1.Down-regulation of FTO in human gastric cancer and its effect on cell line MGC-803 function
Jingnan PI ; Jie ZHANG ; Xuepeng WANG ; Jiachao XIONG ; Jia YU
Basic & Clinical Medicine 2017;37(7):907-911
Objective To investigate the expression of FTO in gastric cancer tissues and the functional significance of FTO in MGC-803 cell line.Methods The FTO mRNA was detected by RT-qPCR in 54 cases of gastric cancer samples and their paired adjacent normal control tissues.The effect of FTO overexpression in MGC-803 on cell proliferation,cell migration and invasion were detected by CCK-8,wound heal and ranswell assays,respectively.Results The expression of FTO mRNA was significantly lower than that of adjacent tissues(P<O.05).Furthermore,overexpression of FTO in MGC-803 cells inhibited cell proliferation,cell migration and invasion.Conclusions FTO is low expressed in gastric cancer tissues and inhibits gastric cancer cell line MGC-803 proliferation,migration and invasion.FTO is closely associated with the development of gastric cancer.
2.Correlation between dynamic high-density lipoprotein trajectories and clinical outcomes in critically ill children
Jianlei FU ; Xuepeng ZHANG ; Geng ZHANG ; Huaiyu XIONG ; Yi JI ; Siyuan CHEN
Chinese Journal of Applied Clinical Pediatrics 2024;39(3):161-169
Objective:To characterize the longitudinal and dynamic high-density lipoprotein (HDL) trajectories in critically ill children and explore their correlation with clinical outcomes.Methods:Retrospective cohort study.All critically ill children admitted to the Pediatric Intensive Care Unit (PICU) of West China Hospital, Sichuan University from January 1, 2015 to October 1, 2020 were included in this retrospective study.Group-based trajectory modeling (GBTM) was applied to characterize the HDL trajectories in days 0-6 post-PICU admission and develop HDL trajectory groups.The in-hospital mortality rate was reported as frequency (%) and then compared by the Chi-square test or Fisher′s exact test between HDL trajectory groups.The length of stay (LOS) in the PICU was described by M( Q1, Q3), and its difference between HDL trajectory groups was evaluated by the Kruskal Wallis test.Logistic regression and multiple linear regression were used to determine the correlation between HDL trajectories and clinical outcomes.The primary outcome was in-hospital mortality rate, and the secondary outcome was LOS in the PICU. Results:A total of 4 384 critically ill children were ultimately enrolled in the study, and 6 HDL trajectory groups were developed based on GBTM analyses: group 1 (758 cases), the lowest HDL group; group 2 (1 413 cases), the low HDL group; group 3 (74 cases), the low-to-high HDL group; group 4 (621 cases), the medium HDL group; group 5 (1 371 cases), the high HDL group; and group 6 (147 cases), the highest HDL group.Logistic regression analysis showed that compared with critically ill children in group 1, those belonging to groups 2, 3, 4, 5, and 6 were at lower risks of in-hospital mortality with odds ratio ( OR): 0.475, 95%confidence interval ( CI): 0.352-0.641, P<0.001; OR: 0.093, 95% CI: 0.013-0.679, P=0.019; OR: 0.322, 95% CI: 0.208-0.479, P<0.001; OR: 0.263, 95% CI: 0.185-0.374, P<0.001, and OR: 0.142, 95% CI: 0.044-0.454, P=0.001, respectively.Multiple linear regression analysis revealed that compared with critically ill children in group 1, those belonging to groups 4, 5, and 6 had the trend of shorter LOS in PICU, and the β value and 95% CI were β: -4.332, 95% CI: -5.238- -3.426, P<0.001; β: -3.053, 95% CI: -3.809--2.297, P<0.001; β: -6.281, 95% CI: -7.842--4.721, P<0.001, respectively. Conclusions:The dynamic HDL trajectories during 0-6 days after PICU admission are associated with in-hospital mortality rate of critically ill children.The HDL trajectory at a persistently low level is associated with higher mortality, while the HDL trajectory at a persistently high level or with the trend from a low level rising to a high level shows a lower risk of mortality.It is suggested that the HDL trajectory model may become an indicator to predict the condition and prognosis of critically ill children.
3.Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion.
Qiuyun FU ; Xingchi LIU ; Houfu XIA ; Yicun LI ; Zili YU ; Bing LIU ; Xuepeng XIONG ; Gang CHEN
International Journal of Oral Science 2022;14(1):47-47
Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8+ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism*
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CD8-Positive T-Lymphocytes/pathology*
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Carcinoma, Adenoid Cystic/pathology*
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Carcinoma, Squamous Cell/pathology*
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Cell Line, Tumor
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Humans
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Immunosuppression Therapy
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Interferon-gamma/pharmacology*
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Mouth Neoplasms/metabolism*
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Programmed Cell Death 1 Receptor/metabolism*
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Salivary Gland Neoplasms/pathology*