OBJECTIVETo establish the ADAR1 (adenosine deaminase that act on RNA 1) knockout MLL-AF9 acute myeloid leukemia (AML) mouse model, and to preliminarily investigate the effects of ADAR1 deletion on the development of AML.

METHODSThe lineage⁻ (Lin⁻) cells of ER-CreADAR1(lox/lox) mice and their ADAR1(lox/lox) counterparts were enriched by magnetic activated cell sorting (MACS) and then transduced with retrovirus carrying MSCV- MLL/AF9-IRES-GFP fusion gene. The efficiency of transduction was detected by flow cytometry, and equal number of GFP⁺ cells were transplanted into lethally irradiated recipient mice. The recipient mice were treated with tamoxifen at 48 hours after transplantation to induce ADAR1 knockout and divided into following groups: experimental group (ER-Cre;ADAR1(lox/lox)+tamoxifen), control groups ((1)ER-Cre;ADAR1(lox/lox)+vechile, (2)ADAR1(lox/lox)+tamoxifen, (3)ADAR1(lox/lox)+vechile). The percentage of GFP⁺ cells in peripheral blood was examined at 10, 15 and 20 days respectively after transplantation and the survival of the recipient mice was observed. In vitro study, ER-Cre;ADAR1(lox/lox) and ADAR1(lox/lox) AML cells were cultured and the apoptosis rates of these cells 48 hours after 4-hydroxytamoxifen treatment were examined.

RESULTSThe ADAR1 deletion MLL-AF9 AML mouse model was successfully established. Deletion of ADAR1 could decrease the percentage of GFP⁺ cells in the peripheral blood and significantly prolong the survival rate of recipient mice（P<0.05）. In vitro study showed that the cultured total cell number, percentage of GFP⁺ cells decreased and the apoptosis rate of AML cells increased.

CONCLUSIONAblation of ADAR1 could delay the progression of AML in recipient mice. ADAR1 plays a critical role in the development and maintenance of murine MLL-AF9 AML.

Adenosine Deaminase ; Animals ; Apoptosis ; Disease Models, Animal ; Leukemia, Myeloid, Acute ; Mice ; Myeloid-Lymphoid Leukemia Protein ; Tamoxifen ; analogs & derivatives

Objective: To analyse the mental state of patients with allergic rhinitis (AR) in Chengdu. Methods: One thousand five hundred and thirty-six AR patients from Sichuan Provincial Integrated Traditional Chinese and Western Medicine Hospital, West China Hospital of Sichuan University, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan People′s Hospital, Sichuan Second Hospital of Traditional Chinese Medicine were selected from July 2013 to January 2018. Eight hundred and twenty-seven patients were screened into study group by inclusion and exclusion standards. The symptom check list 90 (SCL-90) was used to group and score the mental state of these patients according to nine classification criteria: gender, BMI, age, marital status, monthly salary, disease duration, living environment, education level and working environment. Then, the scores were compared within groups. Inter-group comparison was made between the study group and the Chinese norm, and the positive factors for psychological disorders were extracted. Four symptoms in the study group, i.e. nasal itching, sneezing, clear discharge and nasal congestion, were scored on the visual analogue scale (VAS). SPSS 19.0 software was used to carry out statistical analysis. Partial correlation analysis was performed between the positive factors and the symptom scores by multiple regression statistical method. Results: The total score of SCL-90 in the study group was 2.64±0.25, which was accorded with mild to moderate mental health impairment. There were 124 (15.0%) without mental health damage, 176 (21.3%) with mild damage, 474 (57.3%) with mild to moderate damage, 41 (5.0%) with moderate to severe damage and 12 (1.4%) with severe damage. The in-group comparison showed that the top three categories of different items were the living environment, gender and working environment. The scores of somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, psychosis, other (sleep, diet) and total average score of urban residents were higher than that of country residents (3.29±0.61 vs 2.65±0.50, 2.81±0.77 vs 2.05±0.38, 3.10±0.19 vs 2.49±0.67, 3.40±0.84 vs 2.49±0.70, 3.04±0.64 vs 2.33±0.51, 3.02±0.55 vs 2.40±0.77, 3.40±0.41 vs 2.52±0.77, 2.91±0.11 vs 2.29±0.40, Z value was 4.88, 5.25, 4.57, 5.91, 5.09, 4.63, 5.55, -4.55, respectively, all P<0.05). Women scored higher than man for somatization, interpersonal sensitivity, depression and others (2.66±0.51 vs 2.00±0.45, 3.37±0.47 vs 2.63±0.51, 3.44±0.57 vs 2.85±0.52, 3.47±0.36 vs 2.76±0.45, Z value was -5.10, -5.51, -4.86, -5.28, respectively, all P<0.05). The scores of somatization, interpersonal sensitivity, psychosis and other (sleep, diet) were higher in the indoor group than those in the outdoor group (3.49±0.64 vs 2.78±0.46, 3.33±0.30 vs 2.56±0.68, 3.28±0.60 vs 2.67±0.31, 3.50±0.85 vs 2.85±0.37, Z value was 5.31, 5.79, 4.89, 5.00, respectively, all P<0.05). The outdoor group scored higher on obsessive-compulsive symptoms, anxiety and hostility (3.44±0.40 vs 2.83±0.35, 3.40±0.50 vs 2.57±0.93, 3.34±0.88 vs 2.69±0.56, Z value was 4.96, 6.22, 5.08, respectively, all P<0.05). The inter-group comparison found that depression, anxiety, psychosis and other (sleep, diet) could be partially correlated with VAS scores as 4 positive factors. The results of partial correlation analysis showed that depression was positively correlated with sneezing and nasal runny discharge, anxiety was positively correlated with nasal itching and nasal obstruction, psychosis was positively correlated with nasal itching and sneezing, and other (sleep, diet) was positively correlated with nasal runny discharge and nasal obstruction. Conclusion AR patients have mild to moderate mental health impairments, which are correlated with AR symptoms.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease and a serious threat to human health. COVID-19 can cause multiple organ dysfunction, such as respiratory and circulatory failure, liver and kidney injury, disseminated intravascular coagulation, and thromboembolism, and even death. The World Health Organization reports that the mortality rate of severe-type COVID-19 is over 50%. Currently, the number of severe cases worldwide has increased rapidly, but the experience in the treatment of infected patients is still limited. Given the lack of specific antiviral drugs, multi-organ function support treatment is important for patients with COVID-19. To improve the cure rate and reduce the mortality of patients with severe- and critical-type COVID-19, this paper summarizes the experience of organ function support in patients with severe- and critical-type COVID-19 in Optical Valley Branch of Tongji Hospital, Wuhan, China. This paper systematically summarizes the procedures of functional support therapies for multiple organs and systems, including respiratory, circulatory, renal, hepatic, and hematological systems, among patients with severe- and critical-type COVID-19. This paper provides a clinical reference and a new strategy for the optimal treatment of COVID-19 worldwide.
Antiviral Agents ; therapeutic use ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; therapy ; Humans ; Oxygen Inhalation Therapy ; Pandemics ; Pneumonia, Viral ; therapy ; Respiration