Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia

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

Expression pattern of GATA-1,-2 and-3 genes in leukemic bone marrow microenvironment

Objective： The aim of the study was to investigate the expression pattern of hematopoietic transcription factor GATA-1, -2 and -3 genes in leukemic bone marrow （BM） micreenvironment [including bone marrow stremal cells （BMSCs） and BM hematopoietic cells]. Methods： Mononuclear cells were isolated from BM of patients with acute myeloid leukemia （AML）, chronic myelogenous leukemia （CML）, or acute lymphoblasUc leukemia （ALL）. Adherent cells （BMSCs） and nonadherent ceils （BM hematopoietic cells） were collected after long-term culture in vitro. The semi-quantitative expression levels of GATA genes in the BMSCs or BM hematopoietic cells from patients with leukemia were analyzed by using RT-PCR-ELISA and com- pared with normal controls. Results： The expression level of GATA-1 gene in the BMSCs from CML group was significantly lower than that of the normal controls. The expression level of GATA-3 gene in the BMSCs from ALL was higher than that of the normal controls, but that from CML was lower than the normal controls. Dominant expression of GATA-3 gene was found in the normal BM hematopoietic cells. The dominant expression of GATA-2 gene was found in the normal BMSCs and the BMSCs from CML, whereas the dominant expression of GATA-3 gene was detected in the BMSCs from AML. Conclusion： GATA-1, -2 and -3 genes might play a role in hematopoiesis regulation in leukemia, and the changes of expression pattern of GATA genes might influence the hematopoiesis in BM microenvironment and relate to the pathogenesis and development of leukemia.

Stimulation of staphylococcal enterotoxin A combined with PML-RARα peptide on the specifical T-cells against NB4 cell line

Objective： To investigate the effects of staphyococcal enterotoxin A （SEA） on the cytotoxicity of T cells stimulated by PML-RARa peptide in vitro. Methods： Peripheral blood mononuclear cells （MNC） from healthy donor were obtained by density gradient centrifugation on Ficoll-Hypaque, MNC were cultured with PML-RARa peptide and SEA for 20 days. After induction, the cytotoxicity of T cells induced against NB4 and K562 cell lines were examined by Cell Counting Kit-8 （CCK-8）. The CD4 and CD8 surface markers on the harvested CD3^＋ T cells were detected by flow cytometry （FCM）. Results： The cytotoxicity of T cells induced by PML-RARa peptide with SEA was higher than that of T cells induced only by PML-RARa peptide against NB4 cells. The FCM assay showed that the ratio of CD4^＋/CD8^＋ T cells were gradually decreased in both groups of PML-RARα peptide whether with SEA or not at the intervals of day 5,10 and 20 day after induction, but the most significantly decreased by PML-RARe peptide with SEA. Conclusion： The specific cytotoxicity of T cells induced by PML-RARa peptide against NB4 cells could be enhanced with superantigen SEA.

Synchronization transition of a modular neural network containing subnetworks of different scales

Time delay and coupling strength are important factors that affect the synchronization of neural networks.In this study,a modular neural network containing subnetworks of different scales was constructed using the Hodgkin–Huxley(HH)neural model;i.e.,a small-scale random network was unidirectionally connected to a large-scale small-world network through chemical synapses.Time delays were found to induce multiple synchronization transitions in the network.An increase in coupling strength also promoted synchronization of the network when the time delay was an integer multiple of the firing period of a single neuron.Considering that time delays at different locations in a modular network may have different effects,we explored the influence of time delays within each subnetwork and between two subnetworks on the synchronization of modular networks.We found that when the subnetworks were well synchronized internally,an increase in the time delay within both subnetworks induced multiple synchronization transitions of their own.In addition,the synchronization state of the small-scale network affected the synchronization of the large-scale network.It was surprising to find that an increase in the time delay between the two subnetworks caused the synchronization factor of the modular network to vary periodically,but it had essentially no effect on the synchronization within the receiving subnetwork.By analyzing the phase difference between the two subnetworks,we found that the mechanism of the periodic variation of the synchronization factor of the modular network was the periodic variation of the phase difference.Finally,the generality of the results was demonstrated by investigating modular networks at different scales.

Capillary blood flow in patients with dysmenorrhea treated with acupuncture

OBJECTIVE: To observe capillary blood flow at acupoints during acupuncture treatment of primary dysmenorrhea and gain new insights into its analgesic mechanism. METHODS: Patients with primary dysmenorrhea were enrolled and randomly assigned to a treatment or control group. Subjects' symptoms were differentiated into variousTraditional Chinese Medicine(TCM) syndromes and treated for 10 sessions with puncturing acupuncture or self-pressing right-hand Hegu(LI 4), adding other acupoints based on syndrome. Laser speckle was used to compare the change in the vasomotor amplitude and perfusion of the capillaries in Hegu(LI 4) before and during the treatment. Each subject was required to finish the period pain symptoms observation form, verbal rating scales, numerical rating scale, pain rating index, face rating scale, Zung self-rating depression scale, Zung self-rating anxiety scale, and numerical rating scale before and after treatments. RESULTS: After 10 sessions, the symptom scores, pain index(PI), and visual analog scale(VAS) decreased significantly in treatment group. The volume of blood flow in Hegu(LI 4) declined slightly. No significant evidence supported that needling caused capillary contraction, but the capillary vasomotor amplitude at Hegu(LI 4) increased remarkably. CONCLUSION: Acupuncture can increase the capillary blood flow, thus promoting the flow of Qi and blood in terms of TCM theory, which facilitates pain relief.

Opportunities and challenges of using big data for global health

The past two decades have witnessed the burgeoning of enormous digital technologies and data collected via countless channels.They are combined in numerous ways in different fields,including epidemiology,mHealth and modeling of health systems,with the intention to improve human health(e.g.,clinical decision support,electronic medical record management)[1-6].However,this is a new interdisciplinary area where no single scientific discipline knows how to take full advantage of these data and technologies to solve health problems[1].

Spectral decimation for a graph-directed fractal pair

We introduce a graph-directed pair of planar self-similar sets that possess fully symmetric Laplacians. For these two fractals, due to Shima’s celebrated criterion, we point out that one admits the spectral decimation by the canonic graph approximation and the other does not. For the second fractal, we adjust to choosing a new graph approximation guided by the directed graph, which still admits spectral decimation. Then we make a full description of the Dirichlet and Neumann eigenvalues and eigenfunctions of both of these two fractals.