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Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo‐HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3‐ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single‐arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI‐associated pancytopenia was observed. The cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (GVHD) at 100 days post‐DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non‐relapse mortality and relapse at 3 years post‐DLI were 21.6%, 25.0% and 26.1%, respectively. The 3‐year relapse‐free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo‐HSCT in patients with unfavourable gene mutations., This prospective, single‐arm, pilot study investigated the efficacy and feasibility of prophylactic DLI and showed that prophylactic DLI could effectively prevent relapse without increasing the incidence of GVHD or NRM for patients with unfavourable gene mutations after allo‐HSCT. In addition, prophylactic decitabine followed by DLI showed potential safety and efficacy without impact on hematologic reconstitution and with acceptable incidence of DLI‐related aGVHD.

Background: Restless legs syndrome (RLS) is a common neurological disorder with unpleasant leg sensations and serious negative effects on mental and physical health. Many observational studies showed that people with RLS had a high risk of vascular diseases, including cerebrovascular and cardiovascular diseases (CVD), but the findings were conflicting. The Jidong RLS Cohort Study is a prospective cohort study designed to mainly examine whether or not RLS is associated with an increased risk of CVD.Methods and Design: The study recruited 8,867 healthy participants older than 18 years from October 2014 to December 2015. Participants received a physical examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Restless legs syndrome was assessed using the international RLS diagnostic criteria. All of subjects would be followed up until December 2025. Major cardiovascular/cerebrovascular events including cardiac death, myocardial infarction, ischemic heart disease, heart failure, atrial fibrillation, ischemic, and hemorrhagic stroke will be the primary outcomes. Secondary outcomes include all-cause mortality, the decline in quality of life, cognitive impairment, and depression.Discussion: This study will contribute to the scientific evidence on the association between RLS and cardiovascular risks and also provide an unprecedented opportunity for early detection and prevention of CVD.

Metastasis is the main cause of colon cancer‐related deaths. RBP‐Jκ is involved in colon cancer development, but its function in colon cancer metastasis is still unclear. Tumour‐associated macrophages are the main cell components in tumour microenvironments. Here, we aimed to determine the function of RBP‐Jκ in colon cancer metastasis and its underlying mechanisms for modulating interactions between colon cancer cell and tumour‐associated macrophages. Through bioinformation analysis, we found that RBP‐Jκ was overexpressed in colon cancer tissues and associated with advanced colon cancer phenotypes, macrophage infiltration and shorter survival overall as confirmed by our patients’ data. And our patients’ data show that RBP‐Jκ expression and tumour‐associated macrophages infiltration are associated with colon cancer metastasis and are independent prognostic factors for colon cancer patients. Tumour‐associated macrophages induced colon cancer cell migration, invasion and epithelial‐mesenchymal transition through secreting TGF‐β1. Colon cancer cells with high RBP‐Jκ expression induced the expression of TGF‐β1 in tumour‐associated macrophages by secreting CXCL11. Our research revealed that colon cancer cells secreted CXCL11 via overexpression of RBP‐Jκ to enhance the expression of TGF‐β1 in tumour‐associated macrophages to further promote metastasis of colon cancer cells.

Donor lymphocyte infusion (DLI) might be used prophylactically to reduce relapse after allogeneic hematopoietic stem cell transplantation for very high-risk leukemia/lymphoma without effective targeted therapy. To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective analysis in a cohort of 21 HID-SCT and 13 MSD-SCT recipients, displaying similar baseline characteristics except for donor's gender distribution. Grade 2-4 acute graft-versus-host disease (GVHD) at 100-day post-DLI was higher in HID-SCT group than that in MSD-SCT group (59.5% vs. 30.8%, p = 0.05). The grade 3-4 acute GVHD (17.5% vs. 7.7%), 1-year chronic GVHD (36.6% vs. 33.2%), and severe chronic GVHD (15.3% vs. 27.3%) were not statistically significant different between groups. One-year non-relapse mortality was higher in HID-SCT group than that in MSD-SCT group with marginal significance (27.9% vs. 0.0%, p = 0.061). One-year relapse rate was not statistically significant different between HID-SCT group and MSD-SCT group (21.6% vs. 36.5%, p = 0.543). For HID-SCT recipients, 1-year relapse rate was lower in patients receiving prophylactic DLI than that in a control cohort of eight patients with same very high-risk features but not receiving prophylactic DLI (62.5% vs. 28.3%, p = 0.037). No statistically significant difference was observed in 1-year overall survival (OS, 55.1% vs. 83.9%, p = 0.325) and relapse-free survival (RFS, 50.1% vs. 74.0%, p = 0.419) rates between HID-SCT group and MSD-SCT group. In multivariate analyses, non-remission status prior to transplant, poor-risk gene mutations, and donor's age ≥ 48 years predicted a higher risk of relapse after DLI. Non-remission status prior to transplant predicted inferior OS and RFS. Patient's age ≥ 40 years also predicted an inferior OS. In conclusion, prophylactic DLI was very safe and efficient for reducing relapse in patients with very high-risk AML receiving MSD-SCT. In the recipients of HID-SCT, the application of prophylactic DLI could reduce the risk of relapse, although with a higher incidence of DLI-associated acute GVHD than those of MSD-SCT.

There was limited information about the efficacy of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in non-complete remission (non-CR) patients with relapsed/refractory peripheral T cell lymphomas (PTCLs). We conducted a retrospective study of 21 consecutive non-CR patients with relapsed/refractory PTCLs who received myeloablative allo-PBSCT between January 2008 and June 2016. The median follow-up of survivors was 46.5 months (range, 14-105 months). The estimated 3-year relapse rate was 24% (95% CI, 9 to 43%). The 3-year non-relapsed mortality rate was 24% (95% CI, 9 to 44%). Overall, the estimated 3-year overall survival was 47% (95% CI, 25 to 66%). And the estimated 3-year progression-free survival was 46% (95% CI, 24 to 66%). Specifically, eight patients failed to achieve a CR at the first evaluation 3 months after allo-PBSCT and received withdraw of immunosuppression. Five patients also received donor lymphocytes infusions. Five (5/8, 62.5%) patients responded subsequently to these interventions (complete = 4, partial = 1). Overall, ten patients were alive at our last follow-ups, and durable CR were achieved in nine patients without further therapy. Five (50%) of these ten alive patients experienced chronic graft-versus-host disease (GVHD). Our favorable clinical outcomes suggested myeloablative allo-PBSCT was a valid therapeutic option for non-CR patients with relapsed/refractory PTCLs. The sustained CR after immunotherapeutic intervention and high prevalence of chronic GVHD in alive patients provided evidence of graft versus T cell lymphoma effects.

During the vibration of a transmission tower, the joints will be subjected to a reciprocating load. To obtain the accurate state of the transmission tower under the load, the mechanical properties of the joints under the vibration load must be considered. In this paper, the mechanical properties of typical K-joints in transmission tower structures are studied by numerical simulation. The failure mode of the K-joint under cyclic loading is also analyzed. The mechanical properties of the K-joint are discussed from the aspects of hysteretic characteristics, stiffness degradation, energy dissipation capacity, and ductility evaluation, and the influencing factors are discussed. The results show that the failure mode of the K-joint is related to the bolt grade and steel strength. When analyzing K-joints, the moment-rotation hysteresis curve should be combined with the realistic parameters of joints to consider the hysteretic behavior of the K-joint. The results provide a theoretical reference for the accurate modeling of transmission towers.

Meng-jie Liu, Hui Guo, Li-li Jiang, Min Jiao, Shu-hong Wang, Tao Tian, Xiao Fu, Wen-juan Wang Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Wen-juan WangDepartment of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi, People’s Republic of ChinaTel +86 15829235823Fax +86 29 85324086Email lingyinnancy@163.comIntroduction: This study aims at exploring the expression and significance of recombination signal-binding protein for immunoglobulin kappa J region (RBP-Jκ) and C-X-C motif chemokine 11 (CXCL11) in human colon cancer tissues.Methods: The RBP-Jκ and CXCL11 expression levels were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) in patients with colon cancer, and their prognostic significance was evaluated.Results: Through analyzing 342 samples of colon cancer patients treated at our institution, increased expression of RBP-Jκ and CXCL11 was found in human colon cancer specimens compared with matched paratumorous normal specimens (P< 0.001). A positive correlation was found between RBP-Jκ expression and CXCL11 expression (P< 0.001). High RBP-Jκ expression was significantly associated with poorly differentiated tumors (P=0.005), invasion beyond propria muscularis (P=0.025), lymph node metastases (P=0.005), distant metastasis (P< 0.001), advanced tumor-node-metastasis (TNM) stage (P=0.004), and a shorter overall survival (P< 0.001). An increase in CXCL11 protein expression was associated with poorly differentiated tumors (P=0.015), invasion beyond propria muscularis (P=0.029), lymph node metastases (P=0.031), distant metastasis (P=0.045), advanced TNM stage (P=0.026), and a shorter overall survival of patients (P< 0.001). In multivariate Cox regression analysis, RBP-Jκ protein expression (P=0.036), CXCL11 protein expression (P=0.001), differentiation (P< 0.001), depth of invasion (P=0.009), distant metastasis (P< 0.001), and TNM stage (P< 0.001) were independent prognostic indicators of colon cancer.Conclusion: High expression of RBP-Jκ is closely associated with high CXCL11 expression, which represents a risk factor for the poor overall survival of colon cancer patients.Keywords: RBP-Jκ, CXCL11, prognosis, colon cancer

Background: The sequence effect (SE), referring to step-to-step reduction in amplitude, is considered to lead to freezing of gait (FOG) in Parkinson's disease (PD). Visual cues may alleviate SE and help reduce freezing episodes. FOG patients show significant SE prior to turning or toward a doorway, but the SE toward a destination has not been clearly studied. Objectives: To examine the SE when approaching a destination in PD patients with FOG, and to further explore the effects of different types of visual cues on destination SE. Methods: Thirty-five PD patients were divided into a freezing (PD+FOG, n = 15) group and a non-freezing (PD–FOG, n = 20) group. Walking trials were tested under three conditions, including without cues (no-cue condition), with wearable laser lights (laser condition), and with transverse strips placed on the floor (strip condition). Kinematic data was recorded by a portable Inertial Measurement Unit (IMU) system. The destination SE and some key gait parameters were evaluated. Results: The PD+FOG group showed greater destination SE in the no-cue and laser conditions when compared to the PD–FOG group. There were no significant differences in the strip condition when comparing destination SE of the two groups. The destination SE was alleviated only by using the transverse strips on the floor. In contrast, transverse strips and wearable laser lights could increase the step length. Conclusions: The significant destination SE may explain why FOG patients are prone to freezing when heading toward their destination. Visual cues using transverse strips on the floor may be a more effective strategy for FOG rehabilitation in PD patients.

Corticosteroids are commonly used as first-line treatment for acute graft-versus-host disease (aGVHD); however, they are effective in only approximately one-half of patients. This study prospectively evaluated the use of ruxolitinib combined with 1 mg/kg methylprednisolone in the initial treatment of aGVHD. A total of 32 patients were enrolled. aGVHD involved the skin (53.1%), gastrointestinal tract (68.8%), and liver (6.0%). The complete response rate at day +28 was 96.9%. The 1-year and 2-year cumulative incidence rates of chronic GVHD were 9.4% and 13.8%, respectively. The 1- year cumulative incidence of nonrelapse mortality was 8.7%, and the Kaplan-Meier curve estimated 1-year overall survival after transplantation at 73.4%. This prospective study suggests that patients with aGVHD show a high response rate to ruxolitinib (5 mg/day) combined with 1 mg/kg/day methylprednisolone. This novel regimen was seen to spare steroid exposure, alleviate toxicity, and improve long-term survival.

In allogeneic hematopoietic stem cell transplantation recipients, cytomegalovirus (CMV) infection can cause overt CMV-associated disease, which is a main cause of transplantation-associated mortality. CMV infection correlates closely with donor's type. We therefore examined whether risk factors of CMV reactivation and clinical endpoints in patients with hematologic malignancies after allogeneic peripheral blood stem cell transplantation (PBSCT) differed between using matched-sibling donors (MSD-SCT) and haploidentical donors (HID-SCT). In this retrospective cohort study, we enrolled in 200 consecutive patients received an unmanipulated G-CSF-mobilized allogeneic PBSCT. Ninety (45%) patients received MSD-SCT and 110 (55%) received HID-SCT. Quantitative PCR was used for monitoring of CMV reactivation after transplantation. One-year cumulative incidence of CMV DNAemia was 55.0%, ranging from 23.5% in MSD-SCT group to 81.0% in HID-SCT group (p 0.001). Although univariate analyses showed that non-myeloid malignancies, disease in complete remission status at transplantation, pretreatment with antithymocyte globulin, HLA-haploidentical donors, male donors, previous Epstein-Barr virus DNAemia, and absolute lymphocyte count on day 30 0.6 × 10

Unmanipulated haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2, and DNMT3a. In this study, we aimed to establish the tolerance and efficacy of prophylactic donor lymphocyte infusion (DLI) with G-CSF-primed peripheral blood progenitors for prevention of relapse in these very high-risk patients after haplo-PBSCT. The prophylactic DLI was given at a median of 77 days after transplantation in 31 of 45 consecutive patients with very high-risk leukemia/lymphoma. The median dose of CD3+ cells for infusion was 1.8 × 107/kg. The 100-day incidences of acute graft-versus-host disease (GVHD) grades 2–4 and 3–4 after DLI were 55.3% and 10.2%. The 2-year incidences of chronic GVHD and severe chronic GVHD were 52.0% and 18.2%. The 2-year incidences of non-relapse mortality and relapse were 33.1% and 32.5%. The 2-year probabilities of overall survival and relapse-free survival were 40.1% and 31.9%. Poor-risk gene mutations (p = 0.029), disease in non-remission status prior to transplantation (p = 0.005), and donors older than 40 years of age (p = 0.043) were associated with relapse after DLI. In multivariate analysis, disease in non-remission status prior to transplantation was an independent risk factor of relapse (hazard ratio = 4.079; p = 0.035). These data showed the feasibility of the prophylactic DLI in the haplo-PBSCT setting and the anti-leukemic efficacy in very high-risk leukemia/lymphoma. Electronic supplementary material The online version of this article (10.1007/s00277-018-3482-7) contains supplementary material, which is available to authorized users.

Background Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients with haematological malignancies. Aim To evaluate the efficacy and rationality of primary antifungal prophylaxis (PAP) in a 5-year real-life setting and choose an appropriate PAP strategy. Methods Clinical data of patients were retrospectively reviewed and IFD was diagnosed using the revised diagnostic criteria. The efficacy of PAP and the risk factors for IFD, especially the rationality of PAP, were evaluated. Results Of the 1340 patients enrolled, 749 patients received PAP (55.9%), and IFD occurred in 157 patients: 51 (6.8%) in the PAP group and 106 (17.9%) in the non-PAP group (P = 0.000). The IFD-related mortality was 10.1 and 29.7% in the PAP group and non-PAP group (P = 0.000) respectively. PAP was an independent protective factor for IFD (odds ratio = 0.183, 95% confidence interval: 0.122-0.274, P = 0.000) and could reduce the effect of risk factors, such as allogeneic haemopoietic stem cell transplantation, prolonged neutropenia and corticosteroid. The IFD incidence was not significantly different among different PAP regimens and PAP start time subgroups, and it was lowest (4.2%) when PAP started after a short period of neutropenia (1-10 days). Conclusion PAP is necessary and efficient to prevent IFD in haematological patients, and the real-life PAP strategy is reasonable. Different drugs can be chosen, and it is better to start PAP as soon as neutropenia begins.

// Ya-Huan Guo 1, 2, * , Hai-Feng Sun 1, 3, * , Yan-Bing Zhang 2 , Zi-Jun Liao 1, 2 , Lei Zhao 4 , Jie Cui 5 , Tao Wu 1 , Jian-Rong Lu 1 , Ke-Jun Nan 1 , Shu-Hong Wang 1 1 Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China 2 First Department of Medical Oncology, Shaanxi Provincial Tumor Hospital, Xi’an, P.R. China 3 Third Department of Medical Oncology, Shaanxi Provincial Tumor Hospital, Xi’an, P.R. China 4 Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA 5 Department of Oncology, Yan’an University Affiliated Hospital, Yan’an, P.R. China 6 Third Department of Pathology, Shaanxi Provincial Tumor Hospital, Xi’an, P.R. China * These authors share the first authorship Correspondence to: Ke-Jun Nan, email: nankj@163.com Shu-Hong Wang, email: wsh2003@126.com Keywords: platelet/lymphocyte ratio, lymphocyte/monocyte ratio, colorectal cancer, prognostic predictor, inflammatory markers Received: August 23, 2016 Accepted: December 28, 2016 Published: February 14, 2017 ABSTRACT Background: Conflicting evidence exists regarding the effects of platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio(LMR) on the prognosis of colorectal cancer (CRC) patients. This study aimed to evaluate the roles of the PLR and LMR in predicting the prognosis of CRC patients via meta-analysis. Methods: Eligible studies were retrieved from the PubMed, Embase,andChina National Knowledge Infrastructure (CNKI) databases, supplemented by a manual search of references from retrieved articles. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated using the generic inverse variance and random-effect model to evaluate the association of PLR and LMR with prognostic variables in CRC, including overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Results: Thirty-three studies containing 15,404 patients met criteria for inclusion. Pooled analysis suggested that elevated PLR was associated with poorer OS (pooled HR = 1.57, 95% CI: 1.41 – 1.75, p < 0.00001, I 2 =26%) and DFS (pooled HR = 1.58, 95% CI: 1.31 – 1.92, p < 0.00001, I 2 =66%). Conversely, high LMR correlated with more favorable OS (pooled HR = 0.59, 95% CI: 0.50 – 0.68, p < 0.00001, I 2 =44%), CSS (pooled HR = 0.54, 95% CI: 0.40 – 0.72, p < 0.00001, I 2 =11%) and DFS (pooled HR = 0.82, 95% CI: 0.71– 0.94, p =0.005, I 2 =29%). Conclusions: Elevated PLR was associated with poor prognosis, while high LMR correlated with more favorable outcomes in CRC patients. Pretreatment PLR and LMR could serve as prognostic predictors in CRC patients.

The optimal rabbit anti-thymocyte globulin (rATG) graft-versus-host disease (GVHD) prophylaxis regimen in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT) remains to be elucidated. In this prospective study, we used low-dose rATG for GVHD prophylaxis in patients or donors aged ≥ 40 years with hematological malignancies receiving MSD-PBSCT. rATG was administered to 40 patients at an intravenous dose of 5 mg/kg divided over day 5 and day 4 before graft infusion. No graft failure occurred. Median times to leukocyte engraftment and platelet engraftment were 11.0 days and 13.9 days. The cumulative incidence of grades 2–4 and grades 3–4 acute GVHD at day +100 was 30.0% and 2.6%. The 2-year cumulative incidence of extensive chronic GVHD and severe chronic GVHD was 11.4% and 14.7%. 93.5% (29/31) of patients had discontinued immunosuppressive medication within 3 years after transplantation. The 2-year cumulative incidence of transplant-related mortality (TRM) and relapse was 14.0% and 22.6%. The cumulative incidence of cytomegalovirus reactivation, Epstein–Barr virus reactivation, and fungal infection was 22.3%, 12.9%, and 12.5%. Kaplan–Meier estimates for overall survival, disease-free survival, and GVHD-free and relapse-free survival 3 years after transplantation were 68.9%, 68.9%, and 54.0%. rATG for GVHD prophylaxis is tolerable and efficacious at a 5 mg/kg total dose administered over 2 days (days −5 to −4) in patients receiving allogeneic MSD-PBSCT.

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein–Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p

Conductors with sector-shaped ice are susceptible to galloping. To prevent and control galloping, it is necessary to study the conductor aerodynamic characteristics. Wind tunnel tests were performed to study the influence of two shape parameters (ice thickness and ice angle) of a conductor with sector-shaped ice on the aerodynamic characteristics considering the roughness of the surface. In addition, the unstable areas for galloping are discussed according to Den Hartog theory and Nigol theory. The results show that with increasing ice thickness, the aerodynamic coefficient curves fluctuate more strongly, and galloping tends to occur; with increasing ice angle, the unstable area becomes larger according to Nigol theory, and the increasing drag coefficient will suppress the unstable areas according to Den Hartog theory. With the increasing two shape parameters, the most affected ranges of the aerodynamic coefficient curves are 150–180∘.

Background Multidrug resistance is the main obstacle for hepatocellular carcinoma (HCC) treatment. miR-32-5p is involved in HCC progression but its function in multidrug resistance is still unclear. Here we aim to find out the function of miR-32-5p in inducing multidrug resistance and its underlying mechanisms of transforming sensitive cell to resistant cell. Methods We detected the expression of miR-32-5p and PTEN in the multidrug-resistant cell line (Bel/5-FU) and the sensitive cell line (Bel7402), HCC and para-carcinoma liver tissues through real-time PCR. Dual-luciferase reporter assay verified PTEN is the target of miR-32-5p. Exosomes from sensitive and multidrug resistant cell line were obtained and confirmed through ultracentrifuge and Nano Analyzer. Gain- and loss-of-function experiments, rescue experiments, a PI3K/Akt pathway inhibitor, an exosome biogenesis inhibitor, and nude mice xenograft models were used to determine the underlying mechanisms of miR-32-5p and PTEN, as well as exosomal miR-32-5p in inducing multidrug resistance in vitro and in vivo. Results miR-32-5p was significantly elevated but PTEN was reduced in Bel/5-FU. An inverse correlation between miR-32-5p and PTEN was confirmed in HCC cell lines and patients; moreover, high expression of miR-32-5p and low expression of PTEN were positively associated with poor prognosis. Over-expression of miR-32-5p activated the PI3K/Akt pathway by suppressing PTEN and induced multidrug resistance via exosomes through promoting angiogenesis and epithelial-mesenchymal transition (EMT). Conclusions Our study demonstrated that the multidrug-resistant cell, Bel/5-FU delivers miR-32-5p to sensitive cell, Bel7402 by exosomes and activates the PI3K/Akt pathway to further induce multidrug resistance by modulating angiogenesis and EMT. Electronic supplementary material The online version of this article (10.1186/s13046-018-0677-7) contains supplementary material, which is available to authorized users.

Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids. The levels of β1 integrin and the effects on the focal adhesion kinase (FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis, immunofluorescence and flow cytometry. The role of β1 integrin was confirmed by using an inhibitory antibody. Results Cell proliferation inhibition and cell apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids compared with monolayer cells. There were high levels of β1 integrin in multicellular spheroids. β1 integrin inhibitory antibody prevented the formation of multicellular spheroids, coupled with a significant increase in proliferation inhibition and apoptosis induction. β1 integrin inhibitory antibody effectively suppressed activation of both FAK and Akt in multicellular spheroids. Conclusions β1 integrin mediated multicellular drug resistance through the FAK/Akt pathway in HCC spheroids.

The comparative efficacy and safety of antithymocyte globulin (ATG) at fixed doses in patients undergoing allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. In this study, the records of 56 patients and 54 patients who received pre-transplant ATG-Thymoglobulin (ATG-T) at a total dose of 10 mg/kg and ATG- Fresenius (ATG-F) at a total dose of 20 mg/kg, respectively, were retrospectively analyzed. ATG-F patients had a significantly lower probability of developing chronic graft-vs-host disease (cGVHD) than those treated with ATG-T (p = 0.04). ATG-F was associated with a non-significant trend towards lower relapse rates and higher survival at 3- and 5-years of follow-up compared with ATG-T. A significantly greater proportion of ATG-T patients experienced chills and high fever than ATG-F patients (p < 0.01). The current findings suggest that ATG-F may more effectively and safely prevent cGVHD without increasing relapse rates in patients undergoing UR-PBSCT.

Evidences suggested that combined blockade of the VEGF and EGFR pathways can improve the treatment efficacy of non-small-cell lung cancer (NSCLC). In our previously clinical practice, we observed that thalidomide, a potent VEGF inhibitor, can significantly decrease the tumor size of one EGFR-TKI resistance patient with lung cancer cachexia. In this pilot study, we tried to assess the efficacy and toxicity of the combination therapy of erlotinib and thalidomide in advanced NSCLC patients with acquired resistance to erlotinib. In all, 52 NSCLC patients with drug resistance to erlotinib were recruited and treated with this combination therapy. After treatment, 4 patients presented with partial remission (PR), 16 with stable disease (SD) and 32 with progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) was 7.7% and 38.5%, respectively. In this study, we firstly confirmed that thalidomide can reversion of erlotinib-acquired resistance with a 7 weeks median progression-free survival (PFS); besides, this combination therapy shows acceptable drug tolerance; the most common drug related adverse events were astriction, numbness and sleeve-like feeling in the limbs, no thrombosis occurred in any patient. Those evidences indicate that thalidomide may be a useful candidate for reversion of erlotinib-acquired resistance.

Aberrant expression of microRNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. microRNA-219-5p (miR-219-5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR-219-5p and colorectal cancer (CRC) metastasis remains unclear. In the present study, miR-219-5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer-binding factor 1 (LEF1) as a direct target of miR-219-5p. Overexpression of miR-219-5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial-mesenchymal transition (EMT). Furthermore, silencing LEF1 phenocopied this metastasis-suppressive function. The recovery experiment showed that re-expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR-219-5p. Additionally, we demonstrated that miR-219-5p exerted this tumor-suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR-219-5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR-219-5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.

Kinematics parameters calculation is the basis of piston pump design and performance analysis. Taking an axial piston pump with incline piston and spherical swash plate as the research object, Aimed at the deficiency of current formula for calculating piston pump kinematics parameters which included displacement, velocity and acceleration. In this paper, according to piston pump part motion geometry relationship, a correction kinematics algorithm is deduced by using the the spherical coordinate and cartesian coordinate transformation method, the analyse method and deduction procedure ensure the new calculating formula are precise in theory. Applying the calculating formula to an aero engine fuel axial piston pump, results show that. The displacement, velocity, acceleration according to the kinematics principle of piston pump, it can be used in the kind of piston pump kinematics parameters calculation and current calculating method evaluation.

With the development of the aero engine control technique, aero fuel centrifugal pump with integrated inducer and impeller meet the requirements better than the divided pump. This paper established the hybrid network of the centrifugal pump which adopted multi-block topology structure and octree format, analyzed the internal flow field performance of the pump based on numerical simulation. The simulation datas compared with test datas show that under different calculation conditions, head error of the simulation data and experimental data is less than 1%, and the efficiency value of error is less than 5%. The simulation method can accurately calculate the performance of the pump. The simulation analysis shows that the asymmetry of the impeller internal pressure is appreciable under different flow conditions because of the inlet length, under other small flow conditions. The most dramatic change is the pressure in the impeller channel, and the pressure under large flow conditions is lower than that under other flow conditions. In fixed location of the pressure side, there may produce low speed flow group, the situation is the same as in the entrance to the attachment of back pressure side.

A inducer and impeller combination aero fuel centrifugal pump design method was given. Based on empirical coefficient method the preliminary structural parameters of the combination Centrifugal pump were designed firstly. Then the Centrifugal pump Hybrid Grid model was built with muti-block structure and octree style.The final structure parameters were obtained by CFD numerical simulation optimization. Finally, the flow field of combination Centrifugal pump was analyzed and compared simulation datas with test datas by making the test samples.The relative error of the design point doesn’t exceed 5%, indicates that the inducer and impeller combination pump meet the design requirements.

To solve the problem that single stage booster pump has the problem of low oil pressure at low speed condition. Paper gave a design method for three stage combination vortex pump which uses radial series. The preliminary structural parameters of the vortex pump were designed by using the empirical coefficient method. Then Hex/Wedge grid is used to generate mesh for the established 3D model of the vortex pump. The final structure parameters were obtained by CFD numerical simulation optimization iterately. Finally, the flow field of combination vortex pump was analyzed. Simulation results show that: The combination vortex pump meet the design requirements.

With the comprehensive implementation of construction of new socialist countryside, a large number of studies and researches relating to new rural construction planning have been emerged. How to build the program of road network with local characteristics, which are based on reality of the situation and adapted to the future development, the author probed into this issue with the example of road planning of Shengying Village, Yaodian Town, Dengzhou City, Henan Province. And the author has worked out a number of road planning experiences for sustainable development of countryside construction.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high-risk hematologic patients due to the absence of HLA-matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies. STUDY DESIGN AND METHODS: Patients who underwent unmanipulated HLA-mismatched/haploidentical PBSCT from July 2007 to March 2010 with high-risk hematologic malignancies were enrolled for retrospective analysis. RESULTS: Twenty-one patients with high-risk hematologic malignancies underwent unmanipulated HLA-mismatched/haploidentical PBSCT with myeloablative conditioning. The numbers of CD34+ cells infused at transplantation were 4.81 (range, 2.61-11.47) × 106/kg. Patients achieved myeloid and platelet engraftment at a median of 16.5 and 20 days, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) on Day 100 was 52.7 ± 10.7%, and the 2-year cumulative incidence of chronic GVHD was 39.5 ± 10.6%. The cumulative incidences of cytomegalovirus antigenemia and hemorrhagic cystitis within 100 days after PBSCT were 59.5 ± 16.7 and 34.8 ± 13.3%, respectively. One hundred-day transplantation-related mortality (TRM) rate and the 2-year cumulative TRM rate were 14.3 and 20.5 ± 7.8%, respectively. The 2-year cumulative overall survival was 62.1 ± 11.4% and the probability of disease-free survival at 2 years was 55.6 ± 10.7% with a 16-month median follow-up. CONCLUSION: Unmanipulated PBSCT is a promising protocol in HLA-mismatched/haploidentical transplant settings.

As that of coordination and ISO 15288, discipline system engineering and software engineering processes, methods have a lot in common, and concerns. In most of the system software interest, now offers an important function, more and more is the most significant factors determine the non-functional attributes. In the implementation of the system collection and failure are often attributed to the system and/or software engineering recovery. Need to use systems engineering software design and development, and need to incorporate software engineering concepts into system engineering, suggests that the decision of the two disciplines the close relationship between is appropriate. This article describes a definite theory integrating the two disciplines, defines a framework on establishing a vocabulary integration, and gives the use of this framework preliminary results to describe the system and software integration of defense plans.

The security of many emerging applications is based on broadcast encryption scheme, for example teleconference, pay-TV, etc. This Paper detailed analyzes the scenario of Cable TV, comprehensively studies the mostly all proposed broadcast encryption schemes. Finally we improved and enhanced the main broadcast encryption schemes so that they can be adapted by Cable TV.

Nasal NK/T-cell lymphoma is rare and occurs most frequently in East Asia and Latin America. It is characterized by its aggressive nature and tends to become resistant to chemotherapy and radiotherapy. Autologous haematopoietic stem cell transplantation (auto-HSCT) is often associated with a high relapse rate for the active or disseminated disease. There are limited data about allogeneic haematopoietic stem cell transplantation (allo-HSCT) for relapsed or refractory nasal NK/T-cell lymphoma. In our study, two patients with nasal NK/T-cell lymphoma were successfully treated with allo-HSCT. The first patient was a 31-year-old woman who relapsed after auto-HSCT. Subsequently, HLA-matched allo-HSCT was considered as a salvage treatment. Modified BU/CY conditioning regimens included BU/CY/Vm26/Ara-C. Donor lymphocyte infusion was used to reduce the risk of relapse. After allo-HSCT, the tumor in her nasal cavity gradually disappeared. She has been in continuous complete remission (CR) for 3 years. The second patient was a 26-year-old woman diagnosed with stage IIIB advanced nasal NK/T-cell lymphoma who was resistant to combination radiochemotherapy. She underwent HLA-matched allo-HSCT as a salvage treatment. Modified BU/CY conditioning regimens included BU/CY/MeCCNu/Ara-C. She has been in continuous CR for five years. The stem cell source was peripheral blood for both patients, and there was no severe graft-versus-host disease in either patient. Our clinical experience suggests that allo-HSCT with a modified conditioning regimen is a promising treatment for patients with relapsed or refractory nasal NK/T-cell lymphoma.

A typical mechanical character of rock is that the tensile strength is far less than the compressive strength. Meanwhile, the test data of tensile strength is very dispersive. Because the direct tensile tests always result in failure due to the difficulty in clamping the rock sample, the splitting test is used to determine the tensile strength of rock. There are four kinds of loading modes in the splitting test in actual laboratory test: angle pad splitting, round pad splitting, aclinic loading platen splitting, arc loading platen splitting. In this paper, the direct tensile test, the splitting test and the influence of different loading modes on rock tensile strength were studied. In order to study the stress distribution, the progressive splitting failure process was numerically modeled under the four kinds of loading cases by the Realistic Failure Process Analysis code (RFPA2D). Results show that the stress states under angle pad splitting, round pad splitting are similar to the stress states under diametrical compressive state. Regarding that the round pad splitting test is easy to implement, and its numerical results are also stable relatively, the round pad loading mode was suggested to be adopted.

The periodically distributed fracture spacing phenomenon exists in the failure process of the reinforced concrete prism under uniaxial tension. In this paper, A numerical code RFPA3D (3D Realistic Failure Process Analysis) is used to simulate the three-dimensional failure process of plain concrete prism specimen and reinforced concrete prism specimen under uniaxial tension. The reinforced concrete is represented by a set of elements with same size and different mechanical properties. They are uniform cubic elements and their mechanical properties, including elastic modulus and peak strength, are distributed through the specimens according to a certain statistical distribution. The elastic modulus and other mechanical properties are weakened gradually when the stresses in the elements meet the specific failure criterion. The displacement-controlled loading scheme is used to simulate the complete failure process of reinforced concrete. The analyses focus on the failure mechanisms of the concrete and reinforcement. The complete process of the fracture for the plain concrete prism and the fracture initiation, infilling and saturation of the reinforced concrete prism is reproduced. It agrees well with the theoretical analysis. Through 3D numerical tests for the specimen, it can be investigated the interaction between the reinforcement and concrete mechanical properties in meso-level and the numerical code is proved to be an effective way to help thoroughly understand the rule of the reinforcement and concrete and also help the design of the structural concrete components and systems.

Reinforced concrete structures are generally designed to allow cracking under service loading. Accurate modeling of crack formation and propagation at lower load levels is therefore important. In this paper, a Material Failure Process Analysis code (MFPA2D) is used to model the crack initiation and propagation in reinforced concrete bridge pier subjected to eccentric loading. In our numerical model, the reinforced concrete is assumed to be a three-phase composite composed of concrete, reinforcement and interfaces between them. Numerically obtained results of cracking loads and global load-displacement response agree well with experimentally measured values. It has been found that the fracture of the concrete observed at the macroscopic level is predominated by tensile damage at the mesoscopic level.

This short paper will present a two-dimensional (2D) model of masonry material. This mesoscopic mechanical model is suitable to simulate the behavior of masonry. Considering the heterogeneity of masonry material, based on the damage mechanics and elastic-brittle theory, the new developed Material Failure Process Analysis (MFPA2D) system was brought out to simulate the cracking process of masonry, which was considered as a three-phase composite of the block phase, the mortar phase and the block-mortar interfaces. The crack propagation processes simulated with this model shows good agreement with those of experimental observations. It has been found that the shear fracture of masonry observed at the macroscopic level is predominantly caused by tensile damage at the mesoscopic level. Some brittle materials are so weak in tension relative to shear that tensile rather than shear fractures are generated in pure shear loading.

An integrated vehicle collision-avoiding radar and intelligent cruise control system is proposed. Collision-avoiding radar measures the distance of a vehicle-to-vehicle and roadblocks automatically, and then Cruise Control System design optimal acceleration for the vehicle-to-vehicle distance control. An integrated radar and intelligent cruise control law has been proposed. Using this control law, the brake controller forces the vehicle acceleration to converge to the desired acceleration. It has been shown via the simulations with good distance control performance in both high speed and low speed stop and good driving situations. Vehicle Collision-avoiding Radar System and Intelligent Cruise Control System have very important significance on improving vehicle active safety and reducing driver’s fatigue. Collision-avoiding Radar System and Intelligent Cruise Control System will be the necessary equipment in future vehicle.

Masonry structure is heterogeneous and has been widely used in building and construction engineering. The study on cracking pattern of masonry structure is significant to engineering design. Many previous investigations on the failure process of masonry structure are usually based on the homogenization technique by selecting a typical unit of masonry to serve as a representative volume. This kind of numerical analysis neglects the mesoscopic heterogeneous structure, which cannot capture the full cracking process of masonry structures. The cracking process of masonry structure is dominantly affected by its heterogeneous internal structures. In this paper, a mesoscopic mechanical model of masonry material is developed to simulate the behavior of masonry structure. Considering the heterogeneity of masonry material, based on the damage mechanics and elastic-brittle theory, the new developed Material Failure Process Analysis (MFPA2D) system was put forward to simulate the cracking process of masonry structure, which was considered as a two-phase composite of block and mortar phases. The crack propagation processes simulated with this model shows good agreement with those of experimental observations. The numerical results show that numerical analysis clearly reflect the modification, transference and their interaction of the stress field and damage evolution process which are difficult to achieve by physical experiments. It provides a new method to research the forecast theory of failure and seismicity of masonry. It has been found that the fracture of masonry observed at the macroscopic level is predominantly caused by tensile damage at the mesoscopic level.

Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem cell transplantation from unrelated donor due to its ability to prevent acute and chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA-mismatched allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n = 28) had similar baseline demographic, disease, and transplant characteristics. There were no significant between-groups differences in the probability of acute GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with nonsignificant trends toward higher disease-free survival at 3-year follow-up compared with ATG-T (45.7 ± 11.1 vs 61.3 ± 9.7 %, respectively, P = 0.07). A significantly greater proportion of ATG-T patients experienced high fever than ATG-F patients (P

The purpose of this study was to describe nurse burnout, job satisfaction, and intention to leave and to explore the relationship of work environment to nursing outcomes in a sample of 9,698 nurses from 181 hospitals in China. Nurses reported moderate levels of emotional exhaustion and depersonalization and high levels of reduced personal accomplishment. Nearly one-fifth of the nurses reported high levels of burnout on all three dimensions. Forty-five percent of the nurses were dissatisfied with their current job; these nurses were most dissatisfied with their salary. Five percent of nurses reported an intention to leave. Nurses reporting mixed and good work environments were less likely to report high burnout, job dissatisfaction, and intention to leave compared with those in poor work environments. The results suggest that high burnout and low job satisfaction are prominent problems for Chinese nurses, and improving work environment might be an effective strategy for better nursing outcomes in Chinese hospitals.

Objective: In this study, to investigate clinical characteristics, response, outcome, and prognosis of peripheral blood stem cell transplantation (PBSCT) for patients with peripheral T-cell lymphoma (PTCL). Methods: This study retrospectively analyzed the efficacy of PBSCT in 38 patients with PTCL. Kaplan–Meier methods were used in survival analysis, and the Cox regression model was applied in multivariate analysis. There were ten clinical parameters were analyzed. Results: The 2-year overall survival (OS) was 46%, and the 5-year OS was 34% after a median follow-up of 40 months. The patients who received allogeneic PBSCT (allo-PBSCT) had a higher nonrelapse mortality than autologous PBSCT (auto-PBSCT), but they could achieve a longer-term disease-free survival in the former, which OS could achieve 40%. Survival analysis with Kaplan–Meier method showed the pretransplant disease status, B symptoms, serum lactate dehydrogenase (LDH) in early (>275 U/L), Eastern Cooperative Oncology Group (ECOG) score (>1), prognostic index for PTCL score (>2) were all prognostic factors for posttransplant OS. Pretransplant disease status is the only prognostic factor for allo-PBSCT. Conclusion: The key was to reducing transplant-related mortality of allo-PBSCT by reduced-intensity conditioning. Factors such as level of early serum LDH, extranodal involvement, B symptoms, ECOG score, Ann Arbor stage, and pretransplant disease status were all related to the prognosis of patients treated with PBSCT. Allo-PBSCT maybe suggested as the first line therapy for late-stage PTCL patients who could reach treatment remission before transplantation.

The most effective post-first CR1 treatment for patients with AML, allogenic hematopoietic SCT (allo-HSCT) or autologous hematopoietic SCT (HSCT), remains to be conclusively determined. This study aimed to compare the effectiveness of treatment with allo-HSCT or auto-HSCT in patients with AML after CR1. We retrospectively reviewed medical records of 127 patients with AML who received allo- (n=52) or auto-HSCT (n=75) after achieving CR1 at a single medical center. The disease-free and overall survival rates and complications were analyzed. During a median follow-up of 1215 days, all patients (100%) in allo-HSCT group and 94.7% of patients in the auto-HSCT group had successful outcomes. The disease-free survival rates were 65.3% and 50.6% for allo- and auto-HSCT groups, respectively (P=0.158), while the overall survival rates were 65.3% and 54.9%, respectively (P=0.486). The recurrence rate was higher with auto-HSCT, whereas the GVHD only happened with allo-HSCT. In conclusion, auto-HSCT was as effective as allo-HSCT for the treatment of patients with AML after CR1. This is encouraging given that allo-HSCT is not always feasible in China because of a lack of matching donors.

Background Colon cancer is one of the most aggressive human malignancies, with a very poor prognosis. Although it has been suggested that different isoforms of the lymphoid enhancer factor (LEF-1) have opposing biological activities, the biological outcome of aberrant LEF-1 activation in colon cancer is still unclear. The aim of this study was to evaluate the effect of the different LEF-1 phenotypes on the growth of colon carcinoma cell lines. A deeper understanding of these processes might improve the targeted therapies for colon cancer by regulating the expression of LEF-1. Methods The role of different isoforms of LEF-1 on the growth of human colon carcinoma cell lines (SW480 and HT-29) was studied using various in vitro and in vivo assays. In vitro proliferation, migration, adhesion and apoptosis of the cells stably transfected of different isoforms of LEF-1 were monitored by MTT assay, carboxyfluorescein diacetate–succinimidyl ester staining, annexin V staining, ECM adhesion assay and transwell assay, respectively. In nude mice, the formation of neovasculature in the tumors formed by our constructed cells was measured by immunohistochemistry. All the data were analyzed using a t test, and data were treated as significant when p Results Overexpression of truncated LEF-1 (LEF-1-ΔL) in the colon cell lines, SW480 and HT29, inhibited their growth significantly in vitro and in vivo, but the full-length LEF-1 (LEF-1-FL) promoted the proliferation of HT29. Inactivation of Wnt signaling by LEF-1-ΔL reduced the expression of CXCR4 in colon cell lines, which may lead to a decrease in activities such as migration, adhesion and survival. In nude mice, the formation of neovasculature as well as an increase in tumor volume were inhibited by the short isoform of LEF-1. LEF-1-FL, however, caused an increase in all these parameters compared with controls. Conclusions These findings suggest that LEF-1 might play an important role in colon carcinogenesis by acting as a regulator. Enhanced expression of LEF-1-FL, which occurs frequently in colon cancer, may be a new target for clinical therapy.

The CXCR4 and Nrf2 signaling pathways are abnormally activated in response to cellular stress in various types of human cancers. In this study, we examined the expression of CXCR4 and Nrf2 in colorectal cancer (CRC) tissue specimens and investigated their correlation with patient clinicopathologic characteristics. We determined CXCR4 and Nrf2 expression in 76 CRC tissue specimens and paired normal tissue specimens by immunohistochemistry and real-time PCR. We found that the protein and mRNA transcript levels of CXCR4 were significantly higher in CRC tissue specimens than in paired normal tissues, while the expressions of Nrf2 protein and mRNA were increased in CRC tissues compared to distant non-cancerous tissues. High expression level of CXCR4 was positively correlated with poorly differentiated (P = 0.031), more advanced tumor-node-metastasis (TNM) stage (P = 0.019), lymph node metastasis (P = 0.007) and distant metastasis (P = 0.018). However, the expression of Nrf2 protein was positively correlated with larger tumor size (P = 0.049), more advanced TNM stage (P = 0.013), lymph node metastasis (P = 0.016) and distant metastasis (P = 0.023). Moreover, there was a strong relationship between CXCR4 and Nrf2 expression in CRC tissues, indicating that high Nrf2 expression may contribute to CXCR4 overexpression. In addition, combined expression of CXCR4 and Nrf2 strongly correlated with lymph node metastasis and distant metastasis (P = 0.003). Furthermore, we found that combined high expression of CXCR4 and Nrf2 had stronger correlation with lymph node metastasis and distant metastasis than any single molecule did. This study indicated that the abnormal expression of CXCR4 and Nrf2 contributed to the progression of CRC.

We present the status of the Tau/charm factory design study in China. The report consists of a detailed description of the different phases of the study and the local organization established to carry it out. A list of workshops intended to regularly review the status of the design study is included.

4556 Objective: To investigatethe clinical features and prognostic factors, compare the treatment efficiency of chemotherapy and hematopoietic stem celltransplantation (HSCT) in Chinese patients with lymphoblastic lymphoma (LBL). Methods: We retrospectively analyzed clinical features, outcomes and prognosis of fifty-two patients with LBL who underwent chemotherapy (n=31) or HSCT (n=21) from January 1998 to December 2010 in our hospital. Results: The median age was 19.5years (12–75 years). There was a male predominance with a ratio of 2.7:1. At presentation, 76.9% were T-cell immunophenotype, 90.4% were Ann Arbor stage III/‡W, 71.2% had mediastinal tumor, 30.8% presented with bone marrow involvement, and 7.7% had central nervous system (CNS) disease. Of the 52 patients, the overall response rate (ORR) was 90.4% and complete remission (CR) rate was 75.0%. The ORR rates in patients treated with ALL-like regimens and those treated with NHL-like regimens were 94.7% and 78.6%(P=0.221), CR rates were 81.6% and 57.2%(P=0.149), respectively. With a median follow-up of 19 months, the overall survival (OS) for all patients was 41.5% at two years and 29.0% at five years, and progression-free survival (PFS) was 33.2% and 25.3%, respectively. The 5-year OS rate was53.6% for the HSCT group and 12.1% for the chemotherapy group (P=0.001). For transplanted patients, 5-year PFS rate for patients who were in CR1 or not in CR1 before transplantation were 65.5% and 33.3%, respectively (P=0.036). Multivariate analyses showed that immunophenotype, lactatedehydrogenase (LDH), response to induction therapy and transplantation were independent prognostic factors (P Conclusion: LBL is more common in young men and most patients had advanced diease at diagnosis. Clinically, it often presents with mediastinal, bone marrow and CNS involvement. More intensive ALL-like regimens appear superior to NHL-like regimens. Compared with chemotherapy, HSCT may improve overall survival. The use of HSCT in CR1 produces a trend for improved PFS. T-cell immunophenotype, elevated LDH, disease status more advanced than CR and patients without HSCT are independently associated with inferior outcomes. Disclosures: No relevant conflicts of interest to declare.