ABSTRACT
Objective:To explore the clinical value of heparin binding protein (HBP) in bronchoalveolar lavage fluid (BALF) for diagnosis and differential diagnosis of bacterial pneumonia.Methods:Eighty eight patients with pulmonary infection from the respiratory department of the Fourth Affiliated Hospital of Anhui Medical University from January 2019 to January 2021 were enrolled in the study, including 48 cases of bacterial pneumonia and 40 cases of non-bacterial pneumonia; meanwhile, 40 non-pulmonary infection patients were also enrolled as the control group. The BALF levels of HBP, procalcitonin (PCT), interleukin-6 (IL-6) were measured, and the clinical values of the above indexes in differential diagnosis of bacterial and non-bacterial pneumonia were analyzed.Results:The BALF levels of HBP and IL-6 in bacterial pneumonia group were significantly higher than those of the non-bacterial pneumonia group and the control group ( P<0.05). ROC curve showed that the areas under the curve (AUC) of HBP and IL-6 were 0.930 and 0.893 for the early diagnosis of bacterial pneumonia; and the sensitivity was 88.5% and 82.7%, the specificity was 92.5% and 92.5%, respectively. Combined detection of HBP and IL-6, the AUC was 0.942 and the sensitivity was 94.2% and the specificity was 95.0%. When they were used to distinguish bacterial pneumonia, the AUC of HBP and IL-6 were 0.890 and 0.777, and the sensitivities were 80.8% and 71.2%, and the specificity were 91.7% and 75.0%, respectively. Combined detection of HBP and IL-6, the AUC was 0.902, and the sensitivity was 96.2% and the specificity was 79.2%. Conclusions:BALF HBP and IL-6 have good clinical value in the early diagnosis and distinguishing bacterial pulmonary infection and the joint value of the two is better.
ABSTRACT
Objective To investigate the characteristics of repair of DNA double strand breaks (DSB) induced by high-LET α-particle irradiation and their relationship with chromatin structure in the G0 lymphocytes of human peripheral blood,in order to provide the experimental basis for the judgement and dose evaluation of internal α-particle radiation.Methods Peripheral whole blood were collected from four healthy adults and lymphocytes were separated.A monocellular layer of human lymphocytes attached in Mylar film were irradiated with 0 and 0.5 Gy of α-particles and the lymphocytes suspensions were irradiated with 0 and 0.5 Gy of γ-rays.The formations of γH2AX foci as a surrogate marker of DSB and Rad51 foci as a marker of homologous recombination (HR) repair and their spatial localization in chromatin structure were measured by immunofluorescence staining technique at 10 min-48 h post-irradiation.Results Linear-γH2AX foci tracks were observe at 10 min-2 h post-irradiation in lymphocytes exposed to α-particle irradiation(t =11.12,14.40,16.56,P ＜ 0.05),and almost completely disppeared at 6 h postirradiation.The frequencies of γH2AX foci peaked at 30 min after α-particle irradiation (t =51.72,P ＜0.05) and then decreased rapidly during 6 h post-irradiation (t =29.83,P ＜ 0.05).The average number of foci remained only about 16％ at 24-48 h post-irradiation.Moreover,27％ of γH2AX foci located at DAPI-bright heterochromatin region at 10 min after α-particle radiation,suggesting that the efficacy of DSB repair may be decreased.In contrast,at 10 min-48 h after γ-ray irradiation,no linear γH2AX foci track was observed and the γH2AX foci diffused randomly in nucleus and predominantly located in DAPI-weak euchromatin region.The numbers of formative and residual γH2AX foci after γ-ray irradiation were significantly less than those after α-particle radiation.During 30 min-2 h after α-particle and γ-ray irradiation,the frequencies of Rad51 foci slightly but not significantly increased in comparison with background level,and the frequencies of co-localization of Rad51 foci and γH2AX foci were only 3％-8％.Conclusions The formation of linear γH2AX foci tracks induced by high-LET α-particle irradiation in Go human lymphocyte could be used as biological indicator to estimate whether a person has been exposed to internal α-particle radiation.Prolonged persistence of residual γH2AX foci may be applicable for biological dosimetry.
ABSTRACT
Objective To investigate the radiosensitization effect of antihelminthic niclosamide on human triple-negative breast cancer MDA-MB-231 cells and the potential mechanism related to Wnt/β-catenin signaling pathway.Methods Four methyl thiazolyl tetrazolium(MTT) assay was used to measure the effect of niclosamide on cell viability at different concentrations and 50％ inhibitory concentration(IC50)value was calculated.MDA-MB-231 cells were divided into 4 groups:untreated control,niclosamide treatment alone group,radiation alone group and niclosamide plus radiation treatment group.The cells with or without 1.0 and 1.5 μmol/L niclosamide pre-treatment were irradiated with 137Cs γ-rays at doses of 0,2,4 and 6 Gy.Cell survival was assayed with the colony formation method,radiation-induced γH2AX foci was analyzed with immunofluorescence,cell cycle progression was assayed with flow cytometry,and the changes of phospho-and non-phospho-β-catenin and Cyclin D1 protein expressions were measured with Western blot.Results Niclosamde obviously inhibited the viability of MDA-MB-231 cells in a dosedependent manner with a IC50 value of 13.63 μmol/L.Pretreatment of cells with 1.0 and 1.5 μmol/L niclosamide evidently enhanced the radiosensitivity of MDA-MB-231 cells to γ-rays,and the values of SER were 1.37 and 1.62,respectively.Niclosamide pretreatment significantly increased radiation-induced γH2AX foci formation(t =3.91,P ＜0.05),diminished the radiation-induced G2/M arrest(t =8.05,P ＜0.01),and inhibited radiation-induced expressions of phospho-β-catenin (S675),non-phospho-β-catenin and Cyclin D1 proteins in MDA-MB-231 cells.Conclusions Niclosamide significantly can enhance the sensitivity of MDA-MB-231 cells to γ-ray irradiation through inhibiting Wnt/β-catenin signaling pathway,which results in the inhibition of DNA DSBs repair and the reduction of radiation-induced G2/M arrest.Wnt/β-catenin signaling pathway may serve as an ideal molecular target for radiosensitization of triplenegative breast cancer.