Granulocyte-macrophage colony-stimulating factor （GM-CSF） and T-cell responses： what we do and don＇t know

Granulocyte 巨噬细胞刺激殖民地的因素(GM-CSF ) 是一个重要造血的生长因素和有免疫力的调节的人。GM-CSF 也在各种各样的传播白血球的功能的活动有深刻效果。它被许多房间类型在收到有免疫力的刺激之上包括 T 房间，巨噬细胞， endothelial 房间和成纤维细胞生产。尽管 GM-CSF 局部地被生产，它能以一种 paracrine 方式行动到在主人防卫提高他们的功能的成员传播 neutrophils，单核白血球和淋巴细胞。最近的集中的调查为它增加树枝状的房间(DC ) 成熟和功能以及巨噬细胞活动的能力作为一个有免疫力的助手在 GM-CSF 的应用程序上被集中。在经历化疗的癌症病人对待嗜中性白血球减少症临床上被使用，在在治疗期间的爱滋病病人，并且在在骨髓移植以后的病人。有趣地， GM-CSF-deficient 老鼠的造血的系统看起来正常；最重要的变化在一些特定的 T 房间回答。尽管 GM-CSF 的分子的克隆用 T 房间的 cDNA 图书馆被执行， T 房间在激活以后生产 GM-CSF，是众所周知的，在 T 房间功能上有在由 T 房间和它的效果的生产的这 cytokine 的系统的调查的缺乏。在这篇文章，我们将在 T 房间主要集中于 GM-CSF 的免疫生物学。

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.

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.

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 improves cardiac function in rabbits following myocardial infarction

Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.

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.

Mobilization of Peripheral Blood Stem Cells Using Regimen Combining Docetaxel with Granulocyte Colony-stimulating Factor in Breast Cancer Patients

Objective：To evaluate the effectiveness and safety of the mobilization of peripheral blood hematopoietic stem cells by combining docetaxel with granulocyte colony-stimulating factor（G-CSF） in breast cancer patients.Methods：A total of 57 breast cancer patients were treated with docetaxel 120 mg/m2.When the white blood cell（WBC） count decreased to 1.0×109/L,patients were given G-CSF 5-g/kg daily by subcutaneous injection until the end of apheresis.Peripheral blood mononuclear cells（MNC） were isolated by Cobe Spectra Apheresis System.The percentage of CD34＋ cell was assayed by flow cytometry.Results：At a median 6 of days（range 3-8） after the administration of docetaxel,the median WBC count decreased to 1.08×109/L（range 0.20-2.31）.The median duration of G-CSF mobilization was 3 days（range 2-7）.The MNC collection was conducted 8-12 days（median 10 days） after docetaxel treatment.The median MNC was 5.35×108/kg（range 0.59-14.07）,the median CD34＋ cell count was 2.43×106/kg（range 0.16-16.69）.The CD34＋ cell count was higher than 1.00×106/kg in 47 of 57 cases（82.46%） and higher than 2.00×106/kg in 36 cases（63.16%）.The CD34＋ cell count was higher than 2.00×106/kg in 27 collections（23.68%）.The MNC count and the CD34＋ cell count were correlated with the bottom of WBC after docetaxel chemotherapy（r=0.364,0.502,P=0.005,0.000）.The CD34＋ cell count was correlated with the MNC count（r=0.597,P=0.000）.The mobilization and apheresis were well tolerated in all patients.Mild perioral numbness and numbness of hand or feet were observed in 3 cases.No serious adverse events were reported.Conclusion：Mobilization of peripheral blood hematopoietic stem cell by combining docetaxel with G-CSF was effective and safety in breast cancer patients.

Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin against Lung Cancer by Promoting Angiogenesis

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

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。

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。

rhGM⁃CSF预防非小细胞肺癌放疗所致急性放射性食管炎的效果观察

目的探讨注射用重组人粒细胞⁃巨噬细胞集落刺激因子(rhGM⁃CSF)预防非小细胞肺癌(NSCLC)放疗所致急性放射性食管炎的效果。方法选取2016年6月至2020年10月医院收治的168例拟接受放疗的NSCLC患者为研究对象,以随机数字表法分为对照组(n=84)和研究组(n=84)。对照组采用三维适形放疗联合化疗进行治疗,研究组在对照组的基础上采用rhGM⁃CSF治疗,2组均治疗2~6个周期。比较2组治疗前后免疫功能、生活质量核心问卷(QLQ⁃C30)评分,比较2组治疗后放射性食管炎发生情况以及放射性食管炎视觉模拟量表(VAS)评分。结果治疗后,2组CD4+、CD3+、CD16+CD56+水平均升高(P<0.05),研究组高于对照组(P<0.05);治疗后,2组放射性食管炎分级等级差异有统计学意义(P<0.05),且研究组3~4级放射性食管炎发生率低于对照组(P<0.05);2组放射性食管炎患者VAS评分均降低(P<0.05),研究组放射性食管炎患者VAS评分低于对照组(P<0.05);2组QLQ⁃C30评分均降低(P<0.05),研究组低于对照组(P<0.05)。结论rhGM⁃CSF联合三维适形放疗用于治疗NSCLC患者,可改善患者的免疫功能,提高患者的生活质量,减少3~4级放射性食管炎发生率,减轻NSCLC患者经三维适形放疗所致放射性食管炎患者疼痛。

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。