1.Enhanced Cell Surviving against Oxidative Stress and Treg-inducing Ability of Dedifferentiated Human Umbilical Cord Mesenchymal Stem Cells Modified by IDO Gene
Mei-na KUANG ; Si-rui HUANG ; Xin LU ; Chang ZHOU ; Yao-hua HU ; Zhen-lin TANG ; Yin YUAN
Journal of Sun Yat-sen University(Medical Sciences) 2019;40(2):187-194
【Objective】 To investigate whether the dedifferented human umbilical cord mesenchymal stem cells(hMSC)modified by IDO gene can get improved ability to survive oxidative stress as well as to induce regulatory T(Treg) lymphocytes.【Methods】The dedifferentiated hMSC(De- hMSC)were obtained by a transient adipogenic induction and subsequent recovery culture in normal medium. The IDO gene modified De-hMSC (IDO/De-hMSC)were prepared by retroviral infection using recombinant retrovirus harboring IDO gene. The De- hMSC infected by retrovirus containing ZsGreen1 gene,the non- infected De- hMSC and hMSC were set as controls. Exogenous expression of IDO protein was confirmed by Western blot. Flow cytometry analysis was performed to detect the immunophenotype of IDO/De- hMSC , and their osteogenic/adipogenic differentiation abilities were also assessed. Cell survival rates under the oxidative stress of 300 μmol/L t- BHP were determined by Annexin V- FITC/PI double staining flow cytometry. Human peripheral blood mononuclear cells (PBMC) were isolated and treated with conditioned medium containing the culture supernatant of hMSC,De-hMSC,Mock/De-hMSC and IDO/De-hMSC,respectively. Changes in the proportion of CD4+ CD25+ CD127low Treg cells in PBMC were determined by triple fluorescent labeling flow cytometry.【Results】The De-hMSC modified by IDO gene still have the immunophenotype as well as the osteogenic/adipogenic differentiation abilities that are typical of mesenchymal stem cells. When challenged by 300 μmol/L t-BHP,the number of viable cells in De-hMSC significantly elevated compared with hMSC(P<0.05),and the survival advantage of De-hMSC was not obviously affected by IDO gene modification(P>0.05). Conditioned medium containing the supernatant from IDO/De- hMSC dramatically up- regulated the percentage of CD4+CD25+CD127low Treg cells in PBMC in contrast to the control groups(P<0.05).【Conclusions】IDO/ De- hMSC have the same immunophenotype and differentiation capacity as the native hMSC ,and can simultaneously enhance the ability of hMSC to survive against oxidative stress and to induce Treg cells ,which may be a potential modification strategy of mesenchymal stem cells for immunosuppressive therapy.
2. Analysis of mortality trend and related factors for aged in-patients with diabetes mellitus
Li-na ZHANG ; Yu-qiong WEN ; Xiao-ying FU ; Jin-xin LIN ; Shui-qing LAI ; Hong-mei CHEN ; Si-min LIU ; Jian KUANG
Chinese Journal of Practical Internal Medicine 2019;39(09):809-812
OBJECTIVE: To find out the mortality trend and related factors in aged hospitalized patients with diabetes mellitus(DM). METHODS: The case information diabetic in patients who died during the period from 2005 to 2014 were collected and the mortality and causes of death were analyzed. RESULTS: From 2005 to 2014, 1297 diabetic patients died, and the mortality of elderly DM inpatients was 4.44%(1162 cases), significantly higher than that of the non-elderly of 0.94%(P<0.001). The death rate of elderly diabetic patients was significantly higher in males than in females(5.22% vs. 3.47%, P<0.001). The mortality of the aged diabetic patients decreased within 10 years(P<0.001), decreasing from 4.75% in 2005 to 3.01% in 2009(P<0.001) in the year of 2005-2009, while there were no differences in the year of 2010-2014. The main death causes of the aged diabetic in-patients were as follows: infections(27.71%), cardiovascular diseases(25.22%), tumor(21.34%), cerebral vascular diseases(10.41%) and diabetic complications(5.51%). The first death cause in the 60-79 yrs group was cardiovascular diseases, while in the ≥80 yrs group, it was infections. The constituent ratio of infection as death cause in the aged during 2010-2014 significantly increased(22.60% vs. 32.50%, P<0.001), increasing by 43.81%, and it became the first cause of death in 2010. CONCLUSION: The death rate of the elderly DM in-patients has decreased significantly within 10 years, from 2005 to 2014, while the rate has kept steady from 2010. Infections and cardiovascular diseases are the main cause of death. So it's important to prevent the elderly hospitalized DM patients from infection, in addition to cardiovascular diseases, and to control in time.
3.Clinical and genetic characteristics of young patients with myeloproliferative neoplasms
Mengyu ZHANG ; Mei BAO ; Dayu SHI ; Hongxia SHI ; Xiaoli LIU ; Na XU ; Minghui DUAN ; Junling ZHUANG ; Xin DU ; Ling QIN ; Wuhan HUI ; Rong LIANG ; Meifang WANG ; Ye CHEN ; Dongyun LI ; Wei YANG ; Gusheng TANG ; Weihua ZHANG ; Xia KUANG ; Wei SU ; Yanqiu HAN ; Limei CHEN ; Jihong XU ; Zhuogang LIU ; Jian HUANG ; Chunting ZHAO ; Hongyan TONG ; Jianda HU ; Chunyan CHEN ; Xiequn CHEN ; Zhijian XIAO ; Qian JIANG
Chinese Journal of Hematology 2023;44(3):193-201
Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.