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This study aimed to evaluate the effect of Wogonoside (Wog), a flavonoid monomer, on hyperlipidemia and explore its possible mechanisms. APOE -/- mice were used to establish the animal model of hyperlipidemia by feeding the high-fat diet (HFD). The serum level of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA), oil red O staining, and real-time PCR assay. The oxidative stress was measured by ELISA assay. Immunoblot assay and ELISA assay were used to detect the mechanism of Wogonoside on hyperlipidemia. We found that Wogonoside ameliorated lipid metabolism disorders in ApoE -/- mice induced by HFD (P

To evaluate the intraocular pressure (IOP)-lowering effect of the combination of phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes of advanced primary angle-closure glaucoma (PACG) with cataract.Multicenter observational study.We enrolled 83 eyes of 83 patients with advanced PACG who received combined PEI+GSL+GT at 8 ophthalmic institutes. Each patient was assessed before treatment and at 1, 7 days, 1, 3, 6, and 12 months postsurgery. The criteria for complete success were IOP within 6 to 18 mm Hg and at least 20% of reduction in IOP from baseline without ocular hypotensive medications or reoperation. The definition of qualified success was similar to that of complete success, except for the need for ocular hypotensive medications. The potential prognostic factors for surgical success were investigated using a multivariate logistic model.All participants completed 1 year of follow-up. Complete and qualified success were achieved in 74 (89.1%) and 79 (95.2%) of 83 eyes, respectively. The mean preoperative and postsurgical IOPs were 27.4±7.3 and 14.2±2.6 mm Hg, respectively. Participants used an average of 2.0 and 0.3 types of ocular hypotensive medications before and after surgery, respectively. The chief complications included hyphema (n=9), IOP spike (n=9), and corneal edema (n=8). None of the eyes required reoperation or developed vision-threatening complications. Multivariate analysis showed that older age was associated with a higher probability of complete success (odds ratio=1.13; 95% CI: 1.02-1.25; P=0.020).The 1-year results of combination of PEI+GSL+GT in treating advanced PACG cases with cataract appear to be safe and effective. Further large-scale multination and multicenter studies are warranted.

For the problems of premature death of cluster head nodes, short network life cycle and fast energy consumption in hierarchical clustering LEACH protocol in wireless sensor networks, an improved routing protocol K-means LEACH distance optimization algorithm based on LEACH is proposed in this paper. The improved routing algorithm takes into account the problems such as random selection of cluster heads and tedious calculation of distance formula in LEACH algorithm, so K-means clustering algorithm is introduced. The specific scheme is to first divide the data into K classes, then select the appropriate cluster heads, and introduce the Chebyshev distance formula on the basis of K-means clustering algorithm. From the comparative analysis of the simulation results, the K-means LEACH distance optimization algorithm compared to the original LEACH algorithm wireless network node life cycle by 64%, node energy consumption by 26%, which is conducive to improving the stability of WSN, reducing node energy consumption and extending the network survival time.

Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3,105 participants were included in the final analysis; 1,558 (50.18%) participants received ezetimibe and statin combination therapy and 1,547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients co-administered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (p < 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.

Artemisia argyi is widely distributed in Asia, and it often becomes the dominant population in the field because of its strong ecological niche competitiveness. Allelochemicals secreted by plants are generally considered an important reason for their dominance in ecological competition. In this study, the allelochemicals in A. argyi were screened by a series of experiments and their mechanisms were explored via transcriptomics. First, the inhibitory effects of A. argyi on Echinochloa crusgalli, Setaria viridis, Portulaca oleracea and Amaranthus retroflexus were evaluated. Then, we carried out a qualitative and quantitative analysis of the chemical composition of the aqueous extract of A. argyi to screen for potential allelochemicals that can inhibit weed growth. Four potential allelochemicals were quantified: neochlorogenic acid (5-CQA), chlorogenic acid (3-CQA), cryptochlorogenic acid (4-CQA), and caffeic acid (CA). Coincidentally, their allelopathic effects on weeds seemed to be identical to their content, in the order CA>4−CQA>5−CQA>3-CQA. These findings suggested that CA might be the main allelopathic compound in the aqueous extract of A. argyi. Subsequently, the allelopathic effect and molecular mechanism of CA on S. viridis leaves were investigated. The physiological results showed that CA significantly induced reactive oxygen species (ROS) production, led to malondialdehyde (MDA) accumulation, and disrupted enzyme activities (POD, SOD, CAT) in S. viridis leaves. Moreover, transcriptome results revealed that CA inhibited S. viridis growth by downregulating multiple genes involved in gibberellin (GA) and phytoalexin biosynthesis and Mitogen-activated protein kinase (MAPK) signaling pathways. In addition, differentially expressed genes (DEGs) related to the biosynthesis and signaling pathways of phytohormones were verified by Quantitative Real-Time PCR (RT-qPCR). Taken together, this study may be the first to identify allelochemicals and explore their molecular mechanism about A. argyi. Importantly, the ecological advantages of A. argyi could be applied to ecological regulation and the development of botanical herbicides.

Background Peritoneal dialysis (PD) can be associated with abnormal cardiac structure and function and increased mortality risk. Therefore, in this study, we analyzed the cardiac structure and function dynamic changes using echocardiography during the first 2 years of PD therapy. We also assessed its associations with all-cause mortality risk after 2 years of follow-up. Methods End-stage renal disease (ESRD) patients that have started PD from 2011 to 2017, and had echocardiography at baseline and years 1 and 2, were included in this study. Echocardiographic parameters were compared between baseline and year 2. Multivariable Cox models were used to estimate the association between echocardiographic parameters changes and all-cause mortality risk. Results We finally enrolled 72 PD patients in this study. The mean right ventricular diameter (RVD) increased from baseline (18.31 mm) to year 1 (18.75 mm) and year 2 (19.65 mm). We also observed a significant decrease in cardiac output (CO) between baseline and year 2. Additionally, a slight decrease trend in ejection fraction (EF) was observed. Finally, every 1 % increase in RVD was associated with a 68.2 % higher mortality risk after dialysis (HR, 1.682; 95 % CI, 1.017–2.783). Conclusions Our results demonstrated a susceptibility for deteriorated right cardiac structure and function during the first 2 years of PD treatment. Also, higher all-cause mortality risk was observed after 2 years of PD. Altogether, these results highlighted the need for additional focus on regular echocardiographic examinations during long-term PD management. Trial registration The PD-CRISC cohort, registered with the Chinese Clinical Trial Registry (ChiCTR1900023565).

Summary The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different signaling layers in animals with different genetic backgrounds is lacking. Here, we applied systems approaches to investigate the effect of UPRmt induced by doxycycline (Dox) on transcriptome, proteome, and lipidome in two genetically divergent worm strains, named N2 and CB4856. From the integrated omics datasets, we found that Dox prolongs lifespan of both worm strains through shared and strain-specific mechanisms. Specifically, Dox strongly impacts mitochondria, upregulates defense response, and lipid metabolism, while decreasing triglycerides. We further validated that lipid genes acs-2/20 and fat-7/6 were required for Dox-induced UPRmt and longevity in N2 and CB4856 worms, respectively. Our data have translational value as they indicate that the beneficial effects of Dox-induced UPRmt on lifespan are consistent across different genetic backgrounds through different regulators., Graphical abstract, Highlights • Dox extends lifespan of N2 and CB4856 via shared and strain-specific mechanisms • Dox controls mitochondria, defense responses, and lipid metabolism in both strains • Dox-mediated longevity requires acs-2/20 in N2 and fat-7/6 in CB4856 worms, Chronobiology; Proteomics; Transcriptomics

The mitochondrial unfolded protein response (UPRmt) is a promising pharmacological target for aging and age-related diseases. However, the integrative analysis of the impact of UPRmt activation on different layers of signaling in animals with a different genetic background is lacking. In this study, we applied systems approaches to investigate the effect of UPRmt induced by administering doxycycline (Dox) on transcriptome, proteome, lipidome, and metabolome in two genetically divergent C. elegans strains. We found that Dox prolongs lifespan of both worm strains through pathways in both shared and strain-specific manners. From the integrated omics datasets, we observed a strong impact of Dox on mitochondrial functions, detected upregulated defense response and lipid metabolism, identified decreased triglycerides and lowered metabolome profiles in both strains. This conserved phenomic footprint has great translational value as it indicates that the beneficial effects of Dox-induced UPRmt on health and lifespan are consistent across different genetic backgrounds.

We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity., Graphical Abstract, Highlights · We surveyed biomolecules in 102 COVID-19 and 26 non-COVID-19 patient blood samples · We found 219 biomolecules strongly associated with COVID-19 status and severity · We observed pronounced dysregulation of lipid transport and neutrophil degranulation · Our resource of measurements and patient data is located at https://covid-omics.app, Leukocyte mRNA expression and plasma protein, metabolite, and lipid levels were measured in 102 COVID-19 and 26 non-COVID patient samples. 219 diverse biomolecules were strongly associated with COVID-19 status and severity and pointed to dysregulation of processes related to lipid transport, blood coagulation, acute phase response, endotheliopathy, and neutrophil degranulation in this disease.

Cyanobacteria blooms are crucial environmental issues by threatening both aquatic ecosystem and human health. A biomass by-product with antimicrobial activity, pyroligneous acid (PA) was tested for its suitability for removal of the cyanobacteria Microcystis aeruginosa (M. aeruginosa) in this work. Results show that the removal efficiency could reach up to 90% in the presence of 0.45% of PA and the inhibition to M. aeruginosa growth could extend to at least 40 days. The removal mechanism was studied. Both organic acids and phenols are functional content in M. aeruginosa removal and acetic acid is the most important one. Zeta potential analysis and morphology study show that the damage of cells dominates the flocculation and sedimentation of M. aeruginosa under low PA concentration (0.7%), and increasing PA (≥0.7%) resulted in a trend of zeta potential to zero, thus removing any "shield" and triggering flocculation. Finally, study on the phenols residual after M. aeruginosa treatment shows that it could be close to 0 in 70 h. Therefore, this work proposes a possible method for world-wide treatment of cyanobacteria bloom and a new way for further utilization of PA.

Background Simultaneous bilateral femoral neck fractures are extremely rare without obvious injury. Herein, we report the case of a patient on dialysis presenting with bilateral femoral neck fractures, which is a condition with high complication and mortality rates according to a review of the pertinent literature. Case presentation We report the case a 47-year-old female with a history of 8 years of haemodialysis due to polycystic kidney disease who presented with bilateral hip pain during walking. The clinical history and results of physical and radiographic examinations of this patient are shown. Single-stage bilateral hemiarthroplasty was performed after a multidisciplinary team consultation. Three days after the operation, she could ambulate with a walker. The woman gradually regained her previous ability to walk over 6 months after surgery. Conclusions A multidisciplinary team consultation for perioperative management is necessary and effective in patients on dialysis. Early diagnosis with prompt surgical treatment could lead to favourable recovery.

Background Sjögren syndrome (SS) is a rare disease in pediatrics, and little attention has been paid to the clinical feature in these patients. To date, there are few cases concern about neurological and nephrological disorders in childhood Sjögren syndrome. We describe a case of Sjögren syndrome in a 12-year-old girl who developed neurological disorders and interstitial nephritis and review the literature currently available on this topic. Case presentation A 12-year-old girl was admitted to our hospital for arthritis and glucosuria. She was required to do labial gland and renal biopsy, because the positive for anti-nuclear antibody and anti-Sjögren syndrome B (anti-SSB) antibody. Then the biopsy was performed revealing the lymphocytic infiltrate in the small area and renal tubular interstitial damage,thus the diagnosis of Sjögren syndrome with tubular interstitial damage was made. Three months later, she presented again with headache, fever, nausea, vomiting and was recovered without drug therapy. Based on the patient’s medical history, laboratory and imaging examination, and treatment, we speculate that the disorders of the nervous system were caused by the Sjögren syndrome. The girl has stable renal function and no residual nervous system damage in the next 1.5 years, but she underwent low dose prednisone therapy because of persistent renal glucosuria. Conclusions Nephrological disorders and neurological involvement are rare manifestations of Sjögren syndrome in children, and rarely presented as the initial symptoms. It should be suspected in children presenting with unexplained renal diseases, neurological abnormalities, or unexplained fever. Although there is no guidelines on the diagnosis and treatment of children Sjögren syndrome are currently available, early recognition and the appropriate treatment of renal damage and neurologic involvement would improve prognosis and prevent complications.

Microorganisms in the rhizosphere of wetland plants can have a significant impact on phosphorus (P) interception. We investigated the seasonal pattern of microbial community structure and its relationship with different P forms in the rhizosphere of three plants Scirpus planiculmis, Zizania latifolia, and Phragmites australis from the Yeyahu Wetland, China. Chloroform fumigation-extraction was used to determine the soil microbial biomass P (SMBP) and phospholipid fatty acids (PLFA) were used to characterize microbial community composition. P fractions in rhizosphere soil samples were also observed using sequential chemical fractionation. Results showed that the average total PLFA (TPLFA) contents of rhizosphere soils ranged from 34.9 to 40.7nmol·g-1 and were highest in summer. Bacteria were predominant in the rhizospheres of all three plants, accounting for >63% of TPLFA. Aerobic bacteria, represented by 16:0 PLFA, were most abundant. Both organic P (OP) and inorganic P (IP) accumulated in the rhizosphere during the winter die-back phase. Furthermore, both TPLFA and bacterial PLFA decreased with increases in highly resistant OP (HR-OP), occluded P (Oc-P) and Calcium-bound P (Ca-P). This suggests that bacteria play an important role in P transformation and can make use of various P forms. We also found that SMBP was significantly negatively correlated with labile OP (L-OP), moderately labile OP (ML-OP) and HR-OP, reflecting a high degree of cross correlation between SMBP and the PLFA indices.

// Yunyun Zhu 1 , Yiguo Qiu 1 , Hongsong Yu 1 , Shenglan Yi 1 , Wencheng Su 1 , Aize Kijlstra 2 and Peizeng Yang 1 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, China 2 University Eye Clinic Maastricht, Maastricht, The Netherlands Correspondence to: Peizeng Yang, email: peizengycmu@126.com Keywords: DNA methylation, Behcet’s disease, CD4 + T cell Received: May 19, 2017 Accepted: June 12, 2017 Published: July 22, 2017 ABSTRACT The pathogenesis of Behcet’s disease (BD) remains poorly understood. The purpose of this study was to investigate whether an aberrant DNA methylation of transcriptional and inflammatory factors, including TBX21, GATA3, RORγt, FOXP3, IFN-γ, IL-4, IL-17A and TGF-β , in CD4 + T confers risk to BD. We found that the promoter methylation level of GATA3, IL-4 and TGF-β was significantly up-regulated in active BD patients and negatively correlated with the corresponding mRNA expression. The mRNA expression of GATA3 and TGF-β was markedly down-regulated in active BD patients compared to healthy individuals. Treatment with corticosteroids and cyclosporine (CsA) resulted in a decrease of the methylation level of GATA3 and TGF-β in inactive BD patients. Our results suggest that an aberrant DNA methylation of GATA3 and TGF-β is associated with their mRNA expression and participates in the pathogenesis of BD.

PURPOSE. We investigated the role of promoter methylation of transcriptional and inflammatory factors, including TBX21, GATA3, ROR gamma t, FOXP3, IFN-gamma, IL-4, IL-17A, and TGF-beta in the development of Vogt-Koyanagi-Harada (VKH) disease.METHODS. The promoter methylation levels were detected by the Sequenom MassARRAY system in CD4(+) T cells that were separated from 20 healthy individuals and 32 VKH patients (20 in the active stage without medication, 12 in inactive stage with medication). The mRNA expression level of GATA3, IL-4, and TGF-b in CD4(+) T cells was analyzed by real-time RT-PCR.RESULTS. The promoter methylation levels of GATA3, IL-4, and TGF-b were significantly higher in active VKH patients than in healthy individuals (P CONCLUSIONS. Our findings suggest that promoter hypermethylation of GATA3 and TGF-b in CD4(+) T cells confers risk to VKH disease in Han Chinese.

Background: Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behc,et's disease (BD), this has not yet led to a breakthrough in the management of BD.Objective: This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies-identified nearly positive P values (5.0 x 10(-8) Methods: A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA.Results: The results showed that significantly higher frequencies of the IL23R-IL12RB2/rs924080 TT genotype (P = 2.03 x 10(-8); odds ratio [OR] = 1.50), IL23R-IL12RB2/rs12141431 CC genotype (P = 2.18 x 10(-8); OR = 1.53), IL10/rs1800871 TT genotype (P = 5.88 s 10(-8); OR = 1.47), and IL10/rs3024490 TT genotype (P = 2.80 x 10(-5); OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers.Conclusions: Our findings not only confirmed the association of IL10/rs1800871 and IL23R-IL12RB2/rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.

Objective The aetiology of Behçet’s disease (BD), known as a systemic vasculitis, is not completely understood. Increasing evidence suggests that aberrant DNA methylation may contribute to the pathogenesis of BD. The aim of this epigenome-wide association study was to identify BD-associated methylation loci in Han Chinese. Methods Genome-wide DNA methylation profiles were compared between 60 BD patients and 60 healthy controls using the Infinium Human Methylation 450 K Beadchip. BD-associated methylation loci were validated in 100 BD patients and 100 healthy controls by pyrosequencing. Gene expression and cytokine production was quantified by real-time PCR and ELISA. Results A total of 4332 differentially methylated CpG sites were associated with BD. Five differentially methylated CpG sites (cg03546163, cg25114611, cg20228731, cg23261343 and cg14290576) revealed a significant hypomethylation status across four different genes (FKBP5, FLJ43663, RUNX2 and NFIL3) and were validated by pyrosequencing. Validation results showed that the most significant locus was located in the 5’UTR of FKBP5 (cg03546163, P = 3.81E-13). Four CpG sites with an aberrant methylation status, including cg03546163, cg25114611, cg23261343 and cg14290576, may serve as a diagnostic marker for BD (area under the receiver operating curve curve = 83.95%, 95% CI 78.20, 89.70%). A significantly inverse correlation was found between the degree of methylation at cg03546163 as well as cg25114611 and FKBP5 mRNA expression. Treatment with a demethylation agent, 5-Aza-2’-deoxycytidine resulted in an increase of FKBP5 mRNA expression and a stimulated IL-1β production. Conclusion Our findings suggest that aberrant DNA methylation, independently of previously known genetic variants, plays a vital role in the pathogenesis of BD. Trial registration Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR-CCC-12002184.

Hepatitis B virus X protein (HBx) has been previously demonstrated to be associated with the regulation of cell proliferation; however, the exact mechanisms underlying this effect remain unclear. The present study aimed to investigate the regulatory mechanism of HBx on the cycle progression of primary renal tubular epithelial cells. Primary renal tubular epithelial cells of Sprague Dawley (SD) rats were separated and cultured. The morphology of cultured cells was characterized by immunohistochemical analysis and the results demonstrated that primary renal tubular epithelial cells with the expected morphology and distribution were successfully separated and cultured from SD rats. HBx gene pcDNA3.1/myc vector and empty vector were constructed and transfected into cells as HBx and empty groups, respectively. Following transfection, the mRNA and protein levels of HBx, cyclin A, cyclin D1 and cyclin E in cells were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that following HBx gene transfection, the mRNA and protein levels of HBx, cyclin A, cyclin D1 and cyclin E in cells were significantly upregulated, compared with the empty control group (P

The key transcription factors of T helper cell subpopulations, including T-bet, GATA3, RORγt, and Foxp3 are involved in various autoimmune diseases. Whether methylation of these master transcription factors is associated with the development of experimental autoimmune uveitis (EAU) and the possible epigenetic regulatory mechanisms involved has however not yet been addressed. In our study, significant methylation changes in both Tbx21 and Rorc were observed in one CpG site in the retinas of EAU mice. Two CpG sites of Tbx21 and one CpG site of Rorc showed significant dynamic methylation changes in the RPE-choroid complex during EAU. The mRNA expressions of Tbx21 and Rorc in both the retinas and RPE-choroid complexes correlated with the methylation changes at the various time points during EAU development. The methylation changes were associated with the production of the Th1/Th17 cells’ signature cytokines, IFN-γ and IL-17. Dynamic changes in mRNA expression of DNA methyltransferases (DNMT1) were also noted, which may be related to the observed methylation changes of these genes. The present study provides evidence that DNA methylation of Tbx21 and Rorc may be associated with the development of EAU. DNMT1 activation may have an important effect on regulating DNA methylation dynamics.

// Yiguo Qiu 1 , Yunyun Zhu 1 , Hongsong Yu 1 , Shenglan Yi 1 , Wencheng Su 1 , Qingfeng Cao 1 , Gangxiang Yuan 1 , Aize Kijlstra 2 and Peizeng Yang 1 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China 2 University Eye Clinic Maastricht, Maastricht, The Netherlands Correspondence to: Peizeng Yang, email: peizengycmu@126.com Keywords: DNA methylation, interferon regulatory factor 8, Behcet’s disease, dendritic cells Received: February 15, 2017 Accepted: March 28, 2017 Published: April 19, 2017 ABSTRACT Aberrant methylation of interferon regulatory factor 8 (IRF8) has been noted in various tumors. IRF8 has also been reported to be involved in many autoimmune diseases, including Behcet’s disease (BD). However, the methylation status of IRF8 in BD has not been reported. To address this issue, we investigated whether the degree of methylation of IRF8 in dendritic cells (DCs) plays a role in the development of BD. We found a lower mRNA expression and a higher methylation level of IRF8 in active ocular BD patients as compared to normal subjects and inactive patients. Treatment with a demethylation agent, 5-Aza-2’-deoxycytidine (DAC) resulted in an increase of mRNA expression and a reduction of the IRF8 methylation level. It also down-regulated the expression of the co-stimulatory molecules CD86, CD80, CD40, and reduced the production of IL-6, IL-1β, IL-23 and IL-12. An inhibition of Th1/Th17 responses was observed as evidenced by a decreased production of IFN-γ, IL-17, and a reduction of IFN-γ/IL-17- producing CD4 + T cells following treatment with DAC. This study shows that active ocular BD patients have an aberrant IRF8 methylation status. These findings suggest that epigenetic control of IRF8 expression may offer a future target in the treatment of ocular BD.

Aberrant methylation change of IRF8 confers risk to various tumors, and abnormal expression of IRF8 is involved in many autoimmune diseases, including ocular Behcet’s disease. However, whether the methylation change of IRF8 is associated with Vogt-Koyanagi-Harada (VKH) disease remains unknown. In the present study, we found a decreased IRF8 mRNA expression in association with a higher methylation level in monocyte-derived dendritic cells (DCs) from active VKH patients compared with the normal and inactive subjects. DCs incubated with cyclosporin a (CsA) or dexamethasone (DEX) showed a lower methylation and higher mRNA expression of IRF8 in active VKH patients. A demethylation reagent, 5-Aza-2′-deoxycytidine (DAC) showed a notable demethylation effect as evidenced by increasing the mRNA expression and reducing the methylation level of IRF8. It also suppressed the Th1 and Th17 responses through down-regulating the expression of co-stimulatory molecules (CD86, CD80, CD40), and reducing the production of pro-inflammatory cytokines (IL-6, IL-1β, IL-23, IL-12) produced by DCs. These findings shows that hypermethylation of IRF8 in DCs confers risk to VKH disease. Demethylation of IRF8 may offer a novel therapeutic strategy protect against VKH disease.

The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P

Background A number of researches have evaluated the association between the ABCB1 polymorphism and the lipid-lowering response of statins, but the results have been inconclusive. To examine the lipid-lowering efficacy and safety associated with the ABCB1 C3435T polymorphism in hypercholesterolemic patients receiving statin, all available studies were included in this meta-analysis. Methods A systematic search for eligible studies in the Cochrane library database, Scopus and PubMed was performed. Articles meeting the inclusion criteria were comprehensively reviewed, and the available data were accumulated by the meta-analysis. Results The results indicated that the comparisons of CC+CT vs. TT were associated with a significant elevation of the serum HDL-C levels after statin treatment (CC+CT vs. TT: MD, 2.46; 95 % CI, 0.36 to 4.55; P = 0.02), and the ABCB1 C3435T variant in homozygotes was correlated with decreases in LDL-C (CC vs. TT: MD, 2.29; 95 % CI, 0.37 to 4.20; P = 0.02) as well as TC (CC vs. TT: MD, 3.05; 95 % CI, 0.58 to 5.53; P = 0.02) in patients treated with statin. However, we did not observe a significant association in the TG group or an association between other genetic models serum lipid parameters. In addition, statin treatment more than 5 months led to a higher risk of muscle toxicity. Conclusions The evidence from the meta-analysis demonstrated that the ABCB1 C3435T polymorphism may represent a pharmacogenomic biomarker for predicting treatment outcomes in patients on statins and that statin treatment for more than 5 months can increase the risk of myopathy.

Motion blur is very common in the blurred images, and rotating motion blur is one kind of special and general fuzzy form. Based on the principles of linear motion blur restoration, to change the rotary motion into linear motion blur , this paper propose a regularization recovery mode which is equipped with a norm l1-l2, and with the help of alternative separable function algorithm to solve the model. As a result of the regularization method of norm l1-l2to the noise and ringing has a good inhibitory effect is that the recovery effect is very good. Introduction Image restoration is important in image processing. The specified degradation model can rejuvenate degraded images. Rotary motion blurred image is working in the high speed rotating platform. To some extent, there is considerable relative rotation angle between Imaging system in a short exposure time and the target, which results in a blurring of the acquired picture. Rotating motion blur is variable space, the farther from the image center of rotation, the lager fuzzy parameter is, and the higher the fuzzy degree is. The early researchers have provided many effective resolutions about the restoration of rotational motion blurred images. Sawchuk [1] puts forward a method for restoration based on geometric coordinate transformation. Hanyu Hong [2] presents the restoration of motion blur under the boundaries of non-zero values, and provide when fuzzy path beyond the pixel plane based on domain knowledge to guide the forehead secondary recovery algorithm. Shuyue Chen [3] puts forward the restoration of rotational motion blurred images based on difference method. First, the rotation of images should be change into linear motion blurring, and recover the image of transformation by difference method, then convert restoration image into the appropriate coordinate position. First, this paper introduces the model of rotating motion blur, the degradation function of rotating motion blur is derived, and from the angle of solving linear system of equations, common least-squares filtering algorithm is described, to show the advantage of regularization method on image restoration, then presents restoration algorithm based on regularization strategy, to solve the model with the help of alternative separable function algorithm. The model of rotational motion blurred images Generally, the model of motion blur is 0 0 0 ( , ) ( ( ), ( )) T g x y f x x t y y t dt = − − ∫ (1) T is exposure time, ) , ( y x f is the original image, ) , ( y x g is blurry image, ) ( ), ( 0 0 t y t x is fuzzy path. Though the pixel point is the line integral and superimposed along the fuzzy trajectory, in the process of the rotational motion blur, the fuzzy path is a series of concentric circles, and the model of rotational motion blurred images is 0 ( , ) ( cos( ), sin( )) T g x y f x r t y r t dt ω ω = − − ∫ (2) International Conference on Information Sciences, Machinery, Materials and Energy (ICISMME 2015) © 2015. The authors Published by Atlantis Press 945 We noted that ω is angular velocity, r is the distances from the rotation center to the pixel point. We write the equation in a form that corresponds with the polar geometry 0 1 ( , ) ( , ) T g l r f r l s ds T = − ∫ (3) Satisfying T r l ω = , t r s ω = By one-dimensional equation: 0 1 ( ) ( ) r a r r r g l f l s ds a = − ∫ (4) In order to carry on the type of discretization, we use Discrete coordinates i to present it: 1 ( ) [ ( ) ( 1) ( 1)] r r r r r r g i f i f i f i a a = + − + + − +  (5) We note that r a is blur extent, ) (x h is point spread function, we write it by the form of discrete convolution: 1 0 ( ) ( ) ( ) ( ) ( ) R N r r r r r m g i f m h i m f i h i − = = − = ∗ ∑ (6) Which is expressed in the matrix form, then get singular matrix

Health literacy plays a key role in a patient’s ability to use health information and services, and can affect health outcomes. This study aimed to explore radiation therapists’ perspectives on how they support people with lower health literacy who are undergoing radiotherapy. Semi-structured interviews were conducted with 25 radiation therapists working in radiation oncology departments in New South Wales, Australia. The four key themes were (1) the process of identifying a patient with low health literacy, (2) the perceived consequences of low health literacy, (3) managing and responding to the needs of different health literacy groups and (4) recommendations to address low health literacy in radiotherapy. Radiation therapists appeared to make an informal, intuitive judgment about a patient’s health literacy, using a variety of verbal and non-verbal cues as well as impromptu conversations with the multi-disciplinary team. Patients perceived to have lower health literacy were described as having greater difficulties assimilating knowledge and engaging in self-care. Although participants reported communicating to patients at a basic level initially, they subsequently tailored their communication to match a patient’s health literacy. Strategies reported to communicate to low health literacy groups ranged from using lay language with minimal medical terminology, using visual aids (photos), using analogies, reiterating information and asking family members with higher literacy to attend consultations. A more structured approach to supporting patients with low health literacy and integrating health literacy training in radiation oncology departments may help to minimise the adverse outcomes typically experienced by this population.