Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19) / 生物工程学报

Adoptive immunotherapy based on chimeric antigen receptor-modified T cells (CAR-T) is one of the most promising strategies to treat malignant tumors, but its application in solid tumors is still limited. Glypican-3 (GPC3) is a meaningful diagnostic, therapeutic, and prognostic biomarker for hepatocellular carcinoma (HCC). The second/third generation GPC3-targeted CAR-T cells are generated to treat HCC. In order to improve the therapeutic effect, we constructed a fourth-generation lentiviral vector to express GPC3 CAR, human interleukin-7 (IL-7) and CCL19. Then the lentiviral vector and packaging plasmids were co-transfected into HEK293T cells to generate CAR lentiviral particles. Human T lymphocyte cells were transduced with CAR lentiviral to develop the fourth-generation GPC3-targeted CAR-T cells (GPC3-BBZ-7×19). In vitro, we used cell counting, transwell assay, luciferase bioluminescence assay and flow cytometry to compare the proliferation, chemotaxis, cytotoxicity and subtype distribution between GPC3-BBZ-7×19 CAR-T cells and the second generation GPC3-targeted CAR-T cells (GPC3-BBZ). In vivo, we established GPC3-positive HCC xenograft model in immunodeficient mice, then untransduced T cells (non-CAR-T) or GPC3-BBZ-7×19 CAR-T cells were injected. Tumor growth in mice was observed by bioluminescence imaging. Results showed that compared with GPC3-BBZ CAR-T, GPC3-BBZ-7×19 CAR-T cells had stronger proliferation, chemotactic ability, and higher composition of memory stem T cells (Tscm) (P values<0.05). However, there were no significant difference in cytotoxicity and cytokine secretion between them. In addition, GPC3-BBZ-7×19 CAR-T cells could significantly eliminate GPC3-positive HCC xenografts established in immunodeficient mice. Therefore, the fourth-generation GPC3-targeted CAR-T cells (secreting IL-7 and CCL19) are expected to be more durable and effective against HCC and produce tumor-specific memory, to provide a preclinical research basis for future clinical trials.

Survival analysis of people living with HIV/AIDS in Sichuan province, 1991-2017 / 中华流行病学杂志

Objective@#To analyze the survival time of people living with HIV/AIDS and related influencing factors in Sichuan province during 1991-2017.@*Methods@#A retrospective cohort study was conducted to analyze the data of 143 988 HIV/AIDS cases. The data were collected from Chinese HIV/AIDS Comprehensive Information Management System. Life table method was used to calculate the survival proportion of the cases, and Cox proportion hazard regression model was used to identify the factors related with survival time.@*Results@#Among 143 988 HIV/AIDS cases a total of 30 420 cases died of AIDS related diseases (21.1%) and the average survival time was 11.51 years (95%CI: 11.39-11.64). Multivariate Cox regression analysis showed that the influencing factors for the survival of HIV/AIDS cases were gender (male vs. female, HR=1.35, 95%CI: 1.32-1.40), education level (primary school or below vs. junior middle school: HR=1.15, 95%CI: 1.12-1.18), ethnic group (Han vs. other ethnic groups, HR=1.46, 95%CI: 1.41-1.52), occupation (farmer vs. other occupations: HR=1.26, 95%CI: 1.22-1.29), age (≥55 years old vs. 15-24 years old: HR=3.18, 95%CI: 3.02- 3.36), disease phase (AIDS vs. HIV infection: HR=1.44, 95%CI: 1.39-1.48), antiretroviral therapy (ART) (receiving ART vs. receiving no ART: HR=0.20, 95%CI: 0.19-0.20), and CD4+T cell counts at diagnosis (>500 cells/μl vs.<200 cells/μl: HR=0.42, 95%CI: 0.40-0.45).@*Conclusions@#The average survival time of HIV/AIDS cases was 11.51 years in Sichuan during 1991- 2017. The risk factors for the survival of the cases were male, education level of primary school or below, Han ethnic group, farmer, old age at diagnosis, disease phase, The protective factors for the survival of HIV/AIDS cases were receiving ART and higher CD4+ T cell counts at diagnosis.

Survey of patients' recognition and demand for enhanced-CT examination-related knowledge / 现代临床护理

Objective To explore patients' recognition and demand for enhanced-CT examination-related knowledge. Method A self-designed questionnaire was used to investigate the recognition and demands for the knowledge among 295 patients who receiving enhanced-CT examination for the first time. Results The awareness rate of enhanced-CT examination related knowledge was 19.0%~51.5%and the demand rate was 62.4%~87.1%. The routes by which the patients acquired the knowledge included lecturing by medical staff personnel, reading the handouts and watching video. Conclusions The level of patients'recognition about the enhanced-CT examination related knowledge is low, but their demands for it is high. Therefore, the medical personnel should improve patients'awareness of enhanced-CT examination related knowledge in various ways.

The Comparison of Adaptation of Plat-ⅡCastable Ceramic Crowns Made by Three Methods / 中山大学学报(医学科学版)

【Objective】To improve the adaptation of Plat-Ⅱceramic crown.【Method】The Plat-Ⅱcastable ceramic crowns were made by three methods,namely routine method,die spacer technique,and the model investing method.24 crowns were made by these three methods individually and adhered to the corresponding model die with zinc phosphate to measure the adhesive thickness and compare their adaptation.【Result】The average adhesive thickness at different parts of crown of these three groups were 52 μm、42 μm、30 μm and the margins discrepence were 63 μm、59 μm、42 μm,respectively.There is statistically difference in both the adhesive thickness and the margin discrepence with these three methods (P<0.01).【Conclusion】The crowns made from the die spacer technique and the model investing method could improve the adaptation significantly.