Identification of CD8+ T-cell epitope from multiple myeloma-specific antigen AKAP4

Multiple myeloma (MM) is a malignant plasma cell disorder affecting mainly the elderly population. Revolutionary progress in immunotherapy has been made recently, including monoclonal antibodies and chimeric antigen receptor T cell (CAR-T) therapies; however, the high relapse rate remains problematic. Therefore, combination therapies against different targets would be a reasonable strategy. In this study, we present a new X-chromosome encoded testis-cancer antigen (CTA) AKAP4 as a potential target for MM. AKAP4 is expressed in MM cell lines and MM primary malignant plasma cells. HLA-A*0201-restricted cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transduced with an adenovirus vector encoding the full-length AKAP4 gene were demonstrated to lyse AKAP4+ myeloma cells. Seven of the 12 candidate epitopes predicated by the BIMAS and SYFPEITH algorithms were able to bind HLA-A*0201 in the T2 binding assay, of which only two peptides were able to induce CTL cytotoxicity in the co-culture of peptide-loaded human mature dendritic cells and the autologous peripheral blood mononuclear cells (PBMCs) from the same HLA-A*0201 donor. The AKAP4 630–638 VLMLIQKLL was identified as the strongest CTL epitope by the human IFN-γ ELISPOT assay. Finally, the VLMLIQKLL-specific CTLs can lyse the HLA-A*0201+AKAP4+ myeloma cell line U266 in vitro, and inhibit tumor growth in the mice bearing U266 tumors in vivo. These results suggest that the VLMLIQKLL epitope could be used to develop cancer vaccine or T-cell receptor transgenic T cells (TCR-T) to kill myeloma cells

Age-associated developmental changes in the activated partial thromboplastin time (APTT) and causes of prolonged APTT values in healthy Chinese children

Background: The concept of developmental hemostasis has been universally accepted. Physiological reference ranges for coagulation tests are available for infants and children of different ages. However, on Oriental children they are rare. Methods: Results of preoperative activated partial thromboplastin time (APTT) in neonates, infants, children aged 1–18 years and adults with minor elective surgery in a university affiliated hospital were reviewed retrospectively. Plasma activity of factors VIII, IX, XI, XII (FVIII:C, FIX:C, FXI:C, FXII:C) and lupus anticoagulants (LAC) in 47 children with prolonged APTT and 34 adult controls were measured to investigate the causes of prolongation. Results: Compared with adults, APTT values were prolonged significantly and were age-dependent in children, especially in neonates and infants aged 1–6 months. Mean values for FXII:C and FIX:C in children with prolonged APTT values were significantly lower than those in adults (p<0.001). Prolonged APTT values correlated negatively with FXII:C and FIX:C, and weakly with the LAC Screen ratio (LAC-SR) (r0.01=−0.808, –0.705 and 0.372, p=0.000, 0.000 and 0.001, respectively). There was weak negative correlation between FXII:C and LAC-SR (r0.01=−0.277, p=0.012). No significant correlation was seen between prolonged APTT values and FVIII:C or FXI:C. Conclusions: APTT values change dynamically with age during childhood and display a distinct pattern of evolution in children. Lower values of FXII:C and FIX:C, and presence of LAC contribute to the prolongation of APTT values in Chinese children. Clin Chem Lab Med 2009;47:1531–7.Peer Reviewe

The Potential Genes Mediate the Pathogenicity of Allogeneic CD4+T Cell in aGVHD Mouse Model

Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4+ lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4+T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD

Automatic road extraction from mobile laser scanning data

Abstract—Extraction of road surface and boundary is essential for autonomous vehicle navigation, road monitoring and important scene structures extraction. Mobile laser scanning (MLS) technology as a new information acquiring manner can quickly scan the whole scene and provide density and accurate 3D coordinate data and other information such as trajectory, color and reflectance. In this paper an automatic road extraction method is proposed based on trajectory information from mobile laser scanning data. Through the trajectory, location and approximated direction of local road patch could be determined. Searching algorithm is applied along the approximated road direction and the orthogonal direction. To determine the road boundary a hypothesis testing method based on local altitude variance is used. To filter false boundary points, local altitude mean value is applied. Experiment results demonstrate the reliability of the proposed algorithm for automatic road surface and boundary extraction. Keywords-mobile laser scanning (MLS); road extraction; trajectory I

Automatic road extraction from mobile laser scanning data

Conference Name:2012 International Conference on Computer Vision in Remote Sensing, CVRS 2012. Conference Address: Xiamen, China. Time:December 16, 2012 - December 18, 2012.Xiamen University; National University of Defense TechnologyExtraction of road surface and boundary is essential for autonomous vehicle navigation, road monitoring and important scene structures extraction. Mobile laser scanning (MLS) technology as a new information acquiring manner can quickly scan the whole scene and provide density and accurate 3D coordinate data and other information such as trajectory, color and reflectance. In this paper an automatic road extraction method is proposed based on trajectory information from mobile laser scanning data. Through the trajectory, location and approximated direction of local road patch could be determined. Searching algorithm is applied along the approximated road direction and the orthogonal direction. To determine the road boundary, a hypothesis testing method based on local altitude variance is used. To filter false boundary points, local altitude mean value is applied. Experiment results demonstrate the reliability of the proposed algorithm for automatic road surface and boundary extraction. 漏 2012 IEEE

Epidemiology, Management, and Outcome of Invasive Fungal Disease in Patients Undergoing Hematopoietic Stem Cell Transplantation in China: A Multicenter Prospective Observational Study

AbstractThe China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm3 for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather than autologous (17 of 348; 4.9%) HSCT and was significantly higher in patients receiving pre-emptive (18.6%) rather than empirical (6.1%) or targeted (9.5%) antifungal therapy (P = .002). Improvements in the selection and timing of prophylactic antifungals would be welcome. Health care providers should remain alert to the increased risk of IFD and associated mortality in allogeneic HSCT recipients and the ongoing risk of IFD even after discharge from the hospital

Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world

Abstract Background Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable‐risk by European Leukemia Net (ELN), CBF‐AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF‐AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. Methods Retrospective analysis of 149 AML patients (75 CBF‐AML, 74 non‐CBF) at Peking University First Hospital (March 2012–March 2022). Results CBF‐AML patients have significantly lower disease‐free survival (DFS) (p = 0.005) and higher non‐relapse mortality (NRM) (p = 0.028) compared to non‐CBF AML. inv (16) and t(8;21) show distinct co‐occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) improves prognosis in low‐risk t(8;21). Conclusion Prognosis of CBF‐AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo‐HSCT may benefit low‐risk t(8;21), but further research is needed for conclusive evidence

PEG-asparaginase in BFM-90 regimen improves outcomes in adults with newly diagnosed lymphoblastic lymphoma

Objective:Although L-asparaginase (L-ASP) is a standard treatment for lymphoblastic lymphoma (LBL),hypersensitivity reactions by some patents limit its application.Polyethylene glycol-conjugated asparaginase (PEGASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia (ALL).In this study,we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90 regimen (PEG-ASP-BFM-90) for adult LBL.Methods:Between June 2012 and July 2015,we treated 30 adult patients with newly diagnosed LBL,using PEGASP-BFM-90 in a prospective,multicenter and single-arm clinical study at 5 participating institutions in China.Results:All the 30 patients,including 19 males and 11 females with a median age of 30 (range:18-62) years,completed 128 times of the PEG-ASP,with the median of 4 (range:2-6) times.Patients did not receive radiotherapy at this time.The overall response rate was 86.7％ (26/30),vith 50.0％ (15/30) complete response and 36.7％ (11/30) partial rcsponsc.Thc 3-year overall survival was 46.0％ [95％ confidence interval (95％ CI),28.2％-64.8％],and the 3-year progression-free survival was 43.0％ (95％ CI,25.7％-62.0％).Major adverse events were myelosuppression,reduced fibrinogen,liver dysfunction and digestive tract toxicities.No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions:Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90,with predominantly grade 3-4 neutropenia for adult LBL,and no therapyrelated deaths.The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL.Major advantages include less serious allergic reactions,2-3 weeks of action duration,and convenience for patients and physicians.Objective:Although L-asparaginase (L-ASP) is a standard treatment for lymphoblastic lymphoma (LBL),hypersensitivity reactions by some patents limit its application.Polyethylene glycol-conjugated asparaginase (PEGASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia (ALL).In this study,we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90 regimen (PEG-ASP-BFM-90) for adult LBL.Methods:Between June 2012 and July 2015,we treated 30 adult patients with newly diagnosed LBL,using PEGASP-BFM-90 in a prospective,multicenter and single-arm clinical study at 5 participating institutions in China.Results:All the 30 patients,including 19 males and 11 females with a median age of 30 (range:18-62) years,completed 128 times of the PEG-ASP,with the median of 4 (range:2-6) times.Patients did not receive radiotherapy at this time.The overall response rate was 86.7％ (26/30),vith 50.0％ (15/30) complete response and 36.7％ (11/30) partial rcsponsc.Thc 3-year overall survival was 46.0％ [95％ confidence interval (95％ CI),28.2％-64.8％],and the 3-year progression-free survival was 43.0％ (95％ CI,25.7％-62.0％).Major adverse events were myelosuppression,reduced fibrinogen,liver dysfunction and digestive tract toxicities.No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions:Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90,with predominantly grade 3-4 neutropenia for adult LBL,and no therapyrelated deaths.The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL.Major advantages include less serious allergic reactions,2-3 weeks of action duration,and convenience for patients and physicians.SCI(E)中国科学引文数据库(CSCD)166-742