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.

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.

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.

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.

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.

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.

基于CT征象和血清巨噬细胞集落刺激因子、β-连环蛋白构建的联合模型对孤立性肺结节的评估价值

目的探讨基于CT征象和血清巨噬细胞集落刺激因子(M-CSF)、β-连环蛋白(β-Catenin)构建的联合模型对孤立性肺结节的评估价值。方法选取2020年2月至2023年2月萍乡市人民医院病理结果显示孤立性肺结节的105例患者作为研究对象,以孤立性肺结节性质为结局指标,软件计算建模组所需样本量为75例,故随机抽取75例作为建模组、其余30例作为验证组,分析建模组孤立性肺结节不同性质患者一般资料、CT征象、生化指标,多因素logistic回归分析法筛选影响孤立性肺结节性质的独立影响因子,并建立预测模型。用验证组临床资料进行验证并将验证组临床资料代入预测模型,根据预测概率绘制ROC曲线评估该预测模型的效能。结果建模组75例病例中,良性肺结节43例(57.33%)、恶性肺结节32例(42.67)。单因素分析结果显示,良性、恶性肺结节患者毛刺征、分叶征、血管集束征、胸膜凹陷征、磨玻璃密度、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、癌胚抗原(CEA)、神经特异性烯醇化酶(NSE)、M-CSF、β-Catenin水平与建模组孤立性肺结节性质有关,差异有统计学意义(P<0.05)。多因素logistic回归分析显示:毛刺征(β=1.572,OR=1.612,95%CI=1.475~2.159)、分叶征(β=1.484,OR=1.650,95%CI=1.408~2.184)、血管集束征(β=1.292,OR=1.674,95%CI=1.466~2.198)、磨玻璃密度(β=1.307,OR=1.785,95%CI=1.501~2.263)、CEA(β=0.915,OR=1.797,95%CI=1.505~2.199)、NSE(β=0.920,OR=1.824,95%CI=1.618~2.218)、M-CSF(β=0.859,OR=1.765,95%CI=1.506~2.301)、β-Catenin(β=0.867,OR=1.806,95%CI=1.542~2.325)是影响建模组孤立性肺结节性质的独立危险因素(P<0.05),据此建立的联合模型ROC曲线结果显示:该模型评估孤立性肺结节良恶性的灵敏度为90.50%、特异度为75.26%、AUC为0.880(95%CI=0.802~0.935)、阳性似然比为4.05、阴性似然比为0.12、阳性预测值为82.80%、阴性预测值为89.90%。结论毛刺征、分叶征、血管集束征、磨玻璃密度及CEA、NSE、M-CSF、β-Catenin水平升高是影响孤立性肺结节良恶性的独立影响因素,据此构建的联合模型评估孤立性肺结节良恶性的效能较高。

rhG-CSF在治疗儿童化疗性口腔黏膜炎中的应用研究

目的探究重组人粒细胞集落刺激因子(recombinant human granulocyte-colony stimulating factor,rhG-CSF)在治疗儿童化疗性口腔黏膜炎中的应用效果。方法选取2020年1月至2022年6月于笔者医院肿瘤外科化疗的60例化疗性口腔黏膜炎患儿,按随机数字表法分为两组,每组30例。对照组采取生理盐水口腔护理,实验组采取rhG-CSF口腔护理。比较两组患儿干预效果、口腔黏膜炎分度、生存质量[健康状况调查简表(36-item short—form,SF-36)]、患儿家长护理满意度。结果实验组总有效率较对照组高,差异有统计学意义(P<0.05)。干预5d,实验组患儿口腔黏膜炎分度结果优于对照组,差异有统计学意义(P<0.05)。干预5d,两组患儿SF-36评分较干预前高,实验组较对照组高,差异有统计学意义(P<0.05)。实验组患儿家长满意度较对照组高,差异有统计学意义(P<0.05)。结论rhG-CSF口腔护理可有效提高儿童化疗性口腔黏膜炎的干预效果,减轻口腔黏膜炎分度,改善患儿生存质量,提高患儿家长护理满意度。

血管瘤患儿血清粒细胞-巨噬细胞集落刺激因子及转录激活因子3水平与瘤体增生的相关性

目的探索血管瘤患儿血清粒细胞-巨噬细胞集落刺激因子(GM-CSF)及转录激活因子3(STAT3)的表达水平并分析其与瘤体增生的相关性。方法选取2020年1月—2023年1月收治的152例血管瘤增生患儿作为研究对象,分为增生期组(87例)与退化期组(65例),另选择同期确诊为血管畸形的53例患儿作为血管畸形组。对血清GM-CSF、STAT3及碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)、血管生成素-1(Ang-1)的表达水平进行检测;Pearson法相关性分析血清GM-CSF、STAT3与bFGF、VEGF、HIF-1α、Ang-1的相关性;受试者工作特征(ROC)曲线分析血清GM-CSF、STAT3对血管瘤瘤体增生的预测价值;多因素Logistic回归分析血管瘤瘤体增生的影响因素。结果增生期组患儿血清bFGF、VEGF、HIF-1α、GM-CSF、STAT3表达水平高于血管畸形组及退化期组患儿(P<0.05),但血清Ang-1表达水平低于血管畸形组及退化期组患儿(P<0.05);Pearson法相关性分析显示,增生期组患儿血清GM-CSF及STAT3水平均与bFGF、VEGF、HIF-1α水平正相关,与Ang-1水平负相关;ROC曲线下面积显示,GM-CSF和STAT3单独预测血管瘤瘤体增生风险的AUC分别为0.847,0.822,联合预测的AUC为0.918,联合预测的效能显著大于GM-CSF单独诊断的AUC(Z=2.459,P=0.014),STAT3单独诊断的AUC(Z=3.371,P=0.001)。多因素Logistic回归分析显示GM-CSF、STAT3是血管瘤瘤体增生的影响因素(P<0.05)。结论血管瘤瘤体增生患儿血清GM-CSF及STAT3表达水平升高,是瘤体增生的影响因素,联合检测能较好的预测血管瘤瘤体增生风险。

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．

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。

巨噬细胞集落刺激因子-1及其受体在牙周炎中的研究进展

牙周炎是一种影响牙齿周围支持组织的慢性炎症性疾病。牙周组织损伤主要由宿主的免疫反应介导,而目前临床治疗牙周炎主要以局部机械清除菌斑和结石为主,免疫疗法在牙周临床中应用很少。因此,对牙周炎免疫治疗的研究就显得极其重要。巨噬细胞参与宿主免疫反应的关键环节,通过识别、吞噬和清除外来病原体和异物在牙周炎的发生、发展过程中发挥重要作用。研究表明,这一过程是通过巨噬细胞集落刺激因子-1(colony stimulation factor-1,CSF-1)/巨噬细胞集落刺激因子-1受体(colony stimulation factor-1 receptor, CSF-lR)信号轴介导的巨噬细胞炎性调控、破骨细胞骨吸收调控进行的。本综述将CSF-1/CSF-1R信号轴在牙周炎中的作用及其作用机制进行总结,以期为后续研究及牙周炎的免疫治疗提供依据。

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。

干扰素调节因子5、粒细胞-巨噬细胞集落刺激因子在细菌性肺炎病儿血清中的表达及预后价值

目的探讨干扰素调节因子5(interferon regulatory factor 5,IRF5)、粒细胞-巨噬细胞集落刺激因子(granulocyte-macro-phage colony-stimulating factor,GM-CSF)在细菌性肺炎病儿血清中的表达变化及疾病预后价值。方法选取2019年4月至2021年5月中国人民解放军联勤保障部队第九二八医院收治的细菌感染性肺炎病儿96例作为细菌组,同期非细菌感染性肺炎病儿88例作为非细菌组,另外选取健康体检儿童96例为对照组,收集检测三组病儿基本临床资料。检测血清中IRF5、GM-CSF及其组间差异;采用Pearson法分析细菌性肺炎病儿血清IRF5、GM-CSF水平与病情指标的相关性;应用受试者操作特征曲线(ROC曲线)分析IRF5、GM-CSF及二者联合预测细菌性肺炎预后的价值。结果细菌组血清IRF5水平[(38.85±13.86)ng/L]显著高于非细菌组[(11.15±4.37)ng/L]和对照组[(10.76±1.55)ng/L],且重症组高于轻症组(P<0.05);细菌组血清GM-CSF水平[(54.73±16.56)ng/L]显著低于非细菌组[(246.73±28.94)ng/L]和对照组[(250.64±55.67)ng/L],且重症组低于轻症组(P<0.05)。重症组气促、吐沫、三凹征、肺部明显湿啰音比例、C反应蛋白(C-reactive protein,CRP)、白细胞水平显著高于轻症组、非细菌组(P<0.05),轻症组、非细菌组CRP水平显著高于对照组(P<0.05),非细菌组CRP水平显著高于对照组(P<0.05)。血清IRF5水平与CRP、白细胞、临床肺部感染评分(clinical pulmonary infection score,CPIS)均呈正相关(r=0.34、0.36、0.41,P<0.05),血清GM-CSF水平与CRP、白细胞、CPIS均呈负相关(r=-0.40、-0.32、-0.45,P<0.05)。预后不良组血清IRF5水平高于预后良好组,血清GM-CSF水平低于预后良好组(P<0.05)。ROC曲线显示,IRF5、GM-CSF对预后预测的AUC分别为0.90、0.87,二者联合对预后预测的AUC为0.96,明显高于二者单独诊断,(Z联合vs.IRF5=2.86,P=0.004;Z联合vs.GM-CSF=2.24,P=0.025),其灵敏度、特异度分别为90.32%、90.77%。结论细菌性肺炎病儿血清IRF5水平升高,GM-CSF水平降低,二者在评估病情进展及疾病预后预测方面具有较高的价值。