OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

Objective:To compare and analyze the differences of exercise cardiopulmonary function and the correlation of different cardiopulmonary function indexes among different aircraft types in pilots.Methods:Retrospective study was used. The exercise cardiopulmonary function of 68 Air Force pilots who were qualified for flight in aeromedical identification were tested with the Italian Cosmed exercise cardiopulmonary function tester at a power increasing rate of 25 W/min. The subjects were divided into fighter group and other aircraft group according to aircraft types. The differences of exercise cardiopulmonary function between 2 groups were compared. The correlation between maximal oxygen uptake and age, body mass index, and the correlation between heart rate recovery and exercise endurance were analyzed.Results:There were significant differences in maximal heart rate, respiratory quotient and heart rate recovery value at 1 min after exercise between fighter group (32 cases) and other aircraft group (36 cases) ( t=2.28, 2.50, 2.37, P=0.026, 0.049, 0.021). There was no significant difference in other indexes. The maximal oxygen uptake was negatively correlated with age and body mass index ( r=-0.329, -0.339, both P<0.001). The values of heart rate recovery at 2 min and 3 min after exercise were positively correlated with maximal oxygen uptake and maximal exercise power ( r=0.284, 0.290, 0.306, 0.268, P=0.001, 0.026, 0.002, 0.002). Conclusions:The indexes of exercise cardiopulmonary function have significant differences among pilots in different aircraft types, and there are significant changes with age and weight gain. The heart rate after exercise can monitor the changes of cardiopulmonary function under different training conditions.

Objective:To compare and analyze the differences of exercise cardiopulmonary function and the correlation of different cardiopulmonary function indexes among different aircraft types in pilots.Methods:Retrospective study was used. The exercise cardiopulmonary function of 68 Air Force pilots who were qualified for flight in aeromedical identification were tested with the Italian Cosmed exercise cardiopulmonary function tester at a power increasing rate of 25 W/min. The subjects were divided into fighter group and other aircraft group according to aircraft types. The differences of exercise cardiopulmonary function between 2 groups were compared. The correlation between maximal oxygen uptake and age, body mass index, and the correlation between heart rate recovery and exercise endurance were analyzed.Results:There were significant differences in maximal heart rate, respiratory quotient and heart rate recovery value at 1 min after exercise between fighter group (32 cases) and other aircraft group (36 cases) ( t=2.28, 2.50, 2.37, P=0.026, 0.049, 0.021). There was no significant difference in other indexes. The maximal oxygen uptake was negatively correlated with age and body mass index ( r=-0.329, -0.339, both P<0.001). The values of heart rate recovery at 2 min and 3 min after exercise were positively correlated with maximal oxygen uptake and maximal exercise power ( r=0.284, 0.290, 0.306, 0.268, P=0.001, 0.026, 0.002, 0.002). Conclusions:The indexes of exercise cardiopulmonary function have significant differences among pilots in different aircraft types, and there are significant changes with age and weight gain. The heart rate after exercise can monitor the changes of cardiopulmonary function under different training conditions.

Objective:To analyze the health development plans of the provinces in China during the " 14th Five-Year Plan" , and explore the key tasks, similarities and differences of health informatization construction in each province.Methods:Using the website of local people′s government and the official website of the provincial Health Commission, 27 copies of health development plans of various provinces during the " 14th Five-Year Plan" period were retrieved and collected from February 16 to June 5, 2022. The relevant statements of health information in the plan were extracted, content analysis was used to reveal the structural characteristics of the policy in the form of word frequency statistics, and discourse analysis was used to study the policy content.Results:The health information policies of 27 provinces during the " 14th Five-Year Plan" period could be summarized as 10 major themes, such as accelerating the construction of hierarchical diagnosis and treatment system, promoting the high-quality development of public hospitals, and deepening the reform of medical security system. The health information policy in the eastern, central and western regions was relatively clear, and there were certain differences in the construction points according to their own characteristics.Conclusions:During the " 14th Five-Year Plan" period, the policies of each province around the field of health information are well defined, and the core structure and content are similar. The distribution of key points in the eastern region is relatively balanced; the construction of health information in the central region is more prioritized and prominent; the construction of health information in the western region is focused on complementing the weak links and weaknesses.

Objective:To analyze the filing mechanism for cross provincial immediate reimbursement of medical insurance in China, so as to provide reference for optimizing the filing mechanism and improving the filing accessibility of insured personnel.Methods:Taking the filing policy of cross provincial immediate reimbursement of medical insurance in 2019 as the research object, on the basis of a comprehensive understanding of the national filing policy background, 90 coordinating regions in Zhejiang Province, Hubei Province and Ningxia Hui Autonomous Region were taken as survey samples to evaluate the relevant policies and extract key parameters, including filing identification methods, filing-related settlement benefits and filing ways. The parameters were compared and analyzed by using descriptive statistical methods.Results:The results of the survey showed that in terms of identity recognition methods, the provision of various supporting materials(residence permit, work certificate, etc.)was still the main way to carry out identity recognition for medical insured persons in different places.Filing-related reimbursement benefits were mainly adjusted by limiting the area of medical insurance treatment and adjusting the benefits parameters(reimbursement ratio). In terms of filing channels, 51(56.7%)sample co-ordination areas had realized at least one remote filing mode.Conclusions:The inclusiveness of filing identity verification mechanism for the floating population needs to be further improved, the filing-related treatment policies need to be further improved, and the convenience and standardization of filing channels need to be strengthened.

After recent years′ development, China′s Internet medical service and medical insurance policy system has begun to take shape, but it still needs to be further improved. By combing the connotation and mode of Internet medical services, the evolution of medical insurance payment system and the content of medical insurance payment policy in the United States, the authors put forward that China could further improve the medical insurance payment policy system of Internet medical care, strengthen the multi-point practice management of licensed doctors on the Internet, give full play to the role of commercial insurance in promoting Internet medical care, and rely on information technology means to improve the medical insurance supervision of Internet medical services, then promote the development and management of Internet medical insurance services in China.

Objective:To introduce the formulation and implementation of exercise prescription for military flying personnel.Literature resource and selection:The related literature on exercise prescription of military flying personnel published at home and abroad.Literature quotation:Fifty-eight references were cited, including 46 articles, 6 reviews, 5 dissertations and 1 conference paper.Literature synthesis:Exercise prescription plays an important role in improving the physical function, physical quality, psychological stress and flight ability of flying personnel. The formulation of exercise prescription for flying personnel needs to focus on such aspects as anti-acceleration endurance, muscle strength, exercise ability and cardiopulmonary exercise function. This paper analyzes the elements of exercise prescription for flying personnel, including the selection of exercise type, the control of exercise intensity, the arrangement of exercise time and the setting of exercise frequency.Conclusions:Under the mode of flying personnel′s robust promotion and support, the formulation of individualized moderate intensity exercise prescription according to different types of aircraft, models of aircraft, types of personnel, ages and physical and mental conditions can help flying personnel to improve the physical and mental health and military operation ability.

Objective:To introduce the formulation and implementation of exercise prescription for military flying personnel.Literature resource and selection:The related literature on exercise prescription of military flying personnel published at home and abroad.Literature quotation:Fifty-eight references were cited, including 46 articles, 6 reviews, 5 dissertations and 1 conference paper.Literature synthesis:Exercise prescription plays an important role in improving the physical function, physical quality, psychological stress and flight ability of flying personnel. The formulation of exercise prescription for flying personnel needs to focus on such aspects as anti-acceleration endurance, muscle strength, exercise ability and cardiopulmonary exercise function. This paper analyzes the elements of exercise prescription for flying personnel, including the selection of exercise type, the control of exercise intensity, the arrangement of exercise time and the setting of exercise frequency.Conclusions:Under the mode of flying personnel′s robust promotion and support, the formulation of individualized moderate intensity exercise prescription according to different types of aircraft, models of aircraft, types of personnel, ages and physical and mental conditions can help flying personnel to improve the physical and mental health and military operation ability.

Objective To introduce a practical high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)method for the detection of seven growth hormone-releasing peptides (GHRPs)including GHRP-1,GHRP-2,GHRP-4,GHRP-5,GHRP-6,Hexarelin and Alexamorelin and two growth hormone secretagogues(GHS)including anamorelin and ipamorelin,and study the stability of these nine substances in the human urine.Method The urine samples were purified and extracted by a solid phase extraction procedure using Oasis(R) WCX column.The urine was first centrifuged and taken out 1 mL into a small column,cleaned by 5％ NH4OH and 20％ CH3CN respectively,eluated using the mixture of water and acetomitrile(1/3)with 2％ formic acid,blow-dried in the nitrogen at 35℃ and finally redissolved to be injected into the LC-MS/MS.Result The limits of detection were between 0.01～0.5 ng/mL accordingly.The spiked recoveries at the low concentration(1 ng/mL),medium concentration(2 ng/mL)and high concentration(10 ng/mL)ranged between 40％ and 76％.The intra-and interday precisions of the target substances at these three concentrations were all less than 15％.The indoor temperature,refrigeration condition and multigelation were observed to have significant impact on the anamorelin,GHRP-2,GHRP-4 and GHRP-5.Conclusion The method established in this study is simple,and its specificity and sensitivity meets the international standard and technical documents for laboratories set up by the Wworld Anti-Doping Agency.It has been applied in our routine work.Multigelation should be avoided in the transport,detection and long-term laboratory storage of urine samples.

Quality management covers every corner of hospital services,which upholds full-process quality management,continuous quality improvement and smooth management with patients at the center.By means of building a 3-tier quality management framework at the hospital,development of quality management criteria,appraisal indicators and documentation and use of quality management tools,quality management defects were identified from a third-party perspective.This effort has significantly improved quality of care at the hospital,and elevated the management execution and general service quality of the hospital.