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@#N6-methyladenine (m6A) modification, the most abundant and dynamic chemical modification on messenger RNA, plays an essential role in physiological and pathological progress.Recent studies have found that tumor progression can be affected by altering the m6A modification level of target genes. Therefore, small molecule targeted m6A demethylase can be used as a new anti-tumor strategy.This review focuses on the regulatory mechanism of m6A demethylases, including fat mass and obesity-associated protein (FTO) and AlkB homlog 5 (ALKBH5), as well as their biological functions in tumors, and summarizes the research progress of their small molecule inhibitors.
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OBJECTIVE：To s ystematically review the economics of osimertinib for advanced non-small cell lung cancer （NSCLC），and to provide the reference for clinical application and healthcare decision makers. METHODS ：Retrieved from PubMed，Embase，the Cochrane L ibrary，Health Technology Assessment ，CNKI，Wanfang database ，VIP，CBM，etc.， pharmacoeconomic studies on osimertinib in the treatment of advanced NSCLC were collected from the inception to Apr. 2020. After screening and extracting relevant data ，the quality of the included studies was evaluated by using the Quality of Health Economics Studies （QHES），and the economic research results of the included literatures were systematically evaluated by using descriptive analysis method. RESULTS & CONCLUSIONS ：A total of 10 studies from 7 different countries were included ；QHES scores of the included literatures were 73-93，with an average of 86.8，and the quality of the researches was generally high. All the 10 studies were cost-effectiveness analysis ，including 6 first-line treatment ，4 second-line treatment. Six studies reported the cost discount rate ；only one study used the cost of osimertinib after price reduction for evaluation and analysis. Compared with other epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI），six studies from different countries showed that osimertinib as the first-line treatment drug had no cost-effectiveness advantage ；cost-effectiveness of second-line treatment of osimertinib was controversial ，compared to chemotherapy. For advanced NSCLC patients ，the second-line treatment of osimertinib after the national centralized negotiation of price reduction has a more cost-effectiveness advantage in China ’s medical service system，while the first-line treatment of osimertinib before price reduction does not have this advantage compared with other EGFR-TKI drugs.
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OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.
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Objective@#To exmain reliability and validity of the Chinese version of Family Hardiness Index(FHI) among patients with cancer.@*Methods@#A convinent sample of 344 patients with cancer was investigated with a self-designed questionnaire about personal information, the Herth Hope Index (HHI) and the Chinese version of FHI. Item analysis was conducted on each item of the Chinese version of FHI; The construct validity of the scale were evaluated by explorotory factor analysis, the reliability of the scale was also evaluated by calculating the Cronbach α coefficient, the split-half reliability and the retest reliability.@*Results@#The Chinese version of FHI consisted of 20 items. Five factors were extracted by factor analysis which explained 57.900% of the total variance. The score of the Chinese version of FHI was significantly correlated to the total score of HHI (r=0.716, p<0.01) .The Cronbach α coefficient of the Chinese version of FHI was 0.806, and the test-retest reliability coefficient was 0.790 and The split-half reliability was 0.793.@*Conclusion@#The Chinese version of FHI demonstrates good reliability and validity during initial testing among patients with cancer.
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OBJECTIVE To screen small molecule compounds from traditional Chinese medicine that can enhance recombinant adeno-associated virus (rAAV) transduction. METHODS Recombinant adeno-associated virus (rAAV) has been established as a powerful tool for in vivo gene transfer and achieved much promise in gene therapy applications. However, widespread clinical use has been limited by transduction efficiency.In the current study,we screened a panel of small molecule compound from traditional Chinese medicine focused on AAV intracellular trafficking process and found salvianolic acid B can significantly enhance rAAV2 transduction. RESULTS Salvianolic acid B caused a dose-depen-dent increase in rAAV2 transduction regardless of vector dose,genome architecture,and over a broad range of cell line from various cell type and species(HEK293,HeLa,HepG2,Huh-7,CHO-K1,LO-2). Salvianolic acid B treatment redirected rAAV2 particles toward large vesicles positive for late endosomal (Rab7)and lysosomal(LAMP1)markers.Furthermore,salvianolic acid B acted to increase accumulation of viral particles at the perinuclear region. CONCLUSION In summary, our results suggest that salvi-anolic acid B redirects rAAV2 toward more productive trafficking pathways and stabilizes perinuclear accumulations of vectors,facilitating productive nuclear trafficking.
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Objective To explore the effects of guideline-based symptom cluster management program on the severity of fatigue, pain, sleep disturbance and the quality of life in lung cancer patients. Methods A total of 88 lung cancer patients admitted from July 2017 to November 2017 were divided into the intervention group and the control group with 44 cases in each group by the wards. The control group received routine nursing. The intervention group received health education and related skills guidance about symptom management of fatigue,pain and sleep disturbance on the basis of routine. The severity of fatigue, pain, sleep disturbance and quality of life were compared between the 2 groups after 3 weeks intervention. Results After 3 weeks intervention, the scores of fatigue,pain and sleep disturbance in the intervention group were 3.65 ± 0.97, 2.44 ± 0.79, 9.30 ± 2.41 respectively,the scores in the control group were 3.89 ± 1.05, 2.77 ± 0.88, 10.09 ± 1.97 respectively. There was no statistically significant differences in fatigue score (F=1.60,P>0.05),but there were statistically significant differences in pain and sleep disturbance scores between two groups (F=7.83, 5.13, all P<0.05). The scores of quality of life, physical, psychological, social, environmental domains in the intervention group were 52.42 ± 4.71,14.02 ± 2.05, 12.39±2.36, 14.39±2.45, 11.61±1.84 respectively,the control group were 50.77±4.11, 13.31±2.21, 11.89 ± 2.04, 13.65 ± 2.69, 11.92 ± 1.86 respectively. There was no statistically significant differences in scores of psychological and environmental domains (F=0.52, all P>0.05), but there were statistically significant differences in total score, scores of physical and social domains between two groups(F=5.03-6.86, all P<0.05). Conclusion The guideline-based management program could effectively control the deterioration of the severity of fatigue,pain,sleep disturbance and improve patient's quality of life.
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Objective To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults.Methods A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire.TL was measured by fluorescence quantitative PCR.The correlation and regression analysis between sleep and telomere length was performed.Results TL had a mean T/S ratio of 0.995 ± 0.23.There was a negative correlation between TL and age (r=-0.241,P=0.003).With increasing age,sleep quality became worse (r=-0.230,P＜0.01),the time to fall asleep became longer (r=0.227,P＜0.01),sleep duration was shorter (r=-0.486,P＜0.01),sleep efficiency became worse (r=-0.226,P＜0.01).After controlling for the effects of gender,age,marital status,income level,residence,smoking,drinking,physical exercise and disease status,multiple linear regression analysis indicated that sleep quality (β3=0.057,P＜0.01),time to fall asleep (β =-0.046,P＜0.01),sleep duration (β3=0.086,P＜0.01) were independent influencing factors of telomere length,suggesting that the people who had better sleep quality,the shorter time to fall asleep,the longer sleep time would have longer telomere length.Conclusions Sleep is a relevant factor affecting TL in middle-aged and elderly population.Good sleep may delay aging by slowing TL.We encourage to conduct health education about the importance of sleep quality in community.
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Objective To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults.Methods A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire.TL was measured by fluorescence quantitative PCR.The correlation and regression analysis between sleep and telomere length was performed.Results TL had a mean T/S ratio of 0.995 ± 0.23.There was a negative correlation between TL and age (r=-0.241,P=0.003).With increasing age,sleep quality became worse (r=-0.230,P＜0.01),the time to fall asleep became longer (r=0.227,P＜0.01),sleep duration was shorter (r=-0.486,P＜0.01),sleep efficiency became worse (r=-0.226,P＜0.01).After controlling for the effects of gender,age,marital status,income level,residence,smoking,drinking,physical exercise and disease status,multiple linear regression analysis indicated that sleep quality (β3=0.057,P＜0.01),time to fall asleep (β =-0.046,P＜0.01),sleep duration (β3=0.086,P＜0.01) were independent influencing factors of telomere length,suggesting that the people who had better sleep quality,the shorter time to fall asleep,the longer sleep time would have longer telomere length.Conclusions Sleep is a relevant factor affecting TL in middle-aged and elderly population.Good sleep may delay aging by slowing TL.We encourage to conduct health education about the importance of sleep quality in community.
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BACKGROUND:There are less reports on how to successfuly build the internal spatial configuration of tissue-engineered tooth scaffolds. OBJECTIVE:To find a way to establish a series of three-dimensional digital modes for tissue-engineered tooth scaffold, such as CAD spatial configuration and Standard Template Library (STL) files. METHODS:In order to get three-dimensional printing format of STL files, MICRO CT data of DICOM format were input into MIMICS and GEOMAGIC softwares, creating the outline of STL files. Then CATIA V5R17 software was used to create the three-dimensional digital mode of tissue-engineered tooth. Then, the overal model of the internal scaffold was obtained by arraying at the proper coordinates. Various overal scaffold configurations could be built rapidly by varying monomer configuration. The STL files of CAD model of three-dimensional printing tissue-engineered tooth were obtained by assembling the tooth outline mode and the internal scaffold. RESULTS AND CONCLUSION: The CAD model was constructed successfuly, and this model could be directly used for three-dimensional printing rapid prototyping system to produce tissue-engineered tooth scaffolds. These findings indicate that the three-dimensional digital mode based on reverse engineering and positive engineering can be established, which can be used to quickly build a variety of internal spatial configurations of scaffold materials required for tissue-engineered teeth.
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AIM:To evaluate the efficiency of vitrectomy combined with inferior scleral buckling for a special kind of retinal detachment. METHODS: Nineteen eyes of special retinal detachment had following features: 1 ) the course was more than 6mo;2) there were at least one hole located in the 5 : 00 - 7 : 00 of the marginal retina; 3 ) the detachment range of retina more than 270 degrees and retinal proliferation in retinal detachment. The 19 eyes who received vitrectomy combined with inferior scleral buckling, retinal anatomic reattachment and visual function recovery was observed. RESULTS: Among these 19 eyes, all eyes retinal anatomic reattachment and best corrected visual acuity ( BCVA ) was improved in various degrees. The BCVA was 0. 01-0. 1 in 5 eyes, 0. 12-0. 3 in 9 eyes, and ≥0. 4 in 5 eyes. CONCLUSION: It is an effective method to vitrectomy combined with inferior scleral buckling for the special kind of retinal detachment which has following features:1) the course was more than 6mo;2) there were at least one hole located in the 5:00-7:00 of the marginal retina;3 ) the detachment range of retina more than 270 degrees and retinal proliferation of cable in retinal detachment.
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METHODS:Lentiviral vectors carrying bFGF and BMP-2 were constructed to transfect sheep bone marrow mesenchymal stem cells. cells were divided into four groups:bFGF group, BMP-2 group, co-transfection group BACKGROUND:Basic fibroblast growth factor (bFGF) can promote the proliferation of bone marrow stromal cells, and bone morphogenetic protein-2 (BMP-2) has an important significance in the induction of new bone formation. OBJECTIVE:To analyze the effects of bFGF, BMP-2 and their co-transfection on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells and to compare the relative expressions of col agen I, osteocalcin and osteopontin before and after celltransfection, thereby providing theoretical implications for seed cells in the construction of tissue-engineered bone. and control group. The RNA was extracted using real-time quantitative PCR to detect mRNA levels of col agen I, osteocalcin, and osteopontin. RESULTS AND CONCLUSION:Significant difference in non-specific osteogenic gene expressions was found among the four groups (P0.05). In vitro experiments showed that the relative expression of col agen I, osteocalcin and osteopontin were higher in the co-transfection group, indicating the cells from the co-transfection group have strongest osteogenic capacity that are suitable for seed cells for bone tissue engineering.