favorable outcomes and mortality rates after 90 days of EVT in young Chinese patients with AIS-LVO and their predictors. Methods: This retrospective study included young Chinese patients aged 18-50 years with AIS-LVO. The primary efficacy endpoint was the modified Rankin scale (mRS) score at day 90, and the primary safety endpoint was mortality within 90 days. Using univariate and multivariate logistic regression analyses, the associations between clinical, imaging, and procedure variables and favorable (mRS 0-2) outcomes or mortality at 90 days were analyzed. Results: A total of 113 patients were included in the study with a mean age of 43.1 ± 6.3 years. Symptomatic intracranial hemorrhage (sICH) occurred in 8 (7.1%) patients. Favorable functional outcomes (mRS 0-2) were recovered in 42.5% of patients at 3 months. After 90 days, the mortality rate was 32.3%. Multivariate analysis revealed that the increase in admission NIHSS score was associated with a lower probability of functional independence (aOR 1.08, 95% CI 1.02-1.15, p = 0.01 and aOR 1.01, 95% CI 1-1.01, p = 0.008, respectively) and a higher probability of death at 90 days (aOR 1.1, 95% CI 1.03-1.18, p = 0.007 and aOR 1.00, 95% CI 1-1.01, p = 0.021, respectively). Conclusion: This study demonstrate that EVT provides higher rates of arterial recanalization, rather than better favorable outcomes and lower risk of death at 3 months in young Chinese patients with AIS-LVO. Increased NIHSS scores on admission may be associated with poor patient prognosis.

Late delayed radiation-induced cerebral Arteriopathy by high-resolution magnetic resonance imaging: a case report.

BACKGROUND: Radiation therapy can cause cerebral arteriopahty, resulting in ischemic stroke. We document late-delayed cerebral arteriopathy by high-resolution magnetic resonance imaging (HR-MRI) in a middle aged man who had cranial irradiation 19 years earlier. CASE PRESENTATION: A 45-year-old man was diagnosed with frontal lobe glioma 19 years ago and was treated with radiation after surgical resection. He was admitted to our hospital with an acute cerebral infarction in November 8, 2017. Traditional MRI examination and HR-MRI (sagittal, reconstruction of coronal and axial) were performed at admission. He was treated with prednisone (30 mg/day) and clinical symptoms disappeared after 3 months by telephone follow-up. Our patient complained of dizziness and blurred vision and traditional MRI examination indicated acute ischemic stroke in temporal lobe and occipital lobe and microbleeds. In order to define the exact mechanism of stroke, blood tests, auto-immune screening and thrombophilia were performed and results were normal. Electrocardiography and echocardiography were negative and cardiogenic cerebral embolism was excluded. In cerebrospinal fluid (CSF) examination, level of albumin and IgG were elevated. HR-MRI showed vessel wall thickening in T1-weighted imaging, narrow lumen in proton density imaging and vessel wall concentric enhancement in contrast-enhanced T1- weighted imaging. Combined with radiotherapy history, the patient was diagnosed with radioactive vasculitis. CONCLUSION: Radiation-induced cerebrovascular damages could be a lasting progress, which we cannot ignore. HR-MRI can provide sensitive and accurate diagnostic assessment of radiation-induced arteritis and may be a useful tool for the screening of causes of cryptogenic stroke.

COL6A1 mutation leading to Bethlem myopathy with recurrent hematuria: a case report.

BACKGROUND: Collagen VI-related myopathies are a spectrum of muscular diseases with features of muscle weakness and atrophy, multiple contractures of joints, distal hyperextensibility, severe respiratory dysfunction and cutaneous alterations, attributable to mutations in the COL6A1, COL6A2, and COL6A3 genes. However, no case of collagen VI mutations with hematuria has been reported. We report a 14-year-old boy who had both Bethlem myopathy and recurrent hematuria and who carried a known de novo COL6A1 missense mutation c.877G > A (p.G293R). CASE PRESENTATION: The patient was a 14-year-old boy presenting with muscle weakness from 3 years of age without any family history. Six months before admission, he developed recurrent gross hematuria, three bouts in total, with the presence of blood clots in the urine. Next-generation sequencing of his whole-exome was performed. The result of sequencing revealed a de novo heterozygous G-to-A nucleotide substitution at position 877 in exon 10 of the COL6A1 gene. After treatment, the hematuria healed, but the muscle weakness failed to improve. CONCLUSIONS: Hematuria in Bethlem myopathy can be caused by COL6 mutations, which may be related to the aberrant connection between collagen VI and collagen IV.