A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Thrombopoietin Prevents CoCl-inducing Apoptosis of HUVEC through the PI3K/AKT Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of thrombopoietin (TPO) on chemical hypoxia-induced apoptosis of human umbilical vein endothelial cells (HUVEC), and to explore its potential mechanism.</p><p><b>METHODS</b>The experiment was divided into 4 groups. The untreated HUVECs were used as normal control group. HUVECs treated with CoCl was CoCl group, and TPO was added into the culture medium 48 h before CoCl treatment as TPO + CoCl group. The cells was treated with TPO alone as TPO group. The cell viability and apoptosis of each groups were tested by Cell Counter Kit 8 (CCK-8) assay and flow cytometry. The expression of Caspase-3 and mitochondrial membrane potential (MMP) were then determined by flow cytometry with Caspase-3-PE and JC-1. The effect of TPO in PI3K/AKT pathway was detected by using Western blot.</p><p><b>RESULTS</b>CoCl significantly inhibited the growth of HUVECs. The cell viability of HUVECs decreased gradually with enhancement of CoCl at a gradient of chemical concentrations (r= -0.997). CoCl dramatically increased apoptosis of HUVECs, whereas pre-treatment with TPO rescued cell apoptosis induced by CoCl (P<0.001). Further investigation found that TPO decreased the expression of Caspase-3 and inhibited the reduction of MMP induced by CoCl (P<0.05). TPO could increased the activation of PI3K/AKT pathway in HUVECs.</p><p><b>CONCLUSION</b>TPO has a protective effect against CoCl-induced apoptosis of HUVECs through activating the PI3K/AKT pathway, thus decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.</p>

PDGF-BB Promotes CFU-GM and CFU-MK Formation and Its Possible Mechnism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of platelet-derived growth factor (PDGF-BB) on the formation of granulocyte-monocyte colony forming unit (CFU-GM) and megakaryocyte colony forming unit (CFU-MK) and its anti-apoptotic effect on CHRF cells.</p><p><b>METHODS</b>The CFU-GM and CFU-MK of murine and human bone marrow cells were cultured in vitro by using plasma clot culture system. The anti-apoptotic effect of PDGF-BB on CHRF cells and its mechanism were clarified by flow cytometry.</p><p><b>RESULTS</b>PDGF-BB 0-100 ng/ml stimulated the proliferation of murine and human CFU-GM and CFU-MK in a dose-dependent manner. The maximal stimulation effect was obtained at 50 ng/ml of PDGF-BB (P<0.01). Furthermore, PDGF-BB had an anti-apoptotic effect on CHRF cells as shown by the flow cytometry with AnnexinV/PI double staining, Caspase-3 expression and JC-1 detection (P<0.05).</p><p><b>CONCLUSION</b>PDGF-BB significantly stimulates the proliferation of CFU-GM and CFU-MK in vitro, and has an anti-apoptotic effect on CHRF cells.</p>

Role of PDGF/PDGFR Pathway in Essential Thrombocythemia and Its Action Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the role of PDGF/PDGFR in essential thrombocythemia (ET) by investigating the expression of PDGF-BB in bone marrow and the expression of PDGFR-β in bone marrow cells of patients with ET and explore the new target for treating ET patients through inhibiting the PDGFR of megakaryocytes.</p><p><b>METHODS</b>The expression level of PDGF-BB in bone marrow of ET patients and normal controls were assayed by using ELISA, the expression level of PDGFR-β (CD140) in bone marrow of ET patients and normal controls were detected by using flow cytometry, the effect of PDGF-BB in JAK2/STAT3 and PI3K/AKT pathway was detected by using flow cytometry or Werstern blot, and the effect of imatinib on the megakaryopoiesis of PDGF was observed.</p><p><b>RESULTS</b>The expression level of PDGF-BB in bone marrow of ET patients was significantly higher than that in normal controls; the expression level of PDGFR-β in bone marrow of ET patients was significantly higher than that in nornal controls; PDGF-BB could activate JAK2/STAT3 and PI3K/AKT pathway of megakaryocytes, while the imatinib could block the effect of PDGF-BB on megakaryocyte.</p><p><b>CONCLUSION</b>The elevated PDGF-BB and PDGFR-β may be involved in ET, and the physiopathologic mechanism is that the elevated PDGF-BB activates PDGFR with subsequent activation of the JAK2/STAT3 and PI3K/AKT pathways, stimulating megakaryopoiesis. Imatinib may have a therapeutical effect on ET via blocking of PDGFR.</p>

Research and Application of iPS Cells in Blood System / 中国实验血液学杂志

Induced pluripotent stem cells (iPS cells) were first constructed by Takahshi and et al in 2006. They converted the mouse fibroblasts into ES-like cells via viral transduction with four transcription factors (Oct4, Sox2, Klf4 and c-Myc). Since, the significant progress has been made and many researchers have succeeded in inducing iPS cells from other human somatic cells by some novel approaches, such as combining transcriptional factors and small chemicals. IPS cells have significant prospect in clinical application. IPS cells derived from patient somatic cells can be used as a model in studying the pathogenesis of genetic hematological disease and applied in therapeutic screenings. Recent studies suggested that iPS cells can differentiate into red blood cells and platelets in vitro, which may make up a big blood bank for transfusion in future. In this review, current understanding of both recombinant technology of iPS cells and the research progress in hematology are summarized.

Effect of monoamine neurotransmitter on megakaryocytopoiesis and platelet functions / 中国实验血液学杂志

The nervous system directly regulates immunity through neurotransmitter receptors expressed on immune cells to participate in host defense and body reparation. Expression of neurotransmitter receptors on blood cells provides important evidence for a direct functional link between the nervous and hematopoietic systems. Our previous studies showed that 5-hydroxytryptamine, as a monoamine neurotransmitter, plays an important role in regulating megakaryocytopoiesis. This review summarizes recent findings of the effect of monoamine neurotransmitter on megakaryocytopoiesis and platelet function, focusing on the receptor expression on hematopoietic stem cells, megakaryocytes/platelets and their functions in order to explore the intrinsic relation of nervous system and hematopoietic system. Based on the existing research results, we find that the monoamine neurotransmitter participates in regulation of megakaryocytopoiesis, and affects on aggregation and functions activation of platelets. Moreover, it has a close link with the specific regulatory factor of megakaryocytopoiesis-TPO. Thus those results also support the "brain-bone marrow-blood-axis" viewpoint of some researchers. At present, the study of the nervous system regulating hematopoiesis is still in its infancy, the exact mechanism remains to be further studied.

Molecular mechanism of thrombopoietin signal pathways and its new effects / 中国实验血液学杂志

Thrombopoietin (TPO) is a major cytokine for megakaryocytopoiesis and thrombopoiesis, and also plays an important role in the regulation of early hematopoiesis. TPO activates a number of signal pathways to exert its biological function by binding to its receptor (c-mpl). Once these signal pathways (including Jak/STAT, PI3K/Akt, Ras/MAPK) are activated, the expression of the downstream signal molecules can be changed, which then induces biological effects. Recent researches have suggested the novel functions of TPO in many systems. The receptor of TPO (c-mpl) has been shown not only present in hematological cells, but also in many other cells and organs, such as neurons, heart muscle cells, vessel endothelial cells and so on. TPO exerts a protective effect on these cells through the interaction with c-mpl. This review discusses the molecular mechanism of TPO signal and the effect of TPO on multi-nonhematopoietic cells.

Anti-apoptotic effect of Astragalus Polysaccharide on myeloid cells / 中国实验血液学杂志

This study was aimed to assess the effect of Astragalus Polysaccharide (ASPS) on in-vitro hematopoiesis. CFU-GM assays were used to determine the effect of ASPS and thrombopoietin (TPO) on granulocytic-monocyte progenitor cells. The CFU assays were also used to investigate the effect of ASPS on the proliferation of HL-60 cells.HL-60 cells were cultured with serum-free RPMI 1640 medium and treated with or without of different concentrations of ASPS. After 72 h incubation, the number of cells were counted.In addition, the caspase-3 and JC-1 expression was determined by flow cytometry with Annexin V/PI double staining. The results showed that ASPS (100, 200 µg/ml) and TPO (100 ng/ml) significantly promoted CFU-GM formation in vitro. Various concentrations of ASPS and TPO also promoted the colony formation of HL-60 cells, the largest effect of ASPS was observed at a concentration of 100 µg/ml. There were no synergistic effects between TPO and ASPS on cellular proliferation. The results also showed that ASPS significantly protected HL-60 cells from apoptosis in condition of serum-free medium culture, suppressed caspase 3 activation, and reduced the cell apoptosis. It is concluded that ASPS can significantly promote the formation of bone marrow CFU-GM and the proliferation of HL-60 cells, the optimal concentration of ASPS is at 100 µg/ml. In the absence of serum inducing apoptosis, ASPS also significantly reduced the apoptosis of HL-60 cells via suppressing the activation of caspase-3.