Continuous-variable quantum key distribution coexisting with classical signals on few-mode fiber.

Continuous-variable quantum key distribution (CVQKD) holds an advantage of well compatibility with classical coherent optical communications. However, there exists a performance trade-off between CVQKD and classical communication on single-mode fiber (SMF) because of the spontaneous Raman scattering. Space-division multiplexing (SDM) technique may provide a feasible way to mitigate this performance trade-off in short-distance communication while CVQKD coexisting with classical signals on few-mode fiber (FMF). Here, we examine the feasibility of CVQKD coexisting with classical signals on FMF and analyze the noise impact in weak coupling regime. We find that the inter-mode crosstalk generated from the mode coupling and re-coupling between modes and the group delay spread originated from the differential group delay (DGD) contribute the main noise sources. DGD may become one of the main limits for FMF-based CVQKD towards high-speed system. In addition, a well channel wavelength management is needed to suppress the inter-mode four-wave-mixing for achieving the positive secret key rates. The numerical simulations identify the key parameters for CVQKD system, enabling a helpful insight for realizing security analysis of the Gaussian modulated coherent state protocol. It shows that CVQKD coexisting with high power classical signals on FMF is feasible to implement with standard telecommunication components and able to operate at higher secret key rates. The results may provide a potential guideline for the practical high-rate CVQKD integrating with the FMF-based configuration.

Improving Underwater Continuous-Variable Measurement-Device-Independent Quantum Key Distribution via Zero-Photon Catalysis.

Underwater quantumkey distribution (QKD) is tough but important formodern underwater communications in an insecure environment. It can guarantee secure underwater communication between submarines and enhance safety for critical network nodes. To enhance the performance of continuous-variable quantumkey distribution (CVQKD) underwater in terms ofmaximal transmission distance and secret key rate as well, we adopt measurement-device-independent (MDI) quantum key distribution with the zero-photon catalysis (ZPC) performed at the emitter of one side, which is the ZPC-based MDI-CVQKD. Numerical simulation shows that the ZPC-involved scheme, which is a Gaussian operation in essence, works better than the single photon subtraction (SPS)-involved scheme in the extreme asymmetric case. We find that the transmission of the ZPC-involved scheme is longer than that of the SPS-involved scheme. In addition, we consider the effects of temperature, salinity and solar elevation angle on the system performance in pure seawater. The maximal transmission distance decreases with the increase of temperature and the decrease of sunlight elevation angle, while it changes little over a broad range of salinity.

Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses.

Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and α-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.

Aberrant phosphorylation of signal transducer and activator of transcription 3 protein of the CD4+ T cells in patients with primary immune thrombocytopenia.

: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count of which dysfunctional cellular immunity in its pathogenesis. Signal transducer and activator of transcription 3 (STAT3) is critical for the differentiation of T cells. The present study was aimed to investigate the STAT3 protein phosphorylation of CD4 T cells in ITP patients. Fourteen patients of newly diagnosed ITP with complete remission (R group) and other 15 newly diagnosed ITP patients with nonresponse (N group) after corticosteroids therapy were included. Sixteen healthy human volunteers were served as normal controls (C group). Blood samples were collected before and after the therapy. Serum levels of IL-6 were measured by ELISA. The phosphorylation of STAT3 protein (pSTAT3) and the percentage of Th17 cells of the CD4 T cells were analyzed by flow cytometry. The STAT3 mRNA expression was examined by Real-time PCR. The level of IL-6 in the R group was higher than that in the C group (P = 0.02) whereas no difference was found between groups of N and C. The basal level of pSTAT3 in the R group was significantly higher when compared with N group (P = 0.002). The percentage of Th17 cells of the CD4 T cells in the ITP patients was numerically higher than that in the controls (P = 0.03). Our results indicate that ITP patient with higher basal level of pSTAT3 might have more favorite response to the corticosteroid therapy, which warrants further investigation on the prognostic role of pSTAT3 in ITP.

The expression profile of toll-like receptor signaling molecules in CD19(+) B cells from patients with primary immune thrombocytopenia.

BACKGROUND: B cells play a critical role in the pathogenesis of immune thrombocytopenia (ITP), and toll-like receptor (TLR) signaling is essential for the activation of autoreactive B cells. The objective of this study was to investigate the expression profile of TLR signaling molecules in circulating and splenic CD19(+) B cells isolated from ITP patients. METHODS: CD19(+) B cells were magnetically isolated from peripheral blood and splenocytes. Human Toll-Like Receptor Signaling Pathway RT(2) Profiler™ PCR Array was used to determine the differences in mRNA expression of 84 TLR signaling pathway genes between ITP patients and controls. Flow cytometry was used to investigate intracellular expression of cytokines (IL-1ß and IL-10). RESULTS: A total of 31 genes involving TLR signaling pathways were differentially transcribed in circulating CD19(+) B cells, among which 27 were up-regulated in ITP. By comparison, differentially transcribed genes amounted to 39 in splenic B cells in ITP, among which only two were down-regulated. Up to 18 TLR signaling molecules exhibited up-regulated transcriptional levels both in splenic B cells and in circulating B cells in ITP. However, Only IL-10 and IL-1ß were significantly upregulated in both the circulating and splenic B cells of patients with ITP. Intracellular staining of IL-10 and IL-1ß confirmed the results of PCR Array. CONCLUSIONS: The expression of TLRs and downstream cytokines, including IL-10 and IL-1ß, is up-regulated in circulating and splenic B cells in ITP patients, suggesting that activated TLR signaling pathways in B cells may play dual roles in the pathophysiology of primary ITP.

CXCL13, CCL4, and sTNFR as circulating inflammatory cytokine markers in primary and SLE-related autoimmune hemolytic anemia.

BACKGROUND: A considerable proportion of autoimmune hemolytic anemia (AIHA) are secondary to underlying autoimmune disorders, especially syetemic lupus erythematosus (SLE), and the clinical and laboratory index for early discrimination between primary and SLE-related AIHA has yet to be defined. In the present study, we proposed novel cytokine patterns in the pathogenesis of AIHA as well as parameters for the timely identification of SLE-related patients. METHODS: AIHA patients confirmed by immunohematology techniques from September 2010 to December 2012 in our facility were consecutively included and categorized into primary (n = 19) and SLE-related (n = 18) groups. Plasma cytokine profiles were measured in a single procedure by Quantibody Human Inflammatory Array 1 (RayBiotech, Norcross, GA). RESULTS: SLE-related AIHA patients demonstrated younger age (39 ± 20 vs.57 ± 16 years, p = 0.004), poorer reticulocyte compensation (6.8 ± 7.1 vs.12.2 ± 8.6%, p = 0.045), lower levels of lactate dehydrogenase [361 (265-498) vs. 622 (387-1154) U/L, p = 0.004], and higher occurrence of anticardiolipin antibody [9/18 (50%) vs. 2/19 (10.9%), p = 0.009]. MCP-1/CCL2, MIP-1ß/CCL4, BLC/CXCL13, IL-8/CXCL8, sTNFRI, and sTNFRII were significantly up-regulated in both groups, while sTNFRII was remarkably higher in SLE-related patients. Among both groups, hemoglobin level was negatively correlated with CXCL13 (r = -0.332, p = 0.044), while reticulocyte count was positively correlated with CCL4 (r = 0.456, p = 0.005). CONCLUSION: CXCL13 and CCL4 could act as circulating biomarkers in AIHA, and indicated disease severity and erythroid compensation, respectively. Higher plasma sTNFRII might favor the diagnosis of SLE-related instead of primary AIHA.

Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients.

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder. Excessive activated CD4(+) T effector cells (Teffs) and compromised regulatory T cells (Tregs) were reported in ITP patients, yet little is known about the mechanisms. Interleukin-10 (IL-10) is an important regulatory cytokine of Tregs in inflammatory condition. It has been recently highlighted that IL-10-producing Tregs contribute to the effective controls of several autoimmune diseases. Hence this study was aimed to examine the role of IL-10 produced by Tregs in newly diagnosed ITP patients. Newly diagnosed ITP patients and healthy volunteers were enrolled to assess the numbers of peripheral Th1, Th17 cells and Tregs. CD4(+)CD25(-)Teffs and CD4(+)CD25(+)Tregs were purified. CD4(+)CD25(-)Teffs, labeled with CFSE, were cultured alone or with Tregs for 5 days, and the supernatants were then collected for IL-10 concentration test. The role of IL-10 in Tregs' inhibitory function was also determined. In ITP patients, Teffs were excessively activated, while the Tregs were numerically and functionally impaired. The percentages of IL-10(+) Tregs in Tregs' population were found elevated dramatically in ITP patients but decreased in the remitted patients. The IL-10 concentrations in the cultured supernatant were decreased in ITP patients but elevated in the remitted patients. Furthermore, the IL-10 secretion by Tregs was dramatically decreased in ITP patients. IL-10 treatment enhanced the suppression effect of Tregs toward Teffs, whereas anti-IL-10 treatment boosted the proliferation of Teffs and Th17 cells. Excessive activated Teffs and impaired Tregs play major roles in the exuberant CD4(+) T cells immune responses of ITP. The inhibitory effect of Tregs toward Teffs is largely exerted by IL-10. Insufficient secretion of IL-10 compromises the inhibitory capability of Tregs against Teffs in newly diagnosed ITP patients.

Retrospective comparison of fludarabine in combination with intermediate-dose cytarabine versus high-dose cytarabine as consolidation therapies for acute myeloid leukemia.

This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission. Disease-free survival (DFS) and overall survival (OS) based on age (≥ 60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013. Total 82 patients (FA, n = 45; HiDAC, n = 37; 14-65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥ 60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients.

Aberrant frequency of IL-10-producing B cells and its association with Treg/Th17 in adult primary immune thrombocytopenia patients.

BACKGROUND: Regulatory B cells (Breg) are a distinct B cell subset with immunoregulatory properties. Pivotal to Breg function is interleukin-10. This study was to investigate the role of IL-10-producing B cell (B10) and its association with Treg and Th17 subsets in immune thrombocytopenia (ITP) patients. METHODS: Peripheral blood mononuclear cells from ITP patients and controls were stimulated with PMA, ionomycin, and Brefeldin A. The frequencies of CD19(+)IL-10(+) B cells, CD3(+)CD4(+)IL-17(+) Th17 cells, and CD4(+)CD25(hi)Foxp3(+) Treg cells were analyzed by flow cytometry. The mRNA expression of Foxp3 and RORγt was detected by real-time quantitative PCR. RESULTS: The number of B10 cells was elevated in ITP patients. After first-line therapies, it remained at high level in patients who achieved complete or partial response but decreased in those who acquired no response. There was a positive correlation between B10 cells and Tregs in ITP both before and after therapies. The ratio of Treg/Th17 decreased in ITP, and it strongly correlated with B10 cells. CONCLUSIONS: The frequency of B10 cells is elevated in ITP and it correlates with both the Tregs counts and the Treg/Th17 ratio. B10 cells to regulate functional T cell subsets might be impaired in patients with ITP.

Abnormal platelet kinetics are detected before the occurrence of thrombocytopaenia in HBV-related liver disease.

BACKGROUND & AIMS: Thrombocytopaenia is a frequent feature in patients with HBV-related liver disease. Its underlying mechanism is not fully understood. Multiple factors might contribute to the development of thrombocytopaenia. In this study, we investigated the reticulated platelets (RP), glycocalicin (GC), serum thrombopoietin (TPO) and platelet glycoprotein (GP) in different stages of the disease. METHODS: One hundred and fourteen patients with HBV-related liver disease (30 with chronic hepatitis B (CHB), 20 patients in Child A without thrombocytopaenia, 19 patients in Child A with thrombocytopaenia, 45 in Child B/C with thrombocytopaenia) and 25 normal controls (NC) were enrolled. Liver cirrhosis (LC) was classified according to modified Child-Turcotte-Pugh (CTP) score. Serum TPO levels and GC were measured by ELISA. RP and platelet glycoprotein (GP) expression were detected by flow cytometry. RESULTS: The TPO levels of patients with LC were significantly lower than that of controls, even in patients of Child A without thrombocytopaenia group. Serum TPO level was positively correlated (r = 0.65, p < 0.01) with serum albumin in Child B/C group. Both the RP percentages and the glycocalicin index (GCI) levels were significantly higher in patients groups including CHB and Child A without thrombocytopaenia than that of normal controls. A negative correlation existed in HBV DNA copies and the GPs% in patients with CHB and Child A without thrombocytopaenia. CONCLUSION: Abnormal platelet production, destruction and platelet-specific glycoproteins levels were detected before the occurrence of thrombocytopaenia in HBV-related liver disease, indicating that multiple mechanisms might play roles in thrombocytopaenia in HBV-infected patients.

High-dose dexamethasone modulates serum cytokine profile in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder which is characterized by decreased platelet count. Serum cytokines play an important role in the pathogenesis of ITP by initiating and perpetuating various cellular and humoral autoimmune processes. To investigate a broad spectrum of cytokines in ITP patients and the effects of high-dose dexamethasone (HD-DXM) regimen on serum cytokines profile, a multiplex cytokine assay was used to measure the serum levels of 20 circulating cytokines simultaneously in 22 patients before and after oral administration of 40mg/day DXM for 4 consecutive days. A cohort of 10 healthy individuals was served as control. Serum levels of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, growth-related oncogene (GRO), interferen (IFN)-γ and tumor necrosis factor (TNF)-α were significantly decreased in pre-treatment patients, compared with healthy controls (p<0.05). After HD-DXM treatment, IL-4, IL-5, IL-6, IL-12p70, IL-13, GRO, IFN-γ and TNF-α were significantly increased in remission patients as compared with patients before treatment (p<0.05). However, there was no significant difference (except TNF-α) between remission patients and healthy controls (p>0.05). All these cytokines decreased again in relapse patients. Our findings suggest that measuring cytokine levels might help in the clinical assessment of ITP, and the HD-DXM therapy could correct the derangement of serum cytokines.

HBsAg is an independent prognostic factor in diffuse large B cell lymphoma patients in rituximab era: result from a multicenter retrospective analysis in China.

This study mainly focused on the impact of Hepatitis B virus (HBV) infection on the prognosis of diffuse large B cell lymphoma (DLBCL) patients in rituximab era, using a Cox regression model to ascertain the prediction value of the serum HBV marker in survivals. Three hundred and eighty four DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin/epirubicin, vincristine and prednisone (R-CHOP-like regimens) or CHOP-like regimens were included. Progression-free survival (PFS) and overall survival (OS) of the patients have or have not received rituximab were analyzed separately. In the CHOP group, HBV infection has not been found a profound impact on the survivals. In the R-CHOP group, PFS and OS were inferior in HBsAg-positive patients (p=0.031 and p=0.006, respectively); after adjusting for International Prognostic Index parameters, HBsAg is an independent unfavorable factor for both PFS (RR=2.492) and OS (RR=2.589).

[A clinical comparative study on treatment of severe newly diagnosed immune thrombocytopenia by recombinant human thrombopoietin combined with glucocorticoid].

OBJECTIVE: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of severe newly diagnosed primary immune thrombocytopenia (ITP). METHODS: From June 2009 to December 2012, 24 male patients and 38 female patients with the diagnosis of severe primary ITP in our hospital were randomized into trial group (31 cases) or control group (31 cases), the median age was 50 years (range: 21-84 years). Trial group was treated with rhTPO combined with glucocorticoid, and control group was treated with glucocorticoid only. RESULTS: At the day 3, 7 and 14 from the beginning of treatment, the average platelet count (APC) in trial group[(35.5±24.9)×109/L, (135.2±94.9)×109/L and (192.0±109.1)×109/L]were significantly higher than that in control group[(24.5±15.6)×109/L, (78.2±121.9)×109/L and (95.8±60.5)×109/L, P=0.022, 0.009 and 0.001, respectively]. There was no significant difference in APC between the two groups at day 28 and 90 after treatment[(147.8±59.1)×109/L vs (105.1±56.9)×109/L, P=0.243; (137.4±52.3)×109/L vs (104.3±59.8)×109/L, P=0.568, respectively]. At the day 7, 14 and 28, the complete response rates in trial group were 61.3%, 87.1% and 80.6%, which were also significantly higher than that in control group (16.1%, 29.0% and 48.3%, P=0.000, 0.000 and 0.004, respectively). The median time to response in trial group was 3 days while in the control group was 5 days; the median duration of complete response in trial group was 76 days while in the control group was 54 days. In trial group, there were 4 cases treated with platelet transfusion, while in control group there were 11 cases, respectively. CONCLUSION: For patients with severe primary ITP, rhTPO combined with glucocorticoid could rapidly increase the platelet count, significantly improve the complete response rate and prolonged the effect with a low incidence of tolerable adverse events compared to single use of glucocorticoid. rhTPO combined with glucocorticoid could be a new therapeutic choice to those patients.

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy.

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086-7.090, p = 0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727-6.661, p = 0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379-1.472, p = 0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544-1.956, p = 0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.

The ratio of Treg/Th17 cells correlates with the disease activity of primary immune thrombocytopenia.

BACKGROUND: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. Regulatory T (Treg) cells and T helper type 17 (Th17) cells are two subtypes of CD4(+) T helper (Th) cells. They play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 has been demonstrated in several autoimmune diseases. In this study, we aimed to investigate the ratio of the number of Treg cells to the number of Th17 cells in ITP patients and evaluate the clinical implications of the alterations in this ratio. METHODS: Thirty adult patients with newly diagnosed ITP enrolled in this study. Twelve patients had been clinically followed up for 12 months. The percentages of CD4(+)CD25(hi)Foxp3(+) Treg cells and CD3(+)CD4(+)IL-17-producing Th17 cells in these patients and healthy controls (n = 17) were longitudinally analyzed by flow cytometry. RESULTS: The percentage of Treg cells in ITP patients was significantly lower than that of healthy controls, and the percentage of Th17 cells increased significantly at disease onset. The ratio of Treg/Th17 correlated with the disease activity. CONCLUSION: The ratio of Treg/Th17 might be relevant to the clinical diversity of ITP patients, and this Treg/Th17 ratio might have prognostic role in ITP patients.

Reassessment of the prognostic value of the International Prognostic Index and the revised International Prognostic Index in patients with diffuse large B-cell lymphoma: A multicentre study.

The International Prognostic Index (IPI) is a widely accepted model that is used to predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who are treated using chemotherapy. However, the prognostic value of the IPI has been a focal point of debate in the immunochemotherapy era. The aim of this study was to reassess the value of the IPI and revised IPI (R-IPI) in a Chinese population. A multicentre retrospective analysis of DLBCL patients who were treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy alone or chemotherapy plus rituximab (R-CHOP-like) was performed. The prognostic values of IPI and R-IPI at the time of diagnosis with respect to overall survival (OS) and progression-free survival (PFS) were evaluated. Among the 438 patients in the study, 241 received a CHOP-like regimen and 197 patients received an R-CHOP-like regimen. Although the IPI remained predictive for the CHOP-like group, it failed to distinguish between the various prognostic categories in the R-CHOP-like group. Notably, redistribution of the IPI factors into R-IPI factors identified three discrete prognostic groups with significantly different outcomes in both the CHOP-like and R-CHOP-like groups. In the R-CHOP-like group, these three risk groups, very good, good and poor, had distinctly different 3-year PFS rates of 96, 84.3 and 67.5% (P=0.001), and 3-year OS rates of 96, 87.6 and 71.1% (P=0.003), respectively. Our study demonstrates the power of the R-IPI as a simplified and more clinically relevant predictor of disease outcome than the standard IPI in DLBCL populations in the rituximab era. Therefore, the R-IPI merits further study in a larger population-based prospective study.