1.Epidemiological characteristics of newly reported HIV-infected cases aged 50 years and above in Henan province, 1995-2020
Yan LIANG ; Yake XU ; Panying FAN ; Dongyang ZHAO ; Jianchun SHI ; Jiangzhou YAN ; Xiaoyu JI ; Guolong ZHANG
Chinese Journal of Epidemiology 2022;43(12):1912-1919
Objective:To analyze the epidemiological characteristics of newly reported HIV-infected cases aged 50 years and above in Henan province during 1995-2020, and to provide evidence for strategies on HIV/AIDS prevention and control.Methods:Information about newly reported HIV-infected cases aged 50 years and above in Henan between 1995 and 2020 were collected from the National Comprehensive HIV/AIDS Information System. The demographic and behavioral characteristics of HIV-infected cases aged ≥50 were analyzed, and the mixed linear model based on CD4 + T lymphocyte (CD4) counts back calculation was used to estimate the years, time and age of the HIV infection. Results:During 1995-2020, a total of 25 038 HIV-infected cases aged 50 years and above were newly reported, accounting for 25.8% (25 038/96 867) of the total number of newly reported HIV-infected cases in Henan. The proportion of newly reported cases over 50-years-old gradually increased from 4.5% (18/396) in 1995-2000 to 35.5% (9 666/27 239) in 2016-2020, with statistically significant difference ( χ2=3 105.53, P<0.001). Among them, the proportion of HIV-infected cases aged 60 years and above were increasing year by year. The proportion of male cases were increasing along with ageing. The proportion of HIV-infected cases detected by medical institutions also showed an upward trend. The newly reported HIV-infected cases aged 50 years and above were mainly transmitted through sexual contact. The proportion of heterosexual transmission increased from 5.5% (1/18) in 1995-2000 to 86.2% (8 334/9 666) in 2016-2020, and the proportion of MSM-behavior-related transmission increased from 0.0% in 1995-2000 to 13.5% (1 304/9 666) in 2016-2020. The majority of cases had extra-marital and/or non-commercial heterosexual behavior (48.1%, 4 007/8 334) and the proportion showed an upward trend. The majority of male cases had commercial heterosexual behavior (54.9%, 3 169/5 775), and with increasing proportion along with the increase of age. The majority of female cases had extra-marital and/or non-commercial heterosexual behavior (62.5%, 1 600/2 559), with increasing proportion of extra-marital and/or non-commercial heterosexual behavior. The proportion of heterosexual behavior with spouse or stable sexual partners showed a downward trend. The estimations based on CD4 counts back calculation model showed that among the newly reported HIV-infected cases aged 50 years and above, the average age being infected was (54.8±10.2) years, with 33.8% (4 263/12 621) infected before 50. The interval between infection and diagnosis was (5.7±6.2) years, of which 52.6% (6 636/12 621) were infected for 5 years or longer and 34.7% (4 384/12 621) were in the last 3 years. There was no linear correlation trend in the composition of infection years among the newly reported HIV-infected cases over 50-years-old. Conclusions:In Henan, from 1995 to 2020, the number of newly reported HIV-infected cases aged 50 years and above was increasing and sexual transmission becoming the main transmission route. The increase of prevalence was mostly seen in 60-years-old men, low education level and detected mainly by medical institutions. For this age group, the focus of HIV/AIDS prevention and control should target on those who were transmitted through extra-marital and/or non-commercial heterosexual, commercial heterosexual and MSM behavior and it is necessary to strengthen the HIV testing and detection in this population and in the elderly floating group.
2.Optimization study of CAR-T cell expansion targeting CD99
Yixuan WANG ; Miao YU ; Jiaxuan ZHAO ; Fenfang ZHAO ; Yi ZENG ; Youyong WANG ; Haichuan ZHU ; Tongcun ZHANG ; Jiangzhou SHI
China Oncology 2024;34(7):639-649
Background and purpose:Chimeric antigen receptor T(CAR-T)cell therapy has shown remarkable efficacy in treating hematological and lymphatic system tumors,but its effectiveness in solid tumors is relatively poor,which is partly attributed to target selection.For Ewing sarcoma(ES),CD99 can be a potential target for CAR-T cells.However,due to T cells'endogenous expression of CD99 protein,CAR-T cells targeting CD99 face limitations in their expansion capacity in vitro.This study aimed to identify the optimal conditions for preparing CD99 CAR-T cells by incorporating CD99 knockdown short hairpin RNA(shRNA),optimizing the multiplicity of infection(MOI)for lentiviral transduction,and screening for the best culture medium and container for CAR-T cell expansion.Methods:shRNA sequences were screened to enhance the expansion capacity of CD99 CAR-T cells.Different MOI,culture media,and containers were used to assess CAR-T cell transduction efficiency,cell viability,proliferation capacity,specific killing ability,and interferon-γ(IFN-γ)release levels under various conditions,in order to identify the optimal cell preparation conditions.Results:The expansion level of KO-CD99 CAR-T cells obtained through shRNA knockdown was significantly higher than that of CD99 CAR-T cells[(16.40±0.40)vs(6.33±1.53),P<0.01].The optimal expansion effect was observed when the transduction MOI was between 0.25 and 1.0,and OptiVitro was used as the culture medium.CAR-T cells cultured in ventilated flasks exhibited significantly higher expansion rates compared to cells cultured in bags[MOI=0.25:(50.23±3.32)vs(13.02±4.82);MOI=0.50:(49.96±0.83)vs(18.25±2.88);MOI=1.00:(48.27±5.08)vs(13.16±6.26);P<0.01],with better cell phenotype and higher specific killing ability.Conclusion:KO-CD99 CAR-T cells obtained through shRNA technology can achieve stable expansion.Based on the optimization of expansion conditions,KO-CD99 CAR-T cells exhibit superior expansion capacity and a higher proportion of memory T cells when the MOI is between 0.25 and 1.00,OptiVitro is used as the culture medium,and ventilated flasks are used as the culture container.These findings lay a solid foundation for further clinical trials of CD99 CAR-T cell therapy for ES.