学会抄録

<p><b>Observation of pulmonary artery sections</b> (200X, HE) The pulmonary artery wall thickness of disease (D) is noticeably increased. In the D sample, 1) the tunica adventicia was more compact and exhibited increased connective tissue; 2) the smooth muscle fiber was thicker; 3) there was excessive fiber production; and 4) the intima was more compact. The arrows indicate the pathological changes.</p

Multiscale Investigation of Waste Soybean Oil Rejuvenated Asphalt Binder Utilising Experimental Methodologies and Molecular Dynamics Simulations

To Demonstrate the Rejuvenation Effect of Waste Soybean Oil (WSO) on Aged Asphalt Binder (AB) and Realise the Efficient Combination of Laboratory Evaluation and Numerical Simulation. the Rheological Properties and Molecular Dynamics Simulation of WSO Rejuvenated Binders Were Investigated. the Results Demonstrated that the WSO Provided Sufficient Light Components in the AB and Reduced the Stiffness. the WSO Rejuvenated Binders Were Transformed into a Sol–gel Structure, This Resulted in Excellent Rheological Properties. the WSO Improved the Anti-Fatigue Performance of Rejuvenated Binders. the WSO Provided Sufficient Aromatics and a Small Amount of Saturates for the AB. the Blending Mechanism of WSO and AB Was Physical Blending. the Atomic Force Microscopy Micromorphology Images Showed that the Bee-Like Structure of WSO Rejuvenated Binders Was Reduced in Quantity Compared with that of AB. the Dosages of 3–6 Wt% of AB Content Was Determined to Be the Optimum Content of WSO. the Molecular Dynamics Results Indicated that as the Amount of WSO Increased, the Total Volume and the Occupied Volume Increased, While the Free Volume Decreased. the Volume Fusion Parameters Increased Significantly with an Increase in the WSO Content. This Showed that WSO Effectively Improved the Diffusion Capacity of Rejuvenated Binders

Choroidal vascular changes in silicone oil-filled eyes after vitrectomy for rhegmatogenous retinal detachments

Abstract Introduction The tamponade of silicone oil (SO) can affect both the structure and blood flow of the retina. However, there are few studies on the effect of SO tamponade on choroidal blood flow. Our study aimed to compare the effects of SO tamponade on the choroidal vascular index (CVI) and choroidal thickness (CT) in patients with unilateral rhegmatogenous retinal detachment (RRD) with operated eyes and fellow healthy eyes. Methods We retrospectively collected demographic and clinical data from 36 patients who underwent 23G pars plana vitrectomy and SO tamponade for unilateral complicated RRD. Enhanced depth imaging-optical coherence tomography (EDI-OCT) scans were performed both within 1 week before SO removal and at the last follow-up visit after SO removal. Using ImageJ software, images were binarized to segment the total choroidal area, luminal area, and stromal area, respectively. The CVI was calculated as CVI=(luminal area)/(total choroidal area), and CT was also evaluated. Results During SO tamponade, the CVI and luminal area in operated eyes were significantly lower compared to fellow eyes (57.616 ± 0.030 vs. 60.042 ± 0.019, P < 0.0001; 0.909 [0.694; 1.185] vs. 1.091 [0.785; 1.296], P = 0.007). Even after SO removal, the CVI remained lower in operated eyes than in fellow eyes (59.530 ± 0.018 vs. 60.319 ± 0.020, P = 0.031). Both CVI and luminal area were lower in operated eyes before SO removal than after SO removal (57.616 ± 0.030 vs. 59.530 ± 0.018, P = 0.0003; 0.909 [0.694; 1.185] vs. 0.994 [0.712; 1.348], P = 0.028). The duration of SO tamponade was positively correlated with the difference in CVI between fellow eyes and operated eyes during SO tamponade (P = 0.035). Total choroidal area, stromal area, and CT did not differ significantly between fellow eyes and operated eyes or between pre- and post-SO removal. Conclusions SO tamponade reduces CVI and decreases choroidal blood circulation in patients with retinal detachments required vitrectomy combined with SO tamponade. The longer the SO tamponade time, the more CVI reduction. In future work, we will aim to reduce these side effects by shortening the duration of silicone oil filling

EP300 single nucleotide polymorphism rs20551 correlates with prolonged overall survival in diffuse large B cell lymphoma patients treated with R-CHOP

Abstract Background Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown. Methods In this study we analyzed the EP300 SNP rs20551 and prognosis of 226 DLBCL patients who treated with R-CHOP or R-CHOP-like regimes from 2002 to 2013. Determination of the EP300 SNP rs20551 from genomic DNA was obtained by Sanger chain termination sequencing. Result In this study, the frequency of the A and G allele of the EP300 SNP rs20551 in 226 patients were 92.5 and 7.5%, respectively. We did not observe obvious correlation between patients’ disease features and the EP300 SNP rs20551. But the patients with genotype AA had a higher 5-year overall survival rate than those with genotype GA (77.0% vs. 64.7%, p = 0.045). Furthermore, multivariate Cox regression analysis showed that the GA genotype of EP300 SNP rs20551 was an independent poor prognostic factor for DLBCL patients treated with Rituximab-chemotherapy (p = 0.009, HR 2.956, 95% CI 1.315–6.645). Conclusion This study suggests that EP300 SNP rs20551 might be a useful biomarker to predict the long-term outcome of R-CHOP in DLBCL patients

TP53 Arg72 as a favorable prognostic factor for Chinese diffuse large B-cell lymphoma patients treated with CHOP

Abstract Background TP53 Arg72Pro (SNP rs1042522) is associated with risk of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL. However, the relationship between this SNP and prognosis of DLBCL in Asians is unknown. Methods Genotyping of TP53 Arg72Pro was done in 425 Chinese DLBCL patients. Two hundred and eighty-nine patients were treated with R-CHOP, and 136 patients received CHOP or CHOP-like as frontline regimen. Three hundred and ninety-six patients were assessable for the efficacy. Results Patients with Arg/Arg and Arg/Pro at codon 72 of TP53 had a higher complete response rate (61% vs. 44%, P = 0.007) than those with Pro/Pro. In the subgroup treated with CHOP or CHOP-like therapy, patients with Arg/Arg and Arg/Pro showed a higher 5-year overall survival (OS) rate than those with Pro/Pro (68.8% vs. 23.2%, P = 0.001). Multivariate Cox regression analysis revealed TP53 Arg72 as a favorable prognostic factor in this group. However, the combination of rituximab with CHOP significantly increased the 5-year OS rate of patients with Pro/Pro to 63%. Conclusion This study revealed TP53 Arg72 as a favorable prognostic factor for Chinese DLBCL patients treated with CHOP or CHOP-like as frontline therapy

The prognostic landscape of interactive biological processes presents treatment responses in cancerResearch in context

Background: Differential gene expression patterns are commonly used as biomarkers to predict treatment responses among heterogeneous tumors. However, the link between response biomarkers and treatment-targeting biological processes remain poorly understood. Here, we develop a prognosis-guided approach to establish the determinants of treatment response. Methods: The prognoses of biological processes were evaluated by integrating the transcriptomes and clinical outcomes of ~26,000 cases across 39 malignancies. Gene-prognosis scores of 39 malignancies (GEO datasets) were used for examining the prognoses, and TCGA datasets were selected for validation. The Oncomine and GEO datasets were used to establish and validate transcriptional signatures for treatment responses. Findings: The prognostic landscape of biological processes was established across 39 malignancies. Notably, the prognoses of biological processes varied among cancer types, and transcriptional features underlying these prognostic patterns distinguished response to treatment targeting specific biological process. Applying this metric, we found that low tumor proliferation rates predicted favorable prognosis, whereas elevated cellular stress response signatures signified resistance to anti-proliferation treatment. Moreover, while high immune activities were associated with favorable prognosis, enhanced lipid metabolism signatures distinguished immunotherapy resistant patients. Interpretation: These findings between prognosis and treatment response provide further insights into patient stratification for precision treatments, providing opportunities for further experimental and clinical validations. Fund: National Natural Science Foundation, Innovative Research Team in University of Ministry of Education of China, National Key Research and Development Program, Natural Science Foundation of Guangdong, Science and Technology Planning Project of Guangzhou, MRC, CRUK, Breast Cancer Now, Imperial ECMC, NIHR Imperial BRC and NIH. Keywords: Prognosis, Biological processes, Treatment response, Cell-proliferation, Immune processe

ITK inhibition induced in vitro and in vivo anti-tumor activity through downregulating TCR signaling pathway in malignant T cell lymphoma

Abstract Background Angioimmunoblastic T cell lymphoma (AITL) is a distinct subtype of peripheral T cell lymphoma and associated with poor outcomes. The activation status of T cell receptor (TCR) signaling has recently become a focus of attention in terms of the therapeutic targets. However, the molecular pathogenesis mechanisms and novel therapeutic targets are largely unknown. Methods Antibodies specific to phosphorylated ZAP70, ITK and PLCγ1 were used to identify the activation status of intracellular proteins involved in TCR signaling in AITL patients. Malignant T cell lymphoma cells were transduced with a lentiviral construct containing ITK shRNA for cellular and functional assays. The antitumor effects of the selective ITK inhibitor BMS-509744 were determined in vitro and in vivo. Results Immunohistochemistry staining showed that more than half of the AITL patients (n = 38) exhibited continuously activated intracellular TCR signaling pathway. Patients positive for phosphorylated ITK showed a lower rate of complete response (20% vs. 75%, P = 0.004) and a shorter progression-free survival (5.17 months vs. 25.1 months, P = 0.022) than patients negative for phosphorylated ITK. Genetic and pharmacological cellular ITK inhibition significantly compromised the proliferation, invasion and migration of malignant T cells. The selective ITK inhibitor BMS-509744 also induced the pro-apoptotic effects and G2/M phase cell cycle arrest in vitro and in vivo. Finally, inhibition of ITK synergistically enhanced the antitumor effect of vincristine and doxorubicin on malignant T cell lymphoma cell lines. Conclusions Our findings suggest that ITK may be a novel candidate therapeutic target for the treatment of patients with ITK-expressing malignant T-cell lymphomas

qRT-PCR and sequencing.

<p>qRT-PCR validation of differentially expressed genes in disease and normal samples of pulmonary artery for 12 genes.</p

Basic summary of sequence and sequencing reads mapping to reference genome.

<p>Basic summary of sequence and sequencing reads mapping to reference genome.</p