Purpose:Our previous study has demonstrated that high expression of immune checkpoints (ICs) was significantly associated with adverse clinical outcomes in patients with acute myeloid leukemia (AML). This study aims to investigate the significance of the alteration of IC co-expression for evaluating the prognosis of AML patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods:Quantitative real-time PCR (qRT-PCR) data of bone marrow (BM) samples from 62 de novo AML patients, including 37 patients who received allo-HSCT and 25 patients who received chemotherapy only, were used for prognostic analysis. Results:High expression of PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 was associated with poor overall survival (OS) in AML patients receiving allo-HSCT, while the expression levels of PD-1, PD-L2, CTLA-4, and LAG-3, other than PD-L1, were not significantly correlated with OS in AML patients receiving chemotherapy. Importantly, PD-L1/CTLA-4 was the best combination model for predicting poor OS in AML patients following allo-HSCT, especially combined with minimal residual disease (MRD). Conclusion:High expression of ICs in BM of AML patients following allo-HSCT was related to poor outcomes, and increasing co-expression of PD-L1 and CTLA-4 might be one of the best immune biomarkers to predict outcomes in patients with AML.

Cellular immune disorder is a common characteristic of myelodysplastic syndrome (MDS). Abnormal natural killer (NK) cell function has been reported in MDS patients, and this is closely related to disease progression and poor prognosis. However, little is known about the association between the abnormal immune checkpoint (IC) that results in abnormal immune NK cell function and the prognosis of MDS. In this study, RNA-sequencing data from 80 patients in the GSE114922 dataset and bone marrow (BM) samples from 46 patients with MDS in our clinical center were used for overall survival (OS) analysis and validation. We found that the NK cell-related IC genes PDCD1, TIGIT, CD47, and KIR3DL2 had higher expression and correlated with poor OS for MDS patients. High expression of PDCD1 or TIGIT was significantly associated with poor OS for MDS patients younger than 60 years of age. Moreover, co-expression of PDCD1 and TIGIT had the greatest contribution to OS prediction. Interestingly, PDCD1, TIGIT, CD47, and KIR3DL2 and risk stratification based on the Revised International Prognostic Scoring System were used to construct a nomogram model, which could visually predict the 1-, 2-, and 3-year survival rates of MDS patients. In summary, high expression of IC receptors in the BM of MDS patients was associated with poor OS. The co-expression patterns of PDCD1, TIGIT, CD47, and KIR3DL2 might provide novel insights into designing combined targeted therapies for MDS.

•The deep learning architecture fused with the model-driven probability bubble approach is proposed to segment OD in abnormal fundus images to improve the performance when lack sufficient training samples in medical community.•A brand-new unsupervised probability bubble technique is figured out according to the position relationship between retinal vessels an OD, by which the main blood vessels are fitted by line segments through hough transform, and the density of intersection points of the lines indicates the probability of OD.•The joint probability of data-driven U-net and model-driven probability bubble approach is calculated to locate the OD. The localization based on the joint probability is more robust than each independent method, which ensures effectiveness of the proposed method.•The work in this paper provides a reference for the application of deep learning in medical community that the model-driven approach can be fused into the architecture and promote the performance when there are insufficient training samples available and deep learning can’t provide an accurate result.

Background RNA binding proteins (RBPs) have previously been demonstrated to be involved in the initiation and development of human cancers. However, its role in clear cell renal cell carcinoma (ccRCC) is not yet clear. The study was intended to explore the diagnostic and prognostic value of RBPs in ccRCC via bioinformatics methods of public datasets. Methods Data download from the Cancer Genome Atlas (TCGA) database was used to identify differentially expressed RBPs between normal renal samples and cancerous samples. Then, we performed the gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of differentially expressed genes (DEGs) using the ClusterProfiler package. Next, the protein-protein interaction (PPI) network was built by the online tool STRING database and Cytoscape software. The significant module and hub genes were screened by MCODE and Cytohubba plugin, respectively. Lastly, we performed a systematical analysis to investigate the diagnostic and prognostic value of candidate RBPs. Results A total of 133 DEGs, including 39 upregulated RBPs and 94 downregulated RBPs, were screened between ccRCC samples and noncancerous samples. From these data, eight candidate RBPs (RPS2, GAPDH, RPS20, EIF4A1, RPL18, RPL13, RPL18A, and RPS19) were identified. Conclusions In summary, we screened differentially expressed RBPs of ccRCC, which were enriched mainly in various biological processes and signaling pathways. Furthermore, we identified eight candidate RBPs, which could serve as potential biomarkers of ccRCC.

Saliency integration has attracted much attention on unifying saliency maps from multiple saliency models. Previous offline integration methods usually face two challenges: 1) if most of the candidate saliency models misjudge the saliency on an image, the integration result will lean heavily on those inferior candidate models; and 2) an unawareness of the ground truth saliency labels brings difficulty in estimating the expertise of each candidate model. To address these problems, in this paper, we propose an arbitrator model (AM) for saliency integration. First, we incorporate the consensus of multiple saliency models and the external knowledge into a reference map to effectively rectify the misleading by candidate models. Second, our quest for ways of estimating the expertise of the saliency models without ground truth labels gives rise to two distinct online model-expertise estimation methods. Finally, we derive a Bayesian integration framework to reconcile the saliency models of varying expertise and the reference map. To extensively evaluate the proposed AM model, we test 27 state-of-the-art saliency models, covering both traditional and deep learning ones, on various combinations over four datasets. The evaluation results show that the AM model improves the performance substantially compared to the existing state-of-the-art integration methods, regardless of the chosen candidate saliency models.

Abstract In our country, hydraulic concrete structure construction technology is widely used. However, with the increase of time and the erosion of the environment, there will be aging and safety risks in this structure. This puts forward higher requirements for detection technology and safety assessment technology of hydraulic concrete structures. Therefore, in order to promote the innovation and progress of this engineering technology, we should carry out targeted strategy analysis based on the development and application status of related technologies and engineering practice. We should also actively introduce advanced detection technology and equipment to maintain the development of China’s hydraulic concrete structure construction technology. This is conducive to the vigorous and healthy development of China’s water conservancy projects.

The papers in this special section examine compact and efficient feature representation and learning in computer vision.

Accurate segmentation of Optic disc (OD) is significant for the automation of retinal analysis and retinal diseases screening. This paper proposes a novel optic disc segmentation method based on the saliency. It includes two stages: optic disc location and saliency-based segmentation. In the location stage, the OD is detected using a matched template and the density of the vessels. In the segmentation stage, we treat the OD as the salient object and formulate it as a saliency detection problem. To measure the saliency of a region, the boundary prior and the connectivity prior are exploited. Geodesic distance to the window boundary is computed to measure the cost the region spends to reach the window boundary. After a threshold and ellipse fitting, we obtain the OD. Experimental results on two public databases for OD segmentation show that the proposed method achieves the state-of-the-art performance.

Objective To investigate the association between the T cell inhibitory receptor programmed death 1 (PD-1) and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia (AML) and AML in complete remission (CR). Methods Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+, CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed, untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry. Twenty-three healthy individuals served as control. Results A significantly higher percentage of PD-1+ cells were found for CD3+ T cells in the de novo AML group compared with healthy controls. In addition, an increased level of PD-1+CD8+ T cells, but not PD-1+CD4+, was found for CD3+ T cells in the de novo AML and AML-CR samples. A higher percentage of CD244+CD4+, CD244+CD8+, CD57+CD4+ and CD57+CD8+ T cells was found in CD3+ T cells in samples from those with de novo AML compared with those from healthy controls. Strong increased PD-1+CD244+ and PD-1+CD57+ co-expression was found for CD4+ and CD8+ T cells in the de novo AML group compared with healthy controls. Conclusions We characterized the major T cell defects, including co-expression of PD-1 and CD244, CD57-exhausted T cells in patients with de novo AML, and found a particular influence on CD8+ T cells, suggesting a poor anti-leukemia immune response in these patients.

Atherosclerosis is the major cause of stroke and heart disease. However, the course and pathogenesis of atherosclerosis remains unknown. The proliferation and migration of endothelial cell play important roles in the inition and pathological progression of atherosclerosis. In this study, we demonstrated that long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) expression level was higher in coronary artery disease (CAD) tissues than in normal arterial tissues. The expression level of HOTTIP was upregulated in the proliferating endothelial cells induced by TNF-α or PDGF-BB. Ectopic expression of HOTTIP promoted endothelial cell proliferation and also increased the expression of proliferating makers cyclin D1 and PCNA. Moreover, elevated expression of HOTTIP promoted endothelial cell migration. Downregulation expression of HOTTIP suppressed endothelial cell proliferation and migration. Furthermore, we determined that overexpression of HOTTIP induced β-catenin expression and enhanced the downstream protein c-Myc expression in the endothelial cell. Ectopic expression of HOTTIP increased endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway. These results suggested that HOTTIP might manipulate the endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway.

T cell immunodeficiency is the common characteristics in patients with AML, which may play an important role in leukemia progression and promote the expansion of malignant clones. Recently, increasing data showed that the immunosuppressive microenvironment, such as overexpression of the T cell immunosuppressive receptors, including programmed death-1 (PD-1) or cytotoxic T lymphocyte antigen-4 (CTLA-4), Tim-3 and BTLA may be related to tumor immunosuppression and poor prognosis. Our previous studies indicated that the T cell immunodeficiency in leukemia patients are characterized by peripheral T cells that are incapable of interacting with blasts, reduced the thymic output function, oligoclonally restricted T cell repertoires, and led to low activation and a low antigen response. However, little is known the alterative expression of T cell immunosuppressive receptors in T cells, as well as their role in T cell exhaustion and immunosupression in AML patients.

The clonally expanded T cells identified in cancer patients that specific respond to tumor-associated antigen (TAA) have definite. We previously identified a high frequency of oligoclonal expansion of the Vβ21 T cell subfamily in the peripheral blood (PB) from BCR-ABL positive chronic myeloid leukemia (CML) and B cell acute lymphocytic leukemia (B-ALL) patients, and the TCR Vα13/Vβ21 gene modified T cell maintained anti-CML cytotoxicity. However, little is known whether there are any TCR Vβ specific for the mutant BCR-ABL protein. In this study, we analyzed the TCR β repertoire in PB from two cases with CML in blastic crisis (CML-BC) with ABL gene mutation, case 1 with B-cell resembling lymphoid blast crisis (LBC) contained single kinase domain mutation (T315I), and case 2 with AML resembling myeloid blast crisis (MBC) contained compound-mutant BCR-ABL1 (L387M and T315I). Using RT-PCR and genescan analysis, clonally expanded Vβ17 was identified in samples from both cases. The size of clonal peak in PCR products which indicate the Vβ17 CDR3 length, was all in 181 bp, this indicated that both samples contained Vβ17 clones with similar CDR3 rearrangement. Interesting, the same size clonally expanded Vβ17 T cells was also identified in case 2 at 51 days after HLA-matched sibling hematopoietic stem cell transplantation (HSCT), which is thought from donor origin rather than recipient origin. This result indicated the possibility that the expanded Vβ17 clones may respond to CML associated antigen, particularly for mutant T315I-ABL. Moreover, clonally expanded Vβ18 T cells was identified in case 1, while clonally expanded Vβ15 T cells was found in case 2, this is thought to be individual response to CML associated antigen. In conclusion, our findings showed a identical clonal TCR Vβ17 expansion in CML-BC cases with T315I-ABL mutation. Further investigation will be performed to characterize the function of Vβ17+T cell clone in T315I-ABL mutant CML-BC patients. This study was supported by grants from the NSFC (81270604 and 81400109)

Osteoarthritis (OA) causes progressive degeneration of articular cartilage and pathological changes in subchondral bone. These changes can be assessed volumetrically using micro-computed tomography ( μ CT) imaging. The local descriptor, i.e. local binary pattern (LBP), is a new alternative solution to perform analysis of local bone structures from μ CT scans. In this study, different trabecular bone samples were prepared from patients diagnosed with OA and treated with total knee arthroplasty. The LBP descriptor was applied to correlate the distribution of local patterns with the severity of the disease. The results obtained suggest the appearance and disappearance of specific oriented patterns with OA, as an adaptation of the bone to the decrease of cartilage thickness. The experimental results suggest that the LBP descriptor can be used to assess the changes in the trabecular bone due to OA.

Abstract Abstract Tumor specific or related antigen cytotoxic lymphocyte (CTL) have been identified in chronic myeloid leukemia patients, however, whether they are constituted by specific type of T cell receptor chains has not been illustrated so far. Previous studies have reported abnormal TCR repertoires and clonally expanded TCR Vβ T cells in chronic myeloid leukemia in chronic phase (CP-CML). In this study, we investigated the distribution and clonality of the TCR Vβ repertoire in 5 CML patients in blast crisis (BC-CML) and one in acceleration phase (AP-CML) with ABL kinase domain mutations (KDMs) including T315I, E255K, F317L+S417Y, Y-253F and L387M+T-315A. Examination of TCR Vβ expression and clonality was performed by reverse transcription-polymerase chain reaction (RT-PCR) combined with GeneScan analysis. Significantly skewed TCR Vβ repertoires were observed in those patients, and 4 to 8 oligoclonally expanded TCR Vβ subfamilies could be identified in each sample, which distributed in 15/24 different subfamilies (TCR Vβ4, Vβ5, Vβ6, β8, Vβ9, Vβ10, Vβ15, Vβ16, Vβ17, Vβ18, Vβ19, Vβ21, Vβ22, Vβ23, Vβ24). Intriguingly, a relatively highly expanded Vβ9 clone with the same length as CDR3 (139 bp) was found in all three CML patients in lymphoid blast crisis (LBC-CML) who had different KDMs, but the clone was not detected in the other two CML patient in myeloid blast crisis (MBC-CML) or the one CML patients in accelerated phase. In conclusion, restricted TCR Vβ repertoire expression and decreased clone complexity was a general phenomenon in the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency status of these patients, and clonally expanded Vβ9 T cell clones may represent a specific immune response to leukemia-associated antigens in LBC-CML patients. Disclosures Li: The Foundation for High-level Talents in Higher Education of Guangdong, China ([2013]246-54),and the Guangzhou Science and Technology Project Foundation (201510010211): Research Funding; National Natural Science Foundation of China (81270604, U1301226, and 81400109), the Guangdong Natural Science Foundation (S2013040016151 and S2013020012863): Research Funding.

Objective To explore the efficacy of tacrolimus in treating experimental autoimmune prostatitis (EAP) in rat model and the possible mechanism.Methods SD rats were randomly divided into 4 groups:normal control group,EAP model group,low-dose treatment group,high-dose treatment group.According to administration durations,each group was further divided into two subgroups:2-week group and 4-week group.After successful modeling,rats in low-dose treatment group and high-dose group underwent gastric perfusion with 0.2 mg/(kg·day) and 0.8 mg/(kg·day) tacrolimus respectively for 2 and 4 weeks in a successive way.Concentrations of interleukin (IL)-2 and macrophage inflammatory protein-1α (MIP-1α) in the homogenate of prostatic tissue and serum were tested.Histomorphological changes of prostatic tissue,spleen and thymus gland were observed,with their viscera coefficients being calculated.Results After the intervention of tacrolimus,a decrease in inflammatory cells in prostatic tissue was revealed histomorphologically and glandular cavity wall was repaired to some extent.The concentrations of IL2 were ( 156.80 ± 19.11 ),( 124.56 ± 17.20) and ( 114.46 ± 20.65) ng/L in the serum of M2W,L2W and H2W groups,and MIP-1 α concentrations were ( 164.99 ± 22.25 ),( 112.03 ± 19.90) and ( 104.91 ± 11.91 ) ng/L,respectively.As for the homogenate of prostatic tissue,IL-2 and MIP-1α levels stood at (219.26±23.11),(191.56±19.08),(186.63 ±20.90) ng/L,and (216.46 ±18.50),(196.55 ±17.84),( 194.74 ± 18.14) ng/L respectively.In comparison,in M4W,LAW and H4W groups,concentrations of the two substances were ( 156.23 ± 19.83),( 129.27 ± 17.25),( 134.26 ± 16.11 ) ng/L and (157.93 ±34.55),(159.09 ±29.17),(154.54 ±29.85) ng/L,respectively.In the homogenate of prostatic tissue,data were (217.92 ±23.23),(186.07 ± 11.56),(180.37 ± 18.26) ng/L and (209.66 ±14.65),( 186.17 ± 17.79),( 186.16 ± 18.27) ng/L,respectively.All differences were statistically significant except MIP-1α level in the serum of 4-week subgroup.Conclusion Tacrolimus can reduce the number of inflammatory cells in prostatic tissue in EAP rat model,which may be related to its suppression of the production of IL-2 and activation of T cells.

Objective To study the relationship between the expression of sCD20 and the graft acute rejection,and the relationship between the level of sCD20 in peripheral blood and prognosis of the transplant kidney.Methods Fifty patients who had received renal transplantation from 2007 to 2010 were retrospectively reviewed.The expression of sCD20 in the blood was detected by enzyme linked immunosorbent assay (ELISA).Results The expression levels of sCD20 were higher in acute renal rejection group (1750.60±359.59) ng/L than those in non-rejection group (936.96 ± 181.71 ) ng/L before transplantation (P ＜0.05).After transplantation the expression levels of sCD20 were (2516.20 ±511.33) ng/L in acute renal rejection group and (988.40 ± 215.78 ) ng/L in non-rejection group ( P ＜ 0.05 ).Conclusion The expression of sCD20 in blood is correlated with clinical renal acute rejection and prognosis of the transplant kidney.

Laparoscopy-assisted distal gastrectomy for gastric cancer was first reported by Kitano et al. in 1994, but only for early gastric cancer. In 1997, laparoscopy-assisted D2 radical gastrectomy was performed for the first time by Goh et al. for the treatment of advanced gastric cancer and achieved good short-term efficacy, thus dramatically expanded its indications from early gastric cancer to advanced gastric cancer.

Objective To investigate the expression of Engrail-2 (EN2) and its significance in different prostate cancer cell lines and normal human prostate epithelial cell line.Methods The expression of EN2 was detected in prostate cancer cell lines (PC3,DU145,LNCAP) and normal prostate epithelial cell line RWPE-1 by using reverse transcription-polymerase chain reaction (RT-PCR),enzyme linked immunosorbent assay (ELISA) and immunofluorescence.Results The EN2 mRNA and protein expression levels in Pca cell lines ( LNCAP,PC3,DU145 ) were 1.65 ± 0.19/8.74 ± 0.34,1.08 ± 0.12/3.07 ±0.24,and 1.15 ±0.53/2.86± 0.26 respectively,which was significantly higher than in normal prostate epithelial cell line RWPE-1 (0.42 ± 0.11/0.86 ± 0.99 ) ( P ＜ 0.05 ).The EN2 level was higher in LNCAP cells than in PC3 and DU145 cells (P ＜ 0.05).Conclusion The expression of EN2 in 3 prostate cancer cell lines is higher than in RWPE-1 and EN2 protein can be secreted by prostate cancer cells.It is important for the further study on the EN2 potential roles in the occurrence and development of prostate carcinoma.