ANTIGEN ASSOCIATION OF J6-1 CELL MEMBRANE ASSOCIATEDFACTOR RECEPTOR WITH MACROPHAGE COLONYSTIMULATING FACTOR RECEPTOR

Objective: To verify the antigen association of MAF-J6-1 receptor with M-CSFR and to further study the role of M-CSF and its receptor mediated juxtacrine in promoting leukemic cell proliferation. Methods: Monoclonal antibody (McAb) of MAF-J6-1R RE2 and polyclonal antibody (PolyAb) of rhM-CSFR were prepared. The specificity of McAb RE2 to M-CSFR was confirmed by indirect ELISA, cross-neutralizing assay with J6-1 cell colony formation and neutralization test by ELISA. Results: the reactive activity of purified RE2 to M-CSFR was over 1: 16000. The inhibitory activity of M-CSFR and MAF-J6-1R could be blocked by RE2 and anti-M-CSFR antibody. The reactivity of RE2 to M-CSFR could be reduced by M-CSFR. Conclusion: The specificity of RE2 to M-CSFR was confirmed and the antigen association of MAF-J6-1R with M-CSFR was proved. It suggests that M-CSF and its receptor mediated auto-juxtacrine stimulation could be an operative mechanism in either leukemia or nonhematological malignancies.

IMMUNOHISTOCHEMICAL OBSERVATION OF MACROPHAGE COLONY STIMULATING FACTOR AND ITS RECEPTOR IN BREAST CANCER AND HEPATOMA TISSUES

Objective: To study the potential role of cellular macrophage colony-stimulating factor (cM-CSF) and cellular macrophage colony-stimulating factor receptor (cM-CSF-R) with breast cancer and hepatoma and search the way for clinical application. Methods: Frozen surgical specimens from 48 breast cancer patients, including 29 cases of histological grade II and 19 eases of grade III, and 16 hepatoma patients were investigated by Avidin Biotin Complex (ABC) immunohistochemical assay with anti-M-CSF monoclonal antibody (Mab) and anti-M-CSF-R Mab. Pathohistological examination was performed as well. Results: cM-CSF and cM-CSF-R were detected in tested specimens. The expression levels of cM-CSF and cM-CSF-R in grade III group were higher than in grade II group and more higher than control group hyperplasia of breast. Hepatoma tissues also showed higher expression level of cM-CSF and cM-CSF-R than normal adult and fetal liver. Conclusion: Breast cancer and hepatoma tissues presented higher expression levels of cM-CSF and cM-CSF-R than control and expression level might be related with tumor’s process.

CO-EXPRESSION OF MACROPHAGE COLONY-STIMULATING FACTOR WITH ITS RECEPTOR IN HUMAN HEPATOMA CELLS AND ITS POTENTIAL ROLES

Objective: To investigate the potential role of macrophage colony-stimulating factor (M-CSF) and macrophage colony-stimulating factor receptor (M-CSF-R) on the growth of human hepatoma cells. Methods: Specimens of different origin, including tissues of human hepatocellular carcinoma (HCC), human fetal liver (FL) and normal liver (NL), the hepatoma cell lines, as well as the peripheral blood mononuclear cells (PBMC) from patients with HCC or liver metastatic tumor (LMT), were used to detect the expression levels of M-CSF and M-CSF-R by ABC immunohistochemistry staining and reverse transcription polymerase chain reaction methods the expression levels of M-CSF and M-CSF-R. Influence of monoclonal antibody against M-CSF (B5) or M-CSF-R (RE2) on proliferation ability of hepatoma cell linesin vitro was also studied. Results: The results showed that hepatoma tissues produced elevated levels of both M-CSF and M-CSF-R compared with those of fetal liver (P<0.001). The M-CSF/M-CSF-R expression levels of PBMC from hepatoma patients were higher than those of LMT patients (P<0.01,P<0.05) and the normal people (P<0.001). The hepatoma cell lines showed strong positive for M-CSF and M-CSF-R production. Both B5 and RE2 displayed a dose-dependent inhibitory effect on the growth and proliferation of hepatoma cells. Conclusion: The study indicates a co-expression model for M-CSF-R in hepatoma cells, suggesting an involvement of M-CSF/M-CSF-R in growth signaling of those malignant cells. The M-CSF/M-CSF-R seems to function through an autonomy mechanism in human hepatoma.

Preclinical evaluation of herpes simplex virus armed with granulocyte-macrophage colony-stimulating factor in pancreatic carcinoma

AIM: To investigate the therapeutic efficacy and mechanisms of action of oncolytic-herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating factor(HSVGM-CSF) in pancreatic carcinoma.METHODS: Tumor blocks were homogenized in a sterile grinder in saline.The homogenate was injected into the right armpit of each mouse.After vaccination,the mice were randomly assigned into four groups: a control group,a high dose HSVGM-CSFgroup [1 × 107plaque forming units(pfu)/tumor],a medium dose HSVGM-CSF group(5 × 106pfu/tumor) and a low dose HSVGM-CSF group(5 × 105pfu/tumor).After initiation of drug administration,body weights and tumor diameters were measured every 3 d.Fifteen days later,after decapitation of the animal by cervical dislocation,each tumor was isolated,weighed and stored in 10% formaldehyde solution.The drug effectiveness was evaluated according to the weight,volume and relative volume change of each tumor.Furthermore,GM-CSF protein levels in serum were assayed by enzyme-linked immunosorbent assays at 1,2,3 and 4 d after injection of HSVGM-CSF.RESULTS: Injection of the recombinant mouse HSV encoding GM-CSF resulted in a significant reduction in tumor growth compared to the control group,and dosedependent effects were observed: the relative tumor proliferation rates of the low dose,medium dose and high dose groups on 15 d after injection were 45.5%,55.2% and 65.5%,respectively.The inhibition rates of the tumor weights of the low,middle,and high dose groups were 41.4%,46.7% and 50.5%,respectively.Furthermore,the production of GM-CSF was significantly increased in the mice infected with HSVGM-CSF.The increase in the GM-CSF level was more pronounced in the high dose group compared to the other two dose groups.CONCLUSION: Our study provides the first evidence that HSVGM-CSFcould inhibit the growth of pancreatic cancer.The enhanced GM-CSF expression might be responsible for the phenomenon.

CONSTRUCTION OF EUKARYOTIC EXPRESSION VECTOR WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE

Objective: To construct the eukaryotic expression vector that express human granulocyte-macrophage colony-stimulating factor (hGM-CSF) gene for making highly express in mammalian cells. Methods: Extract totally RNA from the induced human fetal lung (HFL) cell line. HGM-CSF cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR), and then directionally subcloned into the HindIII and EcoRI site on the pcDNA3.1 plasmid, which was controlled by the CMV promoter, to form the recombinant expressing vector pcDNA3.1-GM-CSF. Results: The PCR amplification was identified and the sequence was analyzed, the results showed that hGM-CSF was properly inserted into the vector and the sequence was correct.

Granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells for the treatment of ischemic stroke

Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells （GM-CSF-BMSCs） into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.

DETERMINATION OF SERUM SOLUBLE MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR LEVELS IN PATIENTS WITH HEMATOLOGICAL DISEASES

Objective: To investigate the serum levels of soluble macrophage colony-stimulating factor receptor (M-CSFsR) in normal subjects and patients with hematological diseases and its clinical implications in hematological diseases. Methods: The concentration of M-CSFsR was determined by ELISA. The serum M-CSFsR was identified and characterized by immunoprecipitation and Western blotting. Results: The mean serum level of M-CSFsR of 123 normal individuals was 0.48 ng/ml ± 0.41 ng/ml. Immunoprecipitation and Western blotting assay revealed a ～ 90kD band of serum M-CSFsR. The mean serum M-CSFsR level of 60 patients with acute lymphoblastic leukemia (ALL), 36 patients with acute myeloblastic leukemia (AML), 13 patients with myelodysplastic syndrome (MDS) and 42 patients with aplastic anemia (AA) .were 0.22 ng/ml±0.23 ng/ml, 0.17 ng/ml±0.16 ng/ml, 0.19 ng/ml±0.16 ng/ml and 0.23 ng/ml±0.21 ng/ml, respectively, which were significantly lower than that of normal subjects (P=0.002 ,P<0.0001,P<0.0001 andP<0.0001). The mean serum M-CSFsR level of 51 idiopathic thrombocytopenic purpura (ITP) patients was significantly higher than that of normal subjects (2.05 ng/ml±2.75 ng/ml,P<0.0001). Conclusion: The serum M-CSFsR levels of patients with ALL, AML, MDS and AA were significantly lower, while the level of patients with ITP was significantly higher than that of normal individuals. Patients with severe ITP (platelet count<30×l09/L) had the highest M-CSFsR level. It suggested that the abnormal levels of serum M-CSFsR may associate with some hematological diseases and may contribute to the pathological process.

ENHANCEMENT OF NIH3T3 CELL PROLIFERATION BY EXPRESSING MACROPHAGE COLONY STIMULATING FACTOR IN NUCLEI

Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to the C-terminal of the expressed protein and direct the protein into the cell nuclei. The constructed plasmid was transferred into NIH3T3 cells and the cell clones were selected by G-418 selection. Cell clones stable expressing target protein were identified by RT-PCR, ABC immunohistochemistry assayand Western blot. Cell growth kinetics analyses throughgrowth curves, cell doubling time, MTT test and anti-sense oligodeoxynucleotide (ASODN) inhibiting cell growth testwere performed to identify cells proliferation potential.Results: The transfected cells showed elevated proliferation potential over the control cells. Conclusion: Abnormalappearance of M-CSF in nucleus could enhance cellproliferation, which suggests that cytokine isoforms within cell nucleus might play transcription factor-like role.

EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR GENE ENCODED VACCINIA VIRUS VECTOR ON MURINE PULMONARY METASTATIC MELANOMA

A recombinant vaccinia virus expressing murine granulocyte-macrophage colony-stimulating factor (VVGM-CSF) was tested for its antitumor activity.Murine pulmonary metastasis was established by injecting 20×10~5 B16F10 melanoma cells into the tail vein of C57BL/6 mice. Three days after B16F10 inoculation,WGM-CSF or VVTK, a thymidine kinase gene deficient control vaccinia virus, were injected intraperitoneally twice weekly for 2 weeks. Two weeks later, the mice were sacrificed and pulmonary metastasis fool counted.The results demonstrated that VVGM-CSF treatment significantly decreased the number of pulmonary metastasis and prolonged the survival time of tumorbearing mice. Cytotoxic and phagocytic activities of the peritoncal macrophages were found to be markedly elevated in mice treated with WGM-CSF. Nitric oxide released from the macrophages was also found to be increased. These data, together with our other results,strongly demonstrated that continuous secretion of GMCSF and activation of macrophages might pal-tially explain the therapeutic effects of VVGM-CSF on murine pulmonary metastasis.

Antiviral Activity of Silkworm Expressed Recombinant Human Macrophage Colony-Stimulating Factor in Vitro and Its Mechanism

Cells, pretreated with the recombinant human macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm larvae, were inoculated with several viruses to observe the effect of rhM-CSF on viral replication. The results showed that in cultures of fibroblast derived from human fetal skin-muslce tissues infected with the viruses (including VSV, rhinovirus, influenza virus type A3, HSV-1, HSV-2, adenovirus type 6 and type 11), rhM-CSF inhibited the virus-induced cytopathy, which defered or relieved the cytophathy and that in the cells derived from breast feeding rabbit kidney infected with HSV-1, rhM-CSF reduced titer of the virus in a rhM-CSF dose-dependent pattern,in which rhM-CSF with the dose of 1×106 U/L made the viral titer drop dwon over 200 times. This antiviral activity of rhM-CSF could be partially neutralized by anti-IFN-βMcAb, but not by antiTNF-α, anti-IFN-α, or anti-IFA-γ McAb, indicating the mechanism of the antiviral activity of MCSF is related to the induction of IFN-β.

Molecular cloning, pathologically-correlated expression and functional characterization of the colony- stimulating factor 1 receptor （CSF-1R） gene from a teleost, Plecoglossus altivelis

Colony-stimulating factor 1 receptor （CSF-1R） is an important regulator of monocytes/macrophages （MO/MФ）. Although several CSF-1R genes have been identified in teleosts, the precise role of CSF- 1R in ayu （Plecoglossus altivelis） remains unclear. In this study, we characterized the CSF-1R homologue from P. altivelis, and named it PaCSF-1R. Multiple sequence alignment and phylogenetic tree analysis showed that PaCSF-1R was most closely related to that of Japanese ricefish （Oryzias latipes）. Tissue distribution and expression analysis showed that the PaCSF-1R transcript was mainly expressed in the head kidney-derived MO/MФ, spleen, and head kidney, and its expression was significantly altered in various tissues upon Vibrio anguillarum infection. After PaCSF-1R neutralization for 48 h, the phagocytic activity of MO/MФ was significantly decreased, suggesting that PaCSF-1R plays a role in regulating the phagocytic function of ayu MO/M（P.

可视化分析GM-CSF在免疫炎症中的研究现状

目的通过文献计量学方法对粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF)在免疫炎症方面相关研究现状、热点及发展趋势进行分析。方法在Web of Science核心数据库中检索1990年1月1日至2024年1月1日的相关文献,并应用CiteSpace软件对数据进行可视化分析。结果共纳入1219篇GM-CSF在免疫炎症方面相关文献,发文量整体呈上升趋势,美国以445篇居全球第一。发文量最高的机构是墨尔本大学25篇;发文量并列第一的作者是Jordana M和Becher B,每人10篇,被引次数最高的作者是Hamilton JA 128次;被引次数最多的期刊是Journal of Immunology 986次,GM-CSF在免疫炎症中相关热点主要包括inflammation、dendritic cell、T cell等,近几年的研究热点集中在immunity和microglia。结论随着GM-CSF在免疫炎症领域研究不断深入,其学术影响力也逐渐广泛,未来研究方向在于探索GM-CSF在免疫炎症领域中的作用机制和靶向治疗。

金刚藤胶囊联合桂枝茯苓胶囊治疗慢性盆腔炎的疗效及对血清GM-CSF、MMP-2水平的影响

【目的】分析金刚藤胶囊联合桂枝茯苓胶囊治疗湿热瘀结型慢性盆腔炎的疗效及对血清粒细胞-巨噬细胞集落刺激因子(GM-CSF)、基质金属蛋白酶2(MMP-2)水平的影响。【方法】将90例湿热瘀结型慢性盆腔炎患者随机分为联合组和单药组,每组各45例。单药组患者给予桂枝茯苓胶囊治疗,联合组患者在单药组的基础上联合金刚藤胶囊治疗,疗程为2周并随访1个月。观察2组患者治疗前后中医证候积分和血清GM-CSF、MMP-2水平的变化情况,比较2组患者的临床疗效、症状缓解时间、疾病复发和不良反应发生情况。【结果】(1)疗效方面,治疗2周后,联合组的总有效率为93.33%(42/45),单药组为66.67%(30/45),组间比较,联合组的疗效明显优于单药组(P<0.01)。(2)中医证候积分方面,治疗后,2组患者的下腹疼痛、腰骶疼痛、带下量多、月经量多、经行腹痛、神疲乏力等各项中医证候积分均较治疗前明显降低(P<0.05),且联合组对各项中医证候积分的降低幅度均明显优于单药组(P<0.05)。(3)症状缓解时间方面,联合组患者治疗后的白带恢复正常时间、下腹坠胀和腹痛缓解时间均较单药组明显缩短(P<0.01)。(4)血清学指标方面,治疗后,2组患者的血清GM-CSF、MMP-2水平均较治疗前明显降低(P<0.05),且联合组对血清GM-CSF、MMP-2水平的降低幅度均明显优于单药组(P<0.05或P<0.01)。(5)疾病复发和不良反应方面,联合组的复发率和不良反应发生率分别为11.11%(5/45)、13.33%(6/45),均明显低于单药组的35.56%(16/45),差异均有统计学意义(P<0.05或P<0.01)。【结论】金刚藤胶囊联合桂枝茯苓胶囊治疗,可以显著提高湿热瘀结型慢性盆腔炎的临床疗效,有效缩短症状缓解时间,降低血清GM-CSF、MMP-2水平。

血清TIMP-1、M-CSF联合检测对老年病人乙型肝炎后肝硬化早期诊断的价值

目的探讨血清基质金属蛋白酶抑制因子-1(TIMP-1)、巨噬细胞集落刺激因子(M-CSF)水平对老年病人乙型肝炎后肝硬化早期诊断的价值。方法回顾性纳入2020年3月至2022年5月医院收治的97例老年乙型肝炎后肝硬化病人为研究组,另回顾性纳入医院同时间段收治的125例老年乙型肝炎病人为对照组。根据病人肝硬化程度将研究组分为肝硬化A级39例、肝硬化B级33例、肝硬化C级25例。比较各组间血清TIMP-1、M-CSF水平的差异,分析血清TIMP-1水平与血清M-CSF水平的相关性,分析老年乙型肝炎病人发生肝硬化的影响因素,分析血清TIMP-1、M-CSF联合检测对老年乙型肝炎病人发生肝硬化的诊断价值。结果研究组总胆红素(TBIL)、甲胎蛋白(AFP)水平高于对照组,凝血酶原时间(PT)长于对照组(P<0.01),白蛋白(ALB)水平低于对照组(P<0.01);研究组血清TIMP-1、M-CSF水平高于对照组(P<0.01);血清TIMP-1、M-CSF水平随着肝硬化程度加重而逐渐升高(P<0.05);血清TIMP-1水平与血清M-CSF水平呈正相关(P<0.05)。血清TBIL、TIMP-1、M-CSF、ALB及PT为老年乙型肝炎病人发生肝硬化的影响因素(P<0.05)。血清TIMP-1、M-CSF水平及二者联合诊断老年乙型肝炎病人发生肝硬化的AUC分别为0.821、0.813、0.896(P<0.05),且二者联合诊断价值更高(P<0.05)。结论血清TIMP-1、M-CSF水平在早期诊断老年病人乙型肝炎后肝硬化中具有重要价值,且二者联合具有更高的诊断价值。

进行气管插管的颅脑外伤患者血清GM-CSF和HMGB1水平及其与并发肺部感染的关系

目的探讨血清粒-巨噬细胞集落刺激因子(GM-CSF)、高迁移率族蛋白B1(HMGB1)与进行气管插管的颅脑外伤患者并发肺部感染的关系。方法选取2020年12月至2022年12月华北医疗健康集团峰峰总医院收治的156例进行气管插管的颅脑外伤患者作为颅脑外伤组,根据是否出现肺部感染将进行气管插管的颅脑外伤患者分为感染组和未感染组,另根据临床肺部感染评分(CPIS)将进行气管插管的颅脑外伤并发肺部感染患者分为重度感染组和轻度感染组,并选取同期在华北医疗健康集团峰峰总医院体检的体检健康者60例作为对照组。采用酶联免疫吸附试验(ELISA)测定所有研究对象血清GM-CSF、HMGB1水平;分析进行气管插管的颅脑外伤并发肺部感染患者血清GM-CSF、HMGB1水平与CPIS的关系;采用多因素Logistic回归分析进行气管插管的颅脑外伤患者并发肺部感染的影响因素;采用受试者工作特征(ROC)曲线分析血清GM-CSF、HMGB1对进行气管插管的颅脑外伤患者并发肺部感染的预测价值。结果与对照组相比,颅脑外伤组患者血清GM-CSF、HMGB1水平均明显升高(P<0.05)。感染组患者血清GM-CSF、HMGB1水平显著高于未感染组(P<0.05)。重度感染组21例,轻度感染组45例。与轻度感染组患者相比,重度感染组患者血清GM-CSF、HMGB1水平及CPIS均显著升高(P<0.05)。相关分析结果显示,感染组患者血清GM-CSF、HMGB1水平与CPIS均呈正相关(r=0.408、0.435,P<0.05)。多因素Logistic回归分析结果显示,年龄≥60岁、入院时GCS评分≥6分、合并糖尿病、GM-CSF水平升高、HMGB1水平升高均是进行气管插管的颅脑外伤患者并发肺部感染的危险因素(P<0.05)。ROC曲线分析结果显示,GM-CSF、HMGB1联合预测进行气管插管的颅脑外伤患者并发肺部感染的曲线下面积(AUC)为0.912(95%CI:0.860~0.963),明显大于GM-CSF、HMGB1单项预测的AUC[0.826(95%CI:0.756~0.895)、0.819(95%CI:0.743~0.896)],差异均有统计学意义(Z=1.972,P=0.049;Z=1.984,P=0.047)。结论血清GM-CSF、HMGB1水平在进行气管插管的颅脑外伤并发肺部感染的患者中升高,是进行气管插管的颅脑外伤患者发生肺部感染的危险因素,2项指标联合检测对进行气管插管的颅脑外伤患者并发肺部感染具有良好的预测价值。

血清GM-CSF、IGF-1联合检测在妊娠期糖尿病患者不良妊娠结局诊断中的价值

目的:分析血清粒细胞-巨噬细胞集落刺激因子(GM-CSF)、胰岛素样生长因子-1(IGF-1)联合检测在妊娠期糖尿病(GDM)患者不良妊娠结局诊断中的价值。方法:选取2021年6月至2023年3月该院收治的83例GDM患者设为研究组,根据妊娠结局将其分为不良结局患者(n=24)和良好结局患者(n=59),另选取同期160名健康孕妇作为对照组,比较两组及不同妊娠结局GDM患者血清GM-CSF、IGF-1水平,绘制受试者工作特征(ROC)曲线,分析血清GM-CSF、IGF-1单项及联合检测在GDM患者不良妊娠结局诊断中的价值。结果:研究组血清IGF-1水平低于对照组,GM-CSF水平高于对照组,差异均有统计学意义(P<0.05);不良结局患者IGF-1水平低于良好结局患者,GM-CSF水平高于良好结局患者,差异均有统计学意义(P<0.05);ROC曲线分析结果显示,血清IGF-1、GM-CSF单项及联合检测诊断GDM患者不良妊娠结局的曲线下面积分别为0.821、0.822、0.912,均具有一定诊断价值,且联合检测诊断价值最高。结论:血清GM-CSF、IGF-1联合检测在GDM患者不良娠结局诊断中的价值高于二者单项检测。

Pharmacokinetics of recombinant human granulocyte macrophage colony-stimulating factor in Macaca mulata

目的：研究重组人粒细胞巨噬细胞集落刺激因子（ｒｈＧＭＣＳＦ）在恒河猴体内的药物动力学．方法：用酶连接免疫吸附测定法检测血浆中ｒｈＧＭＣＳＦ的含量．结果：ｉｖｒｈＧＭＣＳＦ后血药浓度时间曲线符合三房室模型．第１，２和３相的Ｔ１２分别为００５－００７ｈ，０１４－０５８ｈ和１４－４１ｈ．ＡＵＣ随剂量成比例增加．ｉｖ高剂量和低剂量的Ｃｌ和Ｋ１０都相似．ｓｃｒｈＧＭＣＳＦ后血药浓度的峰值为０９３±０１６μｇ·Ｌ－１，达峰时间为２６５±０１４ｈ，生物利用度为０６１．结论：恒河猴ｒｈＧＭＣＳＦ药物动力学数据为临床试验提供有用参考．

A pilot study on the combined therapy of granulocyte-macrophage colony-stimulating factor and hepatitis B vaccine on chronic hepatitis B virus carrier children

Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte macrophage colony stimulating factor (GM CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac) Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four dose schedule HBV DNA quantification and other HBV serological markers were tested before and after the four dose therapy Results Twelve children in each group completed the study Of them, 3 children in the GM CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM CSF group and 10 in the HBIG group One from each group had an HBeAg/anti HBe seroconversion after the treatment The quantity of HBV DNA was significantly lower after the treatment ( P =0 023) in GM CSF group, but was not significantly reduced in HBIG group No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group Conclusion Combined GM CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis

血清M-CSF、sTNFRⅠ在宫颈上皮内瘤变与宫颈癌鉴别诊断中的作用

目的:探究血清巨噬细胞集落刺激因子(M-CSF)、可溶性肿瘤坏死因子受体Ⅰ(sTNFRⅠ)在宫颈上皮内瘤变(CIN)与宫颈癌鉴别诊断中的作用。方法:选取217例宫颈癌患者(宫颈癌组)及231例CIN患者[CINⅠ级109例(CINⅠ组)、CINⅡ级72例(CINⅡ组)、CINⅢ级50例(CINⅢ组)]为研究对象。比较各组患者血清巨噬细胞集落剌激因子(M-CSF)、可溶性肿瘤坏死因子受体Ⅰ(sTNFRⅠ)水平,分析各指标与CIN分级及宫颈癌病理特征的关系,判断各指标对CIN及宫颈癌的诊断价值。结果:各组患者血清M-CSF、sTNFRⅠ水平比较:CINⅠ组<CINⅡ组<CINⅢ组<宫颈癌组,差异均有统计学意义(P<0.05)。CIN患者血清M-CSF、sTNFRⅠ水平与CIN分级呈正相关(P<0.05)。宫颈癌患者血清M-CSF、sTNFRⅠ水平随FIGO分期的升高而升高;肿瘤低、中分化患者血清M-CSF、sTNFRⅠ水平高于肿瘤高分化患者;存在淋巴结转移患者血清M-CSF、sTNFRⅠ水平高于未出现淋巴结转移患者(P<0.05)。血清M-CSF、sTNFRⅠ水平联合检测鉴别CIN及宫颈癌的曲线下面积(AUC)大于各指标单独检测(P<0.05)。血清M-CSF、sTNFRⅠ水平升高是影响CIN进展为宫颈癌的危险因素(P<0.05)。结论:宫颈癌患者血清M-CSF、sTNFRⅠ高于CIN患者,血清指标联合检测对宫颈癌及CIN具有鉴别价值,且各指标变化与宫颈癌病理特征有关。

Regulatory effects of lipopolysaccharide in murine macrophage proliferation

AIMS To study the regulatory effects of bacterial lipopolysaccharide (LPS) in murine macrophage proliferation . METHODS Using murine peritoneal exudate macrophage (PEM) and macrophage cell line J 774 A.1 as targets, LPS effects on M CSF and granulocyte macrophage colony stimulating factor (GM CSF) stimulated macrophage colony forming cells (CFU M) were detected. 125 I GM CSF receptor binding assay was used to examine LPS regulation on GM CSF receptor expression. RT PCR was employed to test TGF β 1 inhibition on IFN γ mRNA expression on macrophage induced by LPS. RESULTS Without direct effect on macrophage proliferation, LPS could inhibit the macrophage proliferation stimulated by GM CSF. However, with the concomitant existence of GM CSF and TGF β 1, the LPS inhibitory effect was eliminated. RT PCR analysis indicated that the strongest macrophage growth inhibitory factor IFN γ mRNA expression in macrophage induced by LPS was remarkably suppressed by TGF β 1, 125 I GM CSF receptor binding assay showed that LPS could enhance GM CSF receptor expression likewise as TGF β 1 . CONCLUSIONS LPS is involved in the network of macrophage proliferative regulation by multiple cytokines, displaying inhibitory and stimulatory effects based on the coexisting cytokines.