Blood and CSF chemokines in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

OBJECTIVE: Chemokines, which are chemotactic inflammatory mediators involved in controlling the migration and residence of all immune cells, are closely associated with brain inflammation, recognized as one of the potential processes/mechanisms associated with cognitive impairment. We aim to determine the chemokines which are significantly altered in Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as the respective effect sizes, by performing a meta-analysis of chemokines in cerebrospinal fluid (CSF) and blood (plasma or serum). METHODS: We searched three databases (Pubmed, EMBASE and Cochrane library) for studies regarding chemokines. The three pairwise comparisons were as follows: AD vs HC, MCI vs healthy controls (HC), and AD vs MCI. The fold-change was calculated using the ratio of mean (RoM) chemokine concentration for every study. Subgroup analyses were performed for exploring the source of heterogeneity. RESULTS: Of 2338 records identified from the databases, 61 articles comprising a total of 3937 patients with AD, 1459 with MCI, and 4434 healthy controls were included. The following chemokines were strongly associated with AD compared with HC: blood CXCL10 (RoM, 1.92, p = 0.039), blood CXCL9 (RoM, 1.78, p < 0.001), blood CCL27 (RoM, 1.34, p < 0.001), blood CCL15 (RoM, 1.29, p = 0.003), as well as CSF CCL2 (RoM, 1.19, p < 0.001). In the comparison of AD with MCI, there was significance for blood CXCL9 (RoM, 2.29, p < 0.001), blood CX3CL1 (RoM, 0.77, p = 0.017), and blood CCL1 (RoM, 1.37, p < 0.001). Of the chemokines tested, blood CX3CL1 (RoM, 2.02, p < 0.001) and CSF CCL2 (RoM, 1.16, p = 0.004) were significant for the comparison of MCI with healthy controls. CONCLUSIONS: Chemokines CCL1, CCL2, CCL15, CCL27, CXCL9, CXCL10, and CX3CL1 might be most promising to serve as key molecular markers of cognitive impairment, although more cohort studies with larger populations are needed.

Optical design of an Offner coded aperture snapshot spectral imaging system based on dual-DMDs in the mid-wave infrared band.

With the advantages of flexible encoding and high frame rate, the digital micromirror devices (DMD) have been used as a binary encoding mask in the coded aperture snapshot spectral imaging (CASSI) systems. But the use of DMD will cause the image plane to tilt at a specific angle, so it is almost impossible to realize the strict matching between the optical system of CASSI and the cold stop of the infrared focal plane array in the mid-wave infrared band. In this paper, a CASSI system with two DMDs based on the Offner spectrometer is proposed to solve the above problem. The concept and working principle are described in detail. Under the premise of the matching optical parameters, the telescopic system, Offner spectroscopic system and microscopic system are designed independently. Then the integrated optimization design method is adopted, and the aberration of the microscopic system is used to offset the astigmatic aberration of the Offner spectroscopic system, and the imaging quality of the system is improved. The results of performance measurements confirm that the system has desirable spatial resolution and spectral response functions. Thus, the concept and optical design of the proposed system are verified to be effective and valuable.

Association of interleukin-6 methylation in leukocyte DNA with serum level and the risk of ischemic heart disease.

Background Interleukin-6 (IL-6), a multifunctional cytokine, plays an important role in the development of ischemic heart disease (IHD), and DNA hypomethylation of 2 CpGs, located downstream in the proximity of the IL-6 gene promoter, has been associated with risk factor for IHD. This study was to examine the association of blood leukocyte DNA methylation of the 2 CpGs in IL-6 with the risk of IHD and the serum IL-6 level. Methods IL-6 methylation levels of 582 cases and 673 controls were measured using the bisulfite pyrosequencing technology. Serum level of IL-6 was measured using enzyme-linked immunosorbent assay. Results The IL-6 methylation was significantly lower in IHD cases than in the controls, irrespective of CpG site. After multivariate adjustment, lower (< median) average IL-6 methylation was associated with an increased risk of IHD (OR 1.57, 95% CI 1.22-2.02, p < 0.001). Average IL-6 methylation level was inversely associated with serum IL-6 level (ß = -1.02 pg/mL per increase in IL-6 methylation, p = 0.002) among IHD cases. This significant relationship was not observed among controls. Conclusions DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of IHD. IL-6 demethylation may upregulate its expression, whereby exerting its risk effect on the development of IHD.

Determinants of Disease Outcome in Patients with Drainage of Aortic Root Abscess Caused by Infective Endocarditis.

The aim of this study was to investigate the factors that determine disease outcome in patients with drainage of aortic root abscess caused by infective endocarditis. Data from 27 patients who were treated for aortic root abscess due to infective endocarditis were analyzed. Nineteen patients survived for more than 3 years after discharge, seven patients died within 1 month after the surgery, and one patient died during the surgery. Based on survival or terminal outcome, patients were divided into two groups. There was no significant difference between surviving or dead patients in terms of age or gender. Other factors, such as disease course, surgery, cardiac function, pathology, pathogenic microorganisms, complications, and nosocomial infections were significantly different between patient groups and appear to be associated with disease outcome. Patients' deaths can be reduced through targeted clinical therapy.

Association of copy number loss of CDKN2B and PTCH1 with poor overall survival in patients with pulmonary squamous cell carcinoma.

BACKGROUND AND PURPOSE: Although lung cancer is the leading cause of cancer deaths worldwide, reliable markers allowing prediction of patient survival at the time of initial diagnosis are still lacking. Copy number alterations (CNAs) in tumor tissue DNA have been associated with tumorigenesis and malignant progression. We aimed at identification of gene-level CNAs with prognostic value for survival in pulmonary squamous cell carcinoma (SCC). METHODS: The CNA status of a panel of 44 genes was analyzed by high-resolution array comparative genomic hybridization (CGH) in 49 SCC samples. Overall survival information (median follow-up, 40 months) for the patients was collected and used to assess outcome correlations with gene CNAs. RESULTS: Survival analysis showed that both CDKN2B loss and PTCH1 loss were associated with poor survival (both P < .001, log-rank test). Multivariate Cox analysis, including CDKN2B loss and PTCH1 loss as well as age, sex, cigarette smoking status, tumor size, tumor differentiation, and TNM stage showed that CDKN2B loss (hazard ratio [HR], 17.88; 95% confidence interval [CI], 4.40-72.67; P < .001) and PTCH1 loss (HR, 10.81; 95% CI, 1.92-60.98; P = .007) were independent prognostic factors for poor survival. In addition the PTCH1 loss was more frequently found in moderately or poorly differentiated tumors than in well-differentiated tumors (P = .007). CONCLUSION: These findings suggest that 2 genes of loss, CDKN2B and PTCH1, are associated with poor overall survival in patients with SCC of the lung and may be useful as prognostic markers.

The relationship between EGFR gain and VHL loss in lung adenocarcinoma and poor patient survival.

BACKGROUND: The prognosis of lung cancer remains poor and clinically applicable prognostic markers have not yet been satisfactory identified. Several chromosomal copy number alterations (CNAs) have been associated with metastasis, relapse, and survival of patients with lung cancer; however, no study has focused exclusively on identifying CNAs at a gene level. The aim of this study was to identify genes whose CNAs are associated with survival of patients with lung adenocarcinoma. METHODS: The CNA status of a panel of 48 genes was detected by high-resolution array comparative genomic hybridization in 56 lung adenocarcinoma samples. The follow-up time of these patients was 8.5-65.7 months. The gene CNAs were analyzed for their association with patient survival. RESULTS: Cox univariate regression analysis revealed that EGFR gain (hazard ratio (HR) 3.84, 95% confidence interval (CI) 1.62-9.10), VHL loss (HR 4.56, 95% CI 1.85-11.27) and WWOX loss (HR 4.14, 95% CI 1.60-10.69) were each associated with poor survival. Multivariate analyses including EGFR gain, VHL loss and WWOX loss, as well as the clinicopathological variables such as age, sex, tumor size, tumor differentiation and TNM stage showed that EGFR gain (HR 4.63, 95% CI 1.69-12.7) and VHL loss (HR 4.82, 95% CI 1.41-16.43) were independent prognostic factors for poor survival, whereas WWOX loss lost statistical significance. CONCLUSION: These findings suggest that EGFR gain and VHL loss are associated with poor overall survival for lung adenocarcinoma patients and may be used as prognostic markers.