Search

The thrombodynamic ratio (TDR) as a composite thromboelastography (TEG) parameter, has been proven to be valuable in multiple diseases. However, the association between TDR and mortality in sepsis has not been studied.One hundred forty-one patients were enrolled in this retrospectively study. TEG was performed immediately at admission. Two cox proportional hazards models were developed for the prediction of 28-day mortality. The C statistic, continuous net reclassification index (cNRI) and integrated discriminatory index (IDI) were calculated to compare the discrimination performance of clinical models with and without the TDR value. The integrated calibration index (ICI) and E50 were calculated to compare the calibration.Patients with lower TDR were more likely to have organ impairments and increased 28-day mortality. The TDR value improved discrimination performance in both Model 1 (C statistic, 0.745 vs 0.735; cNRI 19.4%, p = 0.044; IDI 5.6%, p = 0.012) and Model 2 (C statistic, 0.761 vs 0.751; IDI, 5.1%, p = 0.012). Compared to the calibration curve of Model 1 without TDR, addition of TDR displayed better calibration (ICI, 0.023; E50, 0.021).TDR value significantly predicts 28-day mortality in patients with sepsis and could improve the discrimination and calibration performance of clinical prediction models.

We developed a new core-shell ratiometric fluorescent nanoprobe simply prepared by a seeded growth method. The strong luminescence arising from the shell formed by coordination self-assembly of an alkaline phosphatase (ALP) substrate, l-ascorbic acid 2-phosphate (AAP), and Tb

Recent studies have shown that Ankyrin Repeat Domain 55 (For this study, we enrolled 2050 subjects, consisting of 1220 patients with AITD and 830 healthy subjects. Five loci (rs321776, rs191205, rs7731626, rs415407, and rs159572) of theThe results showed that the allele frequencies of rs7731626 and rs159572 loci in HT patients were lower than those in normal controls (This study for the first time found that rs7731626 and rs159572 of

The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.

As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathogenesis of GD. Here, we for the first time reported the DNA methylation pattern in GD through a high-throughput analysis. In order to investigate genome-wide DNA methylation profile of GD, methyl-DNA immunoprecipitation (MeDIP) and Nimblegen human DNA methylation 3 × 720 K promoter plus CpG island microarrays were used to identify differentially methylated regions (DMRs) from blood samples in GD patients. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation state of candidate genes. Transcription level of each gene was estimated by quantitative real-time PCR (qRT-PCR). A total of 132 hypermethylated and 133 hypomethylated regions were identified in GD. The methylation of ICAM1 in GD patients and normal controls was significantly different (p

Background and Aims: Abnormal microRNA (miRNA) expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD). Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. Methods: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls) were also collected for further validation by quantitative real-time PCR ( qRT-PCR ). Results: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC≥1.3 or≤0.77 and p

Objective: The aim of this study was to investigate UBASH3A gene variation association with autoimmune thyroid disease and clinical features in a Chinese Han population. Subjects and methods: A total of 667 AITD patients (417 GD and 250 HT) and 301 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) rs11203203, rs3788013 of UBASH3A gene, utilizing the Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform. Results: Between the control group and AITD, GD and HT group, no statistically significant difference was observed in the genotypic and allelic frequencies of the two SNPs. There was no significant difference in allelic frequencies of the two SNPs between GD with and without ophthalmopathy. There was no significant difference in haplotype distributions between the control group and AITD, GD or HT group. Conclusion: Rs11203203 and rs3788013 in UBASH3A gene may not be associated with AITD patients in Chinese Han population.

To investigate the association of CLEC16A gene polymorphisms and autoimmune thyroid diseases (AITDs). Six hundred sixty seven Han Chinese patients with AITDs were selected as study subjects, including 417 patients with Graves’ disease (GD), 250 patients with Hashimoto’s thyroiditis (HT) and 301 healthy control patients. Polymerase chain reaction-restriction fragment length polymorphism (RFLP) and the mass spectrometry technique were used to genotype five CLEC16A single-nucleotide polymorphisms (SNPs) (rs12708716, rs12917716, rs12931878, rs2903692, and rs6498169). Higher frequency of G allele of rs6498169 CLEC16A gene in AITDs patients [P = 0.029, odds ratio (OR) 1.29 and 95% confidence interval 1.022−1.505] was observed. In addition an association between rs6498169 and HT was observed with statistical significance (P = 0.018, OR 1.335, 95% confidence interval 1.051−1.696). Furthermore, the GG haplotype containing the major allele of (rs12708716 and rs6498169) was associated with an increased risk of HT (P = 0.0148, OR 1.344). When patients with HT and controls were compared, results from the dominant and recessive models showed that the genotype frequency of rs6498169 were at borderline levels (P = 0.054 and P = 0.05), and the other four SNPs of CLEC16A gene showed no significant association with AITDs. Our results suggest that polymorphisms rs6498169 of CLEC16A gene confers susceptibility to AITDs. We therefore disclose for the first time the association of rs6498169 SNP with AITDs.

The aim of this study was to investigate the association between signal transducer and activator of transcription 3 (STAT3) polymorphisms and autoimmune thyroid diseases and clinical features. We genotyped six single-nucleotide polymorphisms (SNPs) rs1053005, rs2293152, rs744166, rs17593222, rs2291281, and rs2291282 of STAT3 gene in 667 patients with autoimmune thyroid disease (417 Graves' disease (GD) and 250 Hashimoto's thyroiditis (HT)) and 301 healthy controls. The allele A from rs1053005 was significantly less frequent in both GD and HT patients (P = 0.0024, OR = 0.6958, 95%CI = 0.5508-0.8788; P = 0.0091, OR = 0.7013, 95%CI = 0.5397-0.9112, respectively). The AA genotype of rs1053005 was less in GD and HT patients too (P = 0.0025,OR = 0.6278, 95%CI = 0.466-0.847) and (P = 0.0036,OR = 0.601, 95%CI = 0.428-0.843). The allele G from rs17593222 increased the susceptibility to the ophthalmopathy development both in autoimmune thyroid disease (AITD) and GD patients (P = 0.0007, OR = 3.980, 95%CI = 1.871-8.464; P = 0.0081, OR = 3.378, 95%CI = 1.441-7.919, respectively). The allele A and AA genotype of SNP rs1053005 may protect individuals from the susceptibility to AITD and their frequency decreased in AITD patients. In addition, the allele G of rs17593222 may increase the ophthalmopathy risk in AITD patients. Our findings suggest the existence of association between STAT3 gene and AITD, thus adding STAT3 gene to the list of the predisposing genes to AITD.

There is an increasing focus on the effective methods to develop low-permeability reservoirs, especially for ultra-low permeability reservoirs. It is hard to achieve the expected stimulation effect only on the traditional single fracturing, because of the poor supply ability from the matrix to fracture in low-permeability reservoirs. Volume stimulating to reservoir, achieving short distance from matrix to fracture because of producing fracture network. So the volume fracturing technology proposed for increasing oil or gas production, this technology is suitable for low porosity and low permeability reservoir. The conventional simulation method can't describe the complex fracture network accurately,but this paper established hydraulic fracturing complex fracture model based on the finite element numerical simulation method , making the simulated complex fracture more close to the real description,it can accurately describe the flow state in the reservoir and cracks.It has an important reference value to the low permeability reservoirs.

On the basis of the study of sediment types and dynamic partition zones of heavy minerals assemblage, silt transport tendency in Beidai River coastal sediment are discussed. According to the outcome of analysis of 47 samples of the heavy minerals in Beidai River coastal sediment, it is shown that: (1) there are three heavy minerals epidote, amphibole and iron that were rich in mineral content; (2) light and heavy mineral separation was better, the distribution of which showed a clear saddle shape, and two kinds of high minerals and low showed a pattern of alternate distribution; (3) the general trend of silt transport in Nandai River estuary mouth to the ocean is from southwest to northeast, but on the root of the land to the sea in Beidai River District, the direction of silt transport is from the root to the two wings extending.his template explains and demonstrates how to prepare your camera-ready paper for Trans Tech Publications. The best is to read these instructions and follow the outline of this text.

In this paper, the single and double eccentric combination of pressure regulation device in the offset press was as the object. A closed loop control system of printing pressure and a following pressure regulation device were designed. The rotation angle of eccentric bearing in plate cylinder and the length change of regulating screw were worked out by means of the vector relationship of pressure regulation. The influence on printing quality from the pressure regulation device was analyzed, and it provided a certain basis for the regulation and control of printing pressure.

Background Single nucleotide polymorphisms (SNPs) of the miR-146a, miR-499a and miR-125a have been shown to be associated with the susceptibility to several autoimmune diseases. This study was conducted to identify the association of SNPs rs2910164, rs57095329, rs3746444 and rs12976445 with autoimmune thyroid diseases (AITDs) in a Chinese Han population. Methods We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Four SNPs were selected for genotyping by multiplex polymerase chain reaction and ligase detection reaction. Results The frequencies of rs3746444 genotypes in patients with AITD and GD differed significantly from those in the controls. The frequencies of rs12976445 genotypes in patients with HT differed significantly from those in the controls. The frequencies of allele C in HT groups were significantly higher than those in control group. For the rs3746444 polymorphism, genetic associations between the combinational genotype and AITD/GD risk were observed in the dominant model, recessive model, and overdominant model. For the rs12976445 polymorphism, genetic associations between the combinational genotype and HT risk were also found in the dominant model and overdominant model. Moreover, gene-sex interactions were identified by GMDR and 2 × 2 crossover analysis. Conclusions Our results suggest rs3746444 (miR-499a) and rs12976445 (miR-125a) associated with AITD susceptibility and potential gene-sex interactions between the four polymorphisms and AITD.

The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.

In order to analyze the influence on the motion state of on-off pressure mechanism with flexible link of offset press, pneumatic on-off pressure was as the research object, the three-dimensional model of on-off pressure mechanism was established by using ADAMS, the kinematics simulations of the on-off pressure process was carried out, the curve of the angular velocity, angle acceleration and displacement between rollers of eccentric bushing in both rigid and the rigid-flexible coupled system was got, the significant basis of optimal design for on-off pressure mechanism was provided.

In order to analyze the influence on the printing graphics from the deformation of the printing cylinders and blankets, in this paper, offset printing unit was as the research object, the three-dimensional assembly model of printing cylinders was established by using SolidWorks , the model was imported into finite element software ANSYS, by using ANSYS nonlinear contact calculated functionality, the face-to-face contact of impression surface between plate cylinder and blanket cylinder, blanket cylinder and impression cylinder were established, the stress and strain distribution of blanket were obtained, and the elongation value of circumferential and radial direction of blanket were got, the dot enlargement value was received by simulation analysis.

The cross sections for the elastic scattering of protons from tritium at 151° and from helium at 155° angles in the laboratory frame, over the energy range of 1.2–3.4 MeV, have been measured in the present work, as a supplement to previous cross section measurements determined at different scattering angles recently. The currently measured cross section data are compared to data available in literature. The cross section enhancement was also investigated for both reactions. It was found that over the whole measured energy range, the elastic cross section for protons on tritium increases linearly with energy and is about 1000 times greater than the Rutherford cross section at 3.4 MeV. On the other hand, in the case of the elastic scattering of protons from helium, the cross section below 2.3 MeV increases almost linearly, and reaches a maximum of about 300 mb/str at the energy of 2.4 MeV for the scattering angle of 165°, and then, after this energy, it keeps oscillating around the maximum.

Si-Ni-San, a traditional Chinese medicinal formula, exerts an important function in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice, but the underlying mechanism is still unclear. In this study, we investigated the therapeutic potential of Si-Ni-San and its ingredient glycyrrhizin in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice, a well-characterized murine model for Crohn's disease. Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis with reduced mortality and recovery of body weights. In addition, Si-Ni-San and glycyrrhizin dose-dependently decreased macroscopic inflammation scores, microscopic histological scores, and myeloperoxidase activity. Furthermore, Si-Ni-San and glycyrrhizin caused a decrease in pro-inflammatory cytokines including IFN-gamma, IL-12, TNF-alpha and IL-17 and an increase in regulatory cytokine IL-10 in colon of the mice. It should be noticed the therapeutic effect of Si-Ni-San at 450 mg/kg was much better than that of its contained content of glycyrrhizin at 10 mg/kg. In conclusion, Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis in mice through regulating pro- and anti-inflammatory cytokine production.

In the present study, we aimed at examining the immunosuppressive activity of saikosaponin a, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), and the underlying mechanisms. Saikosaponin a significantly inhibited the proliferation and activation of T cells activated by concanavalin A (Con A) in a concentration-dependent manner. Additionally, it potently suppressed Con A-stimulated IL-2, IFN-gamma and TNF-alpha production in mouse T cells. Saikosaponin a also caused G0/G1 arrest of activated T cells through down-regulating the protein levels of CDK6 and Cyclin D3 and up-regulating the protein level of p27(kip). Furthermore, the compound dose-dependently induced apoptosis of Con A-activated T cells rather than those non-activated, as determined by Annexin V/PI staining. Besides, it induced a remarkable collapse of mitochondrial membrane potential and caused significant release of cytochrome c from mitochondria to cytosol. In summary, these results suggest that the G0/G1 arrest as well as the induction of apoptosis via mitochondrial pathway are involved in the immunosuppressive activity of saikosaponin a against activated T cells. This may herald a novel approach for further studies of saikosaponin a as a candidate for the treatment of inflammatory and autoimmune diseases.

The objective of this study was to investigate histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with Graves' disease (GD). Thirty GD patients and 20 healthy controls were enrolled in this study. Global histone H3/H4 acetylation levels of PBMCs in all subjects were detected by enzyme-linked immunosorbent assay. mRNA levels of histone-related chromatin modifier genes were measured by real-time quantitative reverse transcription-polymerase chain reaction. Global histone H4 acetylation level in PBMCs of GD patients was significantly decreased compared with controls (p=0.005). The mRNA expression of histone deacetylases HDAC1 and HDAC2 were significantly increased in PBMCs of GD patients compared with controls (p=0.004 and 0.018; respectively). No significant difference was observed either in SIRT1 or in HATs mRNA including p300, CREBBP between GD patients and controls (p>0.05). Our findings firstly suggested that histone acetylation modifications are aberrant in PBMCs of GD patients, possibly due to the deregulation of epigenetic modifier genes.

A series of novel chrysin derivatives was firstly synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents. Among them, compounds 5c displayed the most potent immunosuppressive inhibitory activity with IC 50 of 0.78 μM, which was comparable to that of cyclosporin A (IC 50 = 0.06 μM). The preliminary mechanism of compound 5c inhibition effects was also detected by flow cytometry (FCM), and the compound exerted immunosuppressive activity via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Furthermore, the estimated LD 50 (in mg/kg) in vivo of compound 5c is 738.2, which indicated that compound 5c was low toxic.

Regulation of signal transducer and activator of transcription (STAT) 1 signaling is being explored as a new approach to the treatment of inflammatory bowel diseases. However, few chemicals have been reported to inhibit IFN-gamma/STAT1 signaling for Crohn's disease therapy. In the present study, we found that cirsilineol, a small natural compound isolated from Artemisia vestita, significantly ameliorated trinitro-benzene sulfonic acid (TNBS)-induced T-cell-mediated experimental colitis in mice, which was closely associated with reduced autoreactive T-cell proliferation and activation. Moreover, the regulatory action of pro-inflammatory and anti-inflammatory cytokine by cirsilineol treatment was found to decrease the activity of effector Th1 cells but increase the activity of regulatory T cells as characterized by down-regulation of IFN-gamma and corresponding up-regulation of IL-10 and TGF-beta. The therapeutic effect of cirsilineol was attributable to a novel regulatory mechanism with selective inhibiting IFN-gamma signaling in colonic lamina propria CD4(+) T cells, which was mediated through down-regulating STAT1 activation and T-bet expression. Furthermore, cirsilineol was found to down-regulate the activation of JAK2, a critical kinase for IFN-gamma/STAT1 signaling, and abrogate the expression of T-bet, resulting in markedly decreased proliferation and activation of T cells in vitro. Importantly, the inhibition of IFN-gamma/STAT1 signaling by cirsilineol was reversible in the presence of high level of IFN-gamma. These results strongly suggest that cirsilineol might be potentially useful for treating T-cell-mediated human inflammatory bowel diseases.

Aims The roles of specific active ingredients in Chinese medicinal formulas have not been clearly elucidated. In this study, we selectively deleted and replenished paeoniflorin from Si-Ni-San, a traditional Chinese prescription, and aimed to identify the molecular basis of how paeoniflorin exerted its effect in Si-Ni-San. Main methods Contact dermatitis was induced in mice with picryl chloride. Paeoniflorin was selectively deleted from Si-Ni-San by an immunoaffinity column. Quantitative real-time PCR, western blot, and enzyme-linked immunosorbent assay were used in this study. Key findings Both Si-Ni-San and paeoniflorin significantly reduced ear swelling in mice while the paeoniflorin-deleted Si-Ni-San (Si-Ni-San PF− ) showed little ameliorative effect. In lipopolysaccharide-evoked macrophages, Si-Ni-San and paeoniflorin markedly inhibited tumor necrosis factor-α production, cyclooxygenase-2 activity, as well as extracellular signal-regulated kinase 1/2 phosphorylation while Si-Ni-San PF− exhibited no or slight inhibitory effect. Furthermore, the inhibitory effect on the production of tumor necrosis factor-α reappeared when different proportions of paeoniflorin were replenished in Si-Ni-San PF− . In addition, the expression of macrophage migration inhibitory factor in T cells, rather than macrophages, was significantly inhibited by Si-Ni-San, but not Si-Ni-San PF− . Our data indicate paeoniflorin is the principal component of Si-Ni-San, exerting negative regulation on the function of macrophages in contact dermatitis. Significance The present study suggests that dissecting the role of specific constituents in medicinal formulas through selective deletion and replenishment may be a useful strategy in recognizing and validating an active ingredient in traditional Chinese medicine.