1.Therapeutic effects of B and T lymphocyte attenuator extracellular domain and heat shock protein 70 antigen peptide on cervical cancer in mouse model
Lingfei HAN ; Weimin QIU ; Cheng HU ; Ling WANG ; Hongxia YAO ; Shiyi XIONG ; Meng MENG ; Yong FANG ; Ding MA
Chinese Journal of Obstetrics and Gynecology 2010;45(8):603-608
Objective To investigate the synergistic therapy effects of B and T lymphocyte attenuator(BTLA) extracellular domain in combination with heat shock protein 70 (HSP70)-TC-1 antigen peptide complex on the mouse model of cervical cancer and the related immunological mechanisms. Methods(1)Detecting the BTLA and herpesvirus entry mediator (HVEM) gene expression in the tumor microenvironment after C57BL/6 mice were inoculated with TC-1 tumor cells by realtime PCR; BTLA,HVEM expression on tumor infiltrating lymphocytes cell surface were detected by flow cytometry (fluorescence intensity). (2) According to different treatments, tumor-bearing mice were divided into 5 groups, which was injected with pcDNA3. 1 (empty vector plasmid as control), psBTLA (vector plasmid which expresses BTLA extracellular domain), HSP70 (HSP70-TC-1 cell peptide complex), HSP70 +pcDNA3.1 or HSP70 + psBTLA, respectively. The weight of tumor was recorded. The expression of immunoregulatory genes in tumor microenvironment were detected. The change of lymphocyte amount and cytotoxicity were detected too; lymphocyte proliferation activity was measured by tritium thymidine incorporation assay; the concentration of interleukin (IL) 2 and interferon-γ(IFN-γ) in supernatants of spleen lymphocyte were measured by enzyme-linked immunosorbent assay (ELISA). Results (1) BTLA gene expression was gradually increased after tumor cells inoculation. The highest expression level was 2. 83 + 0. 35 at 14th day, which had statistical significance difference with the 7th day expression of 1.66±0. 25 (P < 0. 05). While HVEM mRNA expression did not change significantly (P > 0. 05). The 7th and 14th day after TC-1 cells inoculation, the average fluorescence intensity of BTLA expression on the surface of tumor infiltrating lymphocytes was 33.5 and 51.8, respectively, in which there was statistically significant difference (P <0. 05); while the difference of HVEM expression was not statistically significant (57. 2 vs 49. 3 ,P >0. 05). (2)The 28th day after inoculation, tumor inhibition rate of HSP70 + psBTLA group was 88%, which was significantly higher than other treatment groups (P <0. 05). The 28th day after TC-1 cells inoculation, combination therapy not only promoted IFN-γ and IL-2 gene (3. 12 + 0.71,3.20 + 0. 62)expression but also reduced transforming growth factor-β (TGF-β), Foxp3 and IL-10 expression (0. 25±0. 03,0. 19 +0. 03,0. 31 +0. 04;P <0. 05). It also promoted CD8+ T lymphocyte infiltration(52 +6)/high power field, cytotoxicity (65.5±2.4) %, proliferation (15.0 × 103 cpm) and cytokine IL-2 , IFN-γsecretion(824±51), (1096±112) pg/ml, which were all significantly higher than other groups (P <0. 05). Conclusion The effect of immunotherapy on tumor can be augmented by the combination of psBTLA which expresses extracellular domain of BTLA and HSP70-TC-1 tumor antigen peptide complex,which could improve the expression of the related immunoregulatory genes to establish a much better microenvironment in favor of anti-tumor immune response against the mice model of the cervix carcinoma.
2.Analysis of risk factors associated with acute Stanford type B aortic dissection complicated with pleural effusion and observation of the curative effect after intracavitary repair
Lingfei ZHENG ; Dujuan MENG ; Yasong WANG ; Tienan ZHOU ; Xiaozeng WANG
Chinese Journal of Internal Medicine 2023;62(8):964-971
Objective:To investigate the risk factors of acute Stanford type B aortic dissection (TBAD) complicated with pleural effusion (PE) and the short-term and long-term outcomes of thoracic endovascular aortic repair (TEVAR).Methods:A case-control study. The clinical and imaging data of 1 083 patients with acute TBAD admitted to the General Hospital of Northern Theater Command from April 2002 to December 2020 were retrospectively analyzed, including 211 cases with pleural effusion and 872 cases without pleural effusion. The baseline analysis of the two groups of patients was performed. The risk factors associated with pleural effusion were analyzed by binary logistic regression, and the results were expressed as odds ratio ( OR) and 95% confidence interval ( CI). According to the quantity of pleural effusion, they were simultaneously divided into small pleural effusion group and medium large pleural effusion group, to compare the short-term and long-term effects of TEVAR patients with different amounts of pleural effusion. Results:The incidence of pericardial effusion (17.5% vs. 3.8%, P<0.001), anemia (21.3% vs. 12.5%, P=0.001), aortic spiral tear (49.8% vs. 37.8%, P=0.002), dissection tear over diaphragm (57.8% vs. 48.1%, P=0.011), serum creatinine [85 (69, 111) vs. 81 (67, 100) μmol/L, P=0.011] and white blood cell levels[(11.3±4.2)×10 9/L vs. (10.3±4.2)×10 9/L, P=0.002] in acute TBAD pleural effusion group were significantly higher than those in non-pleural effusion group, and the hemoglobin level was significantly lower than that in non-pleural effusion group [(128±20) vs. (133±17) g/L, P<0.05]. Logistic stepwise regression analysis showed that pericardial effusion ( OR=5.038,95% CI 2.962-8.568, P<0.001), anemia ( OR=2.047,95% CI 1.361-3.079, P=0.001), spiral tear ( OR=1.551,95% CI 1.030-2.336 , P=0.002) and elevated white blood cell ( OR=1.059,95% CI 1.011-1.102, P=0.005) were independent risk factors for TBAD complicated with pleural effusion. The incidences of all-cause death (4/19 vs. 1.5% vs. 0.9%, P<0.001), aortogenic death (4/19 vs. 0.7% vs. 0.7%, P<0.001) and aortic related adverse events (4/19 vs. 1.5% vs. 1.1%, P<0.001) in patients with large pleural effusion during TEVAR operation were significantly higher than those in patients with small pleural effusion and those without pleural effusion, and the differences were statistically significant. At 1 month follow-up after TEVAR, the incidence of all-cause death (4/16 vs. 3.3% vs. 1.6%, P<0.001), aortogenic death (4/16 vs. 0.8% vs.0.7%, P<0.001), aorta related adverse events (4/16 vs. 4.1% vs. 4.7%, P=0.013) and overall clinical adverse events (4/16 vs.9.8% vs. 6.7%, P=0.014) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. At 1 year follow-up after TEVAR, the incidence of all-cause death (4/15 vs. 4.9% vs. 3.9%, P=0.004), aortogenic death (4/15 vs.2.5% vs. 2.1%, P<0.001), aorta related adverse events (5/15 vs. 11.5% vs. 9.4%, P=0.012) and overall clinical adverse events (5/15 vs. 18.9% vs. 13.1%, P=0.029) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. Conclusions:Single center data showed that pericardial effusion, anemia, spiral tear and elevated white blood cell were independent risk factors for acute TBAD complicated with pleural effusion; the early (1 month) and long-term (1 year) rates of all-cause death, aortic mortality, aortic adverse events and overall clinical adverse events were significantly higher in TBAD patients with moderate pleural effusion after TEVAR, and moderate and large pleural effusion was an independent risk factor for near and long-term aortic related adverse events after TEVAR surgery.
3.Risk factors for the occurrence and treatment failure of peritoneal dialysis-associated E. coli peritonitis
Siyu CHENG ; Liming YANG ; Xueyan ZHU ; Xiaoxuan ZHANG ; Lingfei MENG ; Shizheng GUO ; Xiaohua ZHUANG ; Xiaoying BAI ; Ping LUO ; Wenpeng CUI
Chinese Journal of Clinical Infectious Diseases 2021;14(3):173-178
Objective:To investigate the clinical characteristics of E. coli peritoneal dialysis-associated peritonitis (PDAP) and the risk factors for its occurrence and treatment failure.Methods:The clinical data of patients with episodes of PDAP in four general hospitals in Jilin Province from 2013 to 2019 were retrospectively reviewed. According to the pathogenic bacteria, the patients were divided into E. coli and non- E. coli groups. The incidence of E. coli PDAP in the last seven years was calculated and the clinical characteristics were compared between two PDAP groups. Logistic regression was used to analyze the risk factors for the occurrence and treatment failure of E. coli PDAP. Results:A total of 693 PDAP episodes/cases were enrolled in this study, including 100 episodes/cases in the E. coli group and 593 episodes/cases in the non- E. coli group. The incidence rate of E. coli PDAP in the four hospitals showed a decreasing trend during 2013 to 2019. Compared with the non-E.coli group, the proportion of diabetic patients and the average blood albumin levels in the E. coli group were lower ( χ2=5.006, Z=-2.992, P<0.05), while the proportion of refractory peritonitis was higher, and the duration of antibiotic therapy was longer ( χ2=6.350, Z=-2.779, P<0.05). Multivariate Logistic regression analysis showed that history of PDAP ( OR=1.577, 95% CI: 1.015-2.448) and low baseline serum albumin level ( OR=0.958, 95% CI: 0.923-0.995) were independent risk factors for the development of E. coli PDAP, while concomitant diabetes was an independent protective factor for E. coli PDAP ( OR=0.538, 95% CI: 0.330-0.876). Moreover, long-term dialysis was an independent risk factor for treatment failure of E. coli PDAP ( OR=1.047, 95% CI: 1.018-1.076). Conclusion:The incidence rate of E. coli PDAP in study institutions has declined in the past 7 years, but the rate of refractory PDAP is still high. The history of PDAP and low blood albumin level are independent risk factors for the occurrence of E. coli PDAP, while concomitant diabetes is an independent protective factor for the occurrence of E. coli PDAP. Long-term dialysis is an independent risk factor for treatment failure of E. coli PDAP.