Abstract: Objective　To explore the clinical features and survival prognosis of stage Ⅳ non-small cell lung cancer (NSCLC) and provide a reference for prognosis evaluation and prevention and treatment of the disease. Methods A retrospective analysis was performed on 195 patients with stage Ⅳ NSCLC admitted to the Department of Medical Oncology and the Department of Respiratory Medicine of the First Affiliated Hospital of Hainan Medical University from 2016 to 2020, who were diagnosed pathologically and available for the analysis and study. Patients' hospitalization records and follow-up information were collected to analyze the survival of the patients at the cut-off of follow-up. The Kaplan-Meier method was used to calculate survival rates, and the Log-rank method was employed for univariate analysis of factors affecting survival. The risk factors for patients' survival prognosis were analyzed by multivariate Cox regression model. Results The median survival time for patients with stage Ⅳ NSCLC was 17.05 months (95% CI: 12.64-21.45), with cumulative survival rates of 70.7%, 41.5%, and 22.0% at 1, 2, and 3 years, respectively. The results of multivariate analysis suggested that gender (HR=0.697, 95% CI: 0.486-0.999, P=0.049), functional status scale (Karnofsky, KPS) (HR=1.535, 95% CI: 1.038-2.270, P=0.032), computed tomography (CT) tumor location (HR=1.481, 95%CI:1.003-2.186, P=0.036), pathology type (HR=1.181, 95%CI:0.715-1.950, P=0.019), metastatic site (HR=1.710, 95%CI:1.214-2.409, P=0.002), N stage (HR=2.094, 95%CI:0.973-4.509, P=0.006), gene mutation (HR=2.387, 95%CI:1.590-3.584, P<0.001), treatment with chemotherapy-containing regimen (HR=1.713, 95%CI:1.094-2.683, P= 0.019), and combination therapy (HR=1.874, 95%CI:1.253-2.802, P=0.002) were independent prognostic factors affecting the survival of patients with stage Ⅳ NSCLC (all P<0.05). In the subgroup analysis, metastatic site and chemotherapy-containing treatment regimen were independent prognostic factors affecting the survival of mutation-positive patients with stage Ⅳ NSCLC, and patients who received targeted therapy had longer survival time. The metastatic site, chemotherapy-containing treatment regimen, and combination therapy were prognostic factors affecting the survival prognosis of patients with gene mutation-negative stage Ⅳ NSCLC or unknown status. Conclusions In this study, gender, KPS score, CT tumor location, pathologic type, metastatic site, N stage, gene mutation, treatment with chemotherapy-containing regimen, and combination therapy were the important factors affecting the survival prognosis of patients with stage Ⅳ NSCLC. In terms of treatment options, chemotherapy remains an indispensable basic treatment option. Moreover, comprehensive treatment can prolong survival compared to a single treatment option. Patients with positive gene mutations who received targeted drugs had longer survival times; therefore, detecting gene mutation status and selecting corresponding targeted drugs in the treatment of stage Ⅳ NSCLC could extend survival periods.

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly increased in the spleens of mice immunized with cFR1 (P < 0.05). IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies against self-FGFR-1 were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-1-immunized group than in mouse FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P<0.05), and the survival time was significantly longer in cFR-1-immunized group than in the control groups (P<0.01). MVD was significantly lower in cFR-1-immunized group than in mFR-1-immunized group and NS group (16.8+/-5.6 vs 64.6+/-1.8 and 59.6+/-8.7, P<0.01). Antibodies against self-FGFR-1 were found in mFR-1-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-1-immunized group were significantly increased (P<0.01) These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein (AF) vaccine in a mouse H22 hepatoma model, tumor volume and survival rate of the mice were studied at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining, and anti-FGFR1 antibody-producing B cells (APBCs) were tested by enzyme-linked immunospot (ELISPOT) assay. Compared with the three control groups, the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group (P<0.05). The number of APBCs in AF-immunized mice (129.6+/-10.9) was more than in controls [6.2+/-1.1 (FGFR1), 6.0+/-1.2 (Ag43) and 5.2+/-1.4 (NS), P<0.01]. Moreover, the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice, but not in control groups. MVD in AF-immunized group was significantly lower than in FGFR1-immunized group, Ag43-immunized group and NS group (10.3+/-3.1 vs 39.4+/-8.6 vs 42.3+/-9.8 and 43.6+/-10.6, P<0.01). These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.

Objective To understand the distribution of inhaled allergens throughout Hainan province and explore effective preventive measures against allergen by examining the serum allergen of patients with chronic rhinosinusitis (CRS), which will provide evidence for specific immunotherapy for treating CRS. Methods Three hundred and eighteen CRS patients underwent Phadiatop blood test by using the UniCAP 100 , a completely automatic autoanalyser. Allergen-specific IgE of 7 common allergens were tested and the concentration of total immunoglobulin E (TIgE) was collected and evaluated. Results The positive rates of the serum TIgE and inhaled allergens were 64.15% and 37.74% respectively. The incidences of the positive serum SIgE is 33.96%. Among the positive cases, 28.30% of the inhaled allergens were dermatophagoides pteronyssinus, 27.36% for tropical mites, 21.07% for dermatophagoides farinae, 13.52% for cockroach, 11. 64% for house dust, 7. 86% for cat dander and 0.63% for dog dander. The incidences of positive TIgE and SIgE were not significantly different between patients with nasal polyps and sinusitis only. Conclusions Dermatophagoides pteronyssinus, tropical mites and dermatophagoides farinae are the main inhaled allergens for CRS patients in Hainan.

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly increased in the spleens of mice immunized with cFR1 (P＜0.05). IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken (cFR-1) in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. Auto-antibodies against self-FGFR-l were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-l-immunized group than in mouse FGFR-1 (mFR-1) immunized group and normal saline (NS) control group (P＜0.05), and the survival time was significantly longer in cFR-l-immunized group than in the control groups (P＜0.01). MVD was significantly lower in cFR-l-immunized group than in mFR-l-immunized group and NS group (16.8 ±5.6 vs 64.6±1.8and 59.6±8.7, P＜0.01). Antibodies against self-FGFR-1 were found in mFR-l-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-l-immunized group were significantly increased (P＜0.01) These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day interval,Microvessel density(MVD)was detected by immunohistochemistry.The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining,and anti-FGFR1 antibody-producing B cells(APBCs)were tested by enzyme-linked immunospot(ELISPOT)assay.Compared with the three control groups,the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group(P<0.05).The number of APBCs in AF-immunized mice(129.6±10.9)was more than in controls[6.2±1.1(FGFR1),6.0±1.2(Ag43)and 5.2±1.4(NS),P<0.01].Moreover,the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice,but not in control groups.MVD in AF-immunized group was significantly lower than in FGFR1-immunized group,Ag43-immunized group and NS group(10.3±3.1 vs 39.4±8.6 vs 42.3±9.8 and 43.6±10.6,P<0.01).These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.