OBJECTIVE: To study the risk factors and treatment for neutropenia of late newborns (NLN). METHODS: Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of < 1.5×10 RESULTS: Among the 46 neonates in the NLN group, 29 had a gestational age of < 32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of > 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics ( CONCLUSIONS The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.
Granulocyte Colony-Stimulating Factor ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Leukocyte Count ; Neutropenia ; Risk Factors ; Sepsis

PURPOSE: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.METHODS: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.RESULTS: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).CONCLUSIONS: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.
Asthma ; Colony-Stimulating Factors ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Haemophilus parainfluenzae ; Inflammasomes ; Inflammation ; Interleukin-13 ; Interleukin-33 ; Interleukin-5 ; Microbiota ; Necrosis ; Neisseria ; Neutrophils ; Phenotype ; Pneumonia ; Porphyromonas ; Sequence Analysis ; Sputum ; Streptococcus ; Streptococcus pneumoniae ; Veillonella

Streptococcus pneumoniae causes many people to suffer from pneumonia, septicemia, and other diseases worldwide. To identify the difference in susceptibility of and treatment efficacy against S. pneumoniae in three ICR mouse stocks (Korl: ICR, A:ICR, and B:ICR) with different origins, mice were infected with 2 × 106, 2×107, and 2×108 CFU of S. pneumoniae D39 intratracheally. The survival of mice was observed until three weeks after the infection. The three stocks of mice showed no significant survival rate difference at 2 × 106 and 2 × 107 CFU. However, the lung and spleen weight in the A:ICR stock was significantly different from that in the other two stocks, whereas the liver weight in B:ICR stock was significantly lower than that in the other two stocks. Interestingly, no significant CFU difference in the organs was observed between the ICR stocks. The level of interferon gamma inducible protein 10 in Korl:ICR was significantly lower than that in the other two stocks. The level of granulocyte colony stimulating factor in B:ICR was significantly lower than in the other two stocks. However, tumor-necrosis factor-alpha and interleukin-6 levels showed no significant difference between the ICR stocks. In the vancomycin efficacy test after the S. pneumoniae infection, both the single-dose and double-dose vancomycin-treated groups showed a significantly better survival rate than the control group. There was no significant survival difference between the three stocks. These data showed that Korl:ICR, A:ICR, and B:ICR have no susceptibility difference to the S. pneumoniae D39 serotype 2.
Animals ; Colony-Stimulating Factors ; Granulocytes ; Interferons ; Interleukin-6 ; Liver ; Lung ; Mice ; Mice, Inbred ICR ; Pneumonia ; Sepsis ; Serogroup ; Spleen ; Streptococcus pneumoniae ; Streptococcus ; Survival Rate ; Treatment Outcome ; Vancomycin ; Virulence

Recurrent pregnancy loss (RPL) is a common complication in obstetrics, affecting about 5% of women of childbearing age. An increase in the number of abortions results in escalation in the risk of miscarriage. Although concentrated research has identified numerous causes for RPL, about 50% of them remain unexplained. Pregnancy is a complex process, comprising fertilization, implantation, organ and tissue differentiation, and fetal growth, which is effectively controlled by a number of both maternal and fetal factors. An example is the immune response, in which T cells and natural killer cells participate, and inflammation mediated by tumor necrosis factor or colony-stimulating factor, which hinders embryo implantation. Furthermore, vitamin D affects glucose metabolism and inhibits embryonic development, whereas microRNA has a negative effect on the gene expression of embryo implantation and development. This review examines the causes of RPL from multiple perspectives, and focuses on the numerous factors that may result in RPL.
Abortion, Habitual ; Abortion, Spontaneous ; Colony-Stimulating Factors ; Embryo Implantation ; Embryonic Development ; Female ; Fertilization ; Fetal Development ; Gene Expression ; Glucose ; Humans ; Inflammation ; Killer Cells, Natural ; Metabolism ; MicroRNAs ; Obstetrics ; Pregnancy ; Proteomics ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Vitamin D

Cutaneous lesions of leukemia cutis (LC) by chronic neutrophilic leukemia (CNL) have been merely reported due to the rare occurrences of CNL. Furthermore cutaneous lesions in relation to clinical severity have been far less studied. A 70-year-old man presented with multiple violaceous papules and excoriations on both lower extremities. The diagnosis was LC based on histologic and laboratory evaluation and the origin was elaborated as CNL with the confirmation of colony stimulating factor 3 receptor (CSF3R) mutation. Interestingly, the patient presented clinical severity in a parallel manner to the hematologic abnormality. To the best of our knowledge, there has been no reported case of CSF3R confirmed LC in CNL featuring explicit skin eruption in relation to laboratory findings.
Aged ; Colony-Stimulating Factors ; Diagnosis ; Humans ; Leukemia ; Leukemia, Neutrophilic, Chronic ; Lower Extremity ; Skin

BACKGROUND: Osteoporosis is a geriatric disease with diminished bone density. The increase in the number of patients and medical expenses due to a global aging society are recognized as problems. Bone loss is the most common symptom of bone disease, not only osteoporosis but Paget's disease, rheumatoid arthritis, multiple myeloma, and other diseases. The main cause of this symptoms is excessive increase in the number and activity of osteoclasts. Osteoclasts are multinucleated giant cells that can resorb bone. They are differentiated and activation from monocytes/macrophages in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). METHODS: The effect of extract of Flavoparmelia sp. (EFV), a genus of lichenized fungi within the Parmeliaceae, on the differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts was examined by phenotype assay and the cell cytotoxicity was evaluated by cell counting kit-8. The osteoclast differentiation-related genes and proteins were investigated by real-time polymerase chain reaction and immunoblotting. The functional activity of osteoclast in response to EFV treatment was evaluated by an Osteo Assay plate. RESULTS: In this study, we found that EFV, a genus of lichenized fungi within the Parmeliaceae, inhibited osteoclast formation. And we investigated its inhibitory mechanism. EFV reduced RANKL-mediated osteoclast formation and activation by inhibiting expression of nuclear factor of activated T cells 1, a key factor of osteoclastogenesis. CONCLUSIONS: Taken together, our results show that EFV is a promising candidate for health functional foods or therapeutic agents that can help treat bone diseases such as osteoporosis.
Aging ; Arthritis, Rheumatoid ; Bone Density ; Bone Diseases ; Cell Count ; Functional Food ; Fungi ; Giant Cells ; Humans ; Immunoblotting ; Lichens ; Macrophage Colony-Stimulating Factor ; Macrophages ; Multiple Myeloma ; NFATC Transcription Factors ; Osteoclasts ; Osteoporosis ; Parmeliaceae ; Phenotype ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes

BACKGROUND: High-dose melphalan (HDMEL) represents the standard conditioning regimen before autologous stem cell transplant (ASCT) in multiple myeloma (MM), but recent updates have suggested combination of melphalan with bulsulfan (BUMEL) is also associated with favorable outcomes. We performed the current study to address the lack of comparative studies between the two conditioning regimens in Asian populations. METHODS: Using the Korean National Health Insurance and Korean Health Insurance Review and Assessment Service databases, 1,304 patients newly diagnosed with MM undergoing ASCT between January 2010 and December 2014 were identified. Patients were divided according to conditioning regimen (HDMEL vs. BUMEL), and after case matching, 428 patients undergoing HDMEL conditioning were compared to 107 patients undergoing BUMEL conditioning with respect to clinical course and treatment outcomes. RESULTS: The 3-year progression-free survival (PFS) was 52.5% for the HDMEL conditioning group versus 70.3% for the BUMEL conditioning group (P=0.043). The 3-year overall survival (OS) was 82.0% versus 83.5% (P=0.525), respectively. Although not statistically significant, BUMEL conditioning was associated with more platelet transfusion, while HDMEL was associated with more granulocyte colony stimulating factor support. In multivariate analysis, BUMEL conditioning was not inferior to HDMEL conditioning in regard to both PFS and OS. CONCLUSION: Our study confirmed that BUMEL is an effective and well-tolerated alternative to HDMEL conditioning, with better PFS.
Asian Continental Ancestry Group ; Busulfan* ; Colony-Stimulating Factors ; Disease-Free Survival ; Granulocytes ; Humans ; Insurance, Health ; Melphalan* ; Multiple Myeloma* ; Multivariate Analysis ; National Health Programs ; Platelet Transfusion ; Stem Cell Transplantation* ; Stem Cells*

OBJECTIVES: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. MATERIALS AND METHODS: Human fetal osteoblast cells (hFOB 1.19) were cultured with 100 µM alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. RESULTS: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. CONCLUSION: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.
Alendronate ; Bone Matrix ; Bone Morphogenetic Protein 2 ; Cell Survival ; Collagen ; Humans* ; Low-Level Light Therapy ; Macrophage Colony-Stimulating Factor ; Osteoblasts* ; Osteoclasts ; Osteogenesis ; Osteoprotegerin ; Transforming Growth Factors

Although neutrophilia can manifest from various causes, it is important to be able to distinguish chronic neutrophilic leukemia (CNL) from neutrophilic leukemoid reactions (NLR). In this paper, we describe four cases of leukocytosis with neutrophilia, including one case of CNL with a T618I mutation in colony stimulating factor 3 receptor (CSF3R) and three cases of NLR associated with malignancy or sepsis, which were initially suspected as CNL. Of the three NLR cases, one was associated with ovarian cancer, one with monoclonal gammopathy of undetermined significance and one with multiple myeloma with sepsis. This study demonstrated that confirming the clonality of myeloid cells with CSF3R T618I could contribute to making an accurate differential diagnosis between CNL and NLR in patients with solid cancers or plasma cell neoplasms caused by paraneoplastic syndromes and/or infection.
Colony-Stimulating Factors ; Diagnosis, Differential ; Humans ; Leukemia, Neutrophilic, Chronic* ; Leukemoid Reaction* ; Leukocytosis ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Myeloid Cells ; Neoplasms, Plasma Cell ; Neutrophils* ; Ovarian Neoplasms ; Paraneoplastic Syndromes ; Sepsis

The aim of this study was to determine the optimal culturing media for human CD14+ monocytes and to evaluate whether these cells are capable of differentiating into vascular endothelial cells. Human monocytes isolated from peripheral blood were cultured for 1, 3, 7, 10 or 14 days in different media containing either 10% fetal bovine serum (FBS), 10% autologous donor serum (Auto), 10% FBS with interleukin-3 and macrophage colony stimulating factor (FBS-WF) or 10% Auto and the same growth factors (AU-WF). The cells were differentiated using endothelial cell conditioning medium (EC). Viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the cells were characterized by histology, immunohistochemistry and western blot analysis. Monocytes treated with Auto, FBS-WF or AU-WF medium generated a significant higher yield of vital cells after 7 days in culture compared with FBS-only medium (mean difference (MD)=0.318, P=0.01; MD=1.83, P=0.04; or MD=0.271, P=0.01 and MD=0.318, P=0.102). All tested media led to the differentiation of monocytes into macrophages, identified by CD68, especially in the FBS-WF medium (MD=+18.3% P=0.04). Differentiation into ECs caused a significant decrease in cell viability in all media. Endothelial cell markers, including CD31, CD144, VEGF, VEGF-R2 and CD34, could not be detected. Autologous serum significantly increases the yield of monocyte-derived cells with a higher effectiveness than commonly used FBS-only serum. There is no further benefit in culturing monocytes longer than 7 days. The cultivation of monocytes in the tested media leads preferentially to differentiation into macrophages. Differentiation into endothelial cells did not take place.
Blotting, Western ; Cell Survival ; Colony-Stimulating Factors ; Endothelial Cells ; Humans* ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Interleukin-3 ; Macrophages ; Monocytes* ; Tissue Donors ; Vascular Endothelial Growth Factor A