OBJECTIVETo investigate the relationship between peripheral white blood cell count and early death rate of the patients with acute promyelocytic leukemia (APL).

METHODSThrough retrospective study, the relationship of early death rate in 116 cases newly diagnosed APL patients with maximum of peripheral blood white blood cell count should be analyzed before and after induction therapy as well as in the whole course of disease during the past 8 years.

RESULTSThere was a close relationship between the peripheral white blood cell count and the early death rate in APL patients. Peripheral blood white blood cell count in the early died patients was significantly higher than that of the survival patients (P<0.05). ROC analysis showed that the highest risk threshold of peripheral white cell count was 70×10/L (P<0.05) before treatment, while the highest risk threshold after treatment and in the whole course of disease were 96.4×10/L(P<0.05) and 91.5×10/L(P<0.01) respectively. The dealth rate of patients with highest risk threshold was significantly increased (P<0.05).

CONCLUSIONThe highest peripheral blood white blood cell count closely relates with the early death rate of patients at different time points in the whole course of disease. Control of peripheral white blood cell count may effectively reduce the early death rate of APL patients.

OBJECTIVETo investigate the potential signaling pathway that regulates the proliferation of human CD34cells stimulated by prostaglandin E2 receptor 4 agonist (EP4A) in vitro.

METHODSTwenty samples of peripheral blood containing stem cells were collected from the G-CSF mobilized healthy donors in our department of hematology. Human CD34cells were isolated by magnetic activated cell sorting (MACS) microbeads kit. The Cell Counting Kit-8 (CCK8) assay was used to determine the optimal concentration and time of EP4A to promote human CD34cell proliferation in vitro. Under the optimal condition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA level of β-catenin, and Western blot was used to assay protein expression of β-catenin and P-GSK-3β in human CD34cells treated with EP4A.

RESULTSCulturing with 10 µmol/L EP4A for 72 h, it was found that EP4A promoted human CD34cell proliferation significantly, and the proliferation rate of human CD34cells was 1.36 times higher than that of the control(P=0.002). Under the optimal condition, it was also found that EP4A enhanced the β-catenin expression at both mRNA and protein levels, and up-regulated phosphorylation of GSK-3β in human CD34cells, but these effects could be inhibited by the EP4A antagonist EP4AA.

CONCLUSIONEP4A can enhance human CD34cell proliferation in vitro by activating Wnt/β-catenin signaling pathway.

OBJECTIVETo investigate the effects of low molecular peptide of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg-10k) on the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in peripheral blood T cells and test the feasibility of differential diagnosis between pulmonary tuberculosis (PTB) and latent tuberculosis infection (LTBI) by assessing the number of Mtb-HAg-10k-stimulated IFN-γ-producing T cells.

METHODSPeripheral blood mononuclear cells (PBMCs) were separated from the peripheral blood of 10 healthy adults, 6 individuals with LTBI and 13 patients with PTB. The PBMCs were cultured in the presence of Mtb-HAg-10k obtained by ultrafiltration centrifugation, with Mtb-HAg and phytohaemagglutinin (PHA) as the controls. The proportions of TNF-α- and IFN-γ-producing cells in the T cell subsets were detected by flow cytometry (FCM), and the number of IFN-γ-producing cells from patients with PTB and LTBI was detected with ELISPOT.

RESULTSFlow cytometry showed that Mtb-HAg-10k exposure resulted in a significantly higher proportion of TNF-α-producing γδT cells than that of IFN-γ-producing γδT cells in the PBMCs (P<0.01). Compared with the PBMCs exposed to PHA, the PBMCs exposed to Mtb-HAg-10k exhibited a significantly greater proportion of γδT cells that produced both TNF-α and IFN-γ (P<0.01) but a significantly lower proportion of αβT cells producing both TNF-α and IFN-γ (P<0.01). Mtb-HAg-10k exposure of the PBMCs caused a significant reduction in the number of IFN-γ-producing cells as compared with Mtb-HAg and PHA treatments (P<0.01), and this reduction was more obvious in PBMCs from patients with PTB than in those from individuals with LTBI (P<0.01).

CONCLUSIONMtb-HAg-10k can markedly induce γδT cells in the PBMCs to produce TNF-α and IFN-γ, and detection of the number of IFN-γ-producing cells in the PBMCs following Mtb-HAg-10k stimulation helps in the differential diagnosis between pulmonary tuberculosis and latent tuberculosis infection.

BACKGROUNDMorphological changes of the vasculature system in patients with myopia have been observed by Doppler ultrasound and fundus fluorescein angiography (FFA); however, these studies have limitations. Doppler ultrasound provides low-resolution images which are mainly obtained from visualized large vessels, and FFA is an invasive examination. Optic coherence tomography (OCT) angiography is a noninvasive, high-resolution measurement for vascular density. The purpose of this study was to investigate the change of vascular density in myopic eyes using OCT angiography.

METHODSThis cross-sectional study includes a total of 91 eyes from 47 participants including control, moderate, and high myopia that were evaluated by OCT angiography. Patients with myopia were recruited from the Refractive Department, Shenzhen Aier Eye Hospital, from August 5, 2015 to April 1, 2016. Emmetropic eyes were from healthy volunteers. The vascular density at macula and optic disc regions, ganglion cell complex (GCC) thickness, and retinal nerve fiber layer (RNFL) thickness were measured. Their relationships with axial length (AL) and refractive error were analyzed. One-way analysis of variance (ANOVA), Pearson's correlation, and generalized estimating equation were used for statistical analysis.

RESULTSBoth superficial and deep macular vascular density were highest in control (25.64% ± 3.76% and 37.12% ± 3.66%, respectively), then in moderate myopia (21.15% ± 5.33% and 35.35% ± 5.50%, respectively), and lowest in high myopia group (19.64% ± 3.87% and 32.81% ± 6.29%, respectively) (F = 13.74 and 4.57, respectively; both P < 0.001). Both superficial (β = -0.850 and 0.460, respectively) and deep (β = -0.766 and 0.396, respectively) macular vascular density were associated with AL and spherical equivalent (all P < 0.001). Superficial macular vascular density was associated with GCC thickness (β = 0.244, P = 0.040), independent of spherical equivalent. The vascular density in optic disc region had no difference among the three groups, and it was not associated with AL, spherical equivalent, or RNFL thickness.

CONCLUSIONOur results suggested that with the increase of myopia, the vascular density decreased in macular region, but not in optic disc region.

Adult ; Cross-Sectional Studies ; Eye ; blood supply ; Female ; Fluorescein Angiography ; Humans ; Macula Lutea ; pathology ; physiopathology ; Male ; Middle Aged ; Myopia ; pathology ; physiopathology ; Optic Disk ; pathology ; physiopathology ; Prospective Studies ; Retina ; pathology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Tomography, Optical Coherence ; Young Adult

BACKGROUNDSurfactant protein-A (SP-A) contributes to the regulation of sepsis-induced acute kidney injury. In a previous study, we demonstrated that the expression of SP-A in the human renal tubular epithelial (HK-2) cells can be stimulated by lipopolysaccharide (LPS). The present study evaluated the possible signal-transducing mechanisms of LPS-induced SP-A biosynthesis in the HK-2 cells.

METHODSTetrazolium salt colorimetry (MTT) assay was used to detect cell viability of HK-2 cells after LPS stimulation on different time points. HK-2 cells were stimulated with 100 ng/ml of LPS for different durations to determine the effects of LPS on SP-A and toll-like receptor 4 (TLR4) messenger RNA (mRNA) expression, as well as phosphorylation of mitogen-activated/extracellular signal-regulated kinase (MEK) 1, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38MAPK), and nuclear factor-kappa B (NF-κB) inhibitor-alpha (IkB-α). Then, HK-2 cells were pretreated with CLI-095, a TLR4 inhibitor, to analyze mRNA and protein levels of SP-A and TLR4 and expression of NF-κB in the cytoplasm and nucleus of HK-2 before LPS exposure.

RESULTSHK-2 cells exposed to 100 ng/ml of LPS for 1, 6, and 24 h did not affect cell viability which showed no toxic effect of 100 ng/ml LPS on cells (P = 0.16); however, the biosynthesis of SP-A mRNA and protein in HK-2 cells was significantly increased (P = 0.02). As to the mechanism, LPS enhanced transmembrane receptor TLR4 protein expression. Sequentially, LPS time dependently augmented phosphorylation of MEK1, ERK1/2, and p38MAPK. In addition, levels of phosphorylated IκB-α and nuclear NF-κB were augmented with LPS exposure for 2 h. LPS-induced SP-A and TLR4 mRNA as well as NF-κB expression were significantly inhibited by pretreatment with CLI-095.

CONCLUSIONSThe present study exhibited that LPS can increase SP-A synthesis in human renal epithelial cells through sequentially activating the TLR4-related MEK1-ERK1/2-NF-κB-dependent pathway.

Cell Line ; Cell Survival ; drug effects ; physiology ; Colorimetry ; Humans ; Kidney ; cytology ; metabolism ; Lipopolysaccharides ; toxicity ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; NF-kappa B ; metabolism ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Sulfonamides ; pharmacology ; Tetrazolium Salts ; chemistry ; Toll-Like Receptor 4 ; antagonists & inhibitors ; metabolism

Clinical practice guideline (CPG) should be concise and readability, which can be possible to implement CPG into practice smoothly. A formal published CPG can't load its developing process and details. An editorial explanation of CPG is much useful to show details and logic process of developing CPG. Although there are many different standards for developing CPG, being nothing to do with process management of CPG. By referring to editorial explanation on international standards, a request for CPG was investigated in this study. An editorial explanation for clinical practice guideline should be transparency, logic and traceable. A good editorial explanation could make users or readers to learn what goes on behind the scenes. A standardized editorial explanation could supervise the GCP developing and improve the quality of GCP.

To predit the mechanism of metabolic drug-drug interactions of hydroxygenkwanin with other drugs, we investigated the inhibition inhibitory effect of hydroxygenkwanin on UGTs and UGT1A1 activities of different liver microsomes. In the present study, 4-nitrophenol (4-NP) and β-estradiol were elected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. The results showed that, hydroxygenkwanin significantly inhibited UGTs activity in rat, mouse and human liver microsomes. UGT1A1 activity was inhibited by hydroxygenkwanin to varying degrees, with IC₅₀ about 190, 10.93, 20.07, 76.31 μmol•L⁻¹ in mouse liver microsome(MLM), rat liver microsome (RLM) and recombinant UGT1A1, and human liver microsome (HLM), respectively. The inhibition types were competitive inhibition (RLM, HLM) and linear mixed-typed linear inhibition (recombinant UGT1A1). The order for the inhibitory intensity was RLM>rUGT1A1>HLM>MLM. In conclusion, hydroxygenkwanin has an inhibitory effect on UGTs and UGT1A1 activities of different liver microsomes, with differences in species, indicating its potential drug interactions based on UGT1A1 enzyme. This study aims to provide a reliable experimental basis for its further research and development of hydroxygenkwanin, and provide theoretical reference for the clinic drug combination research.

Fifteenlanostane triterpenoids were isolated from the ethanol extract of Ganoderma theaecolum by means of preparative HPLC,column chromatography over silica gel,ODS and were identified as lucidone C(1),lucidone D(2),7-oxo-ganoderic acid Z2(3),7-oxo-ganoderic acid Z(4),ganoderenicacid H(5),ganoderenic acid B(6),3β,7β-dihydroyl-11,15,23-trioxo-lanost-8,16-dien-26-oic acid(7),3β,7β-dihydroyl-11,15,23-trioxo-lanost-8,16-dien-26-oic acid methyl ester(8),ganolucidic acid B(9),ganolucidate F(10),methyl ganoderate C2(11),ganoderic acid ζ(12),ganoderic acid AP3(13),methyl ganoderate B(14),and ganoderol B(15). Compounds 1-15 were isolated from this specie for the first time.

OBJECTIVETo identify differentially expressed microRNAs (miRNAs) related to lung adenocarcinoma in Xuanwei region and predict their target genes and related signaling pathways based on bioinformatic analysis.

METHODSHigh-throughput microarray assay was performed to detect miRNA expression profiles in 34 paired human lung adenocarcinoma and adjacent normal tissues (including 24 cases in Xuanwei region and 10 in other regions). Gene ontology and KEGG pathway analyses were used to predict the target genes and the regulatory signaling pathways.

RESULTSThirty-four miRNAs were differentially expressed in lung adenocarcinoma tissues in cases in Xuanwei region as compared with cases in other regions, including 23 upregulated and 11 downregulated miRNAs. The predicted target genes included GF, RTK, SOS, IRS1, BCAP, CYTOKINSR, ECM, ITGB, FAK and Gbeta;Y involving the PI3K/Alt, WNT and MAPK pathways.

CONCLUSIONThe specific microRNA expression profiles of lung adenocarcinoma in cases found in Xuanwei region allow for a better understanding of the pathogenesis of lung adenocarcinoma in Xuanwei. The predicted target genes may involve the PI3K/Alt, WNT and MAPK pathways.

Adenocarcinoma ; genetics ; metabolism ; Computational Biology ; Gene Expression Profiling ; Humans ; Lung ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Signal Transduction