ABSTRACT
Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.
ABSTRACT
Objective@#To understand the filialpiety values, anxiety and caregiving burden of caregivers of patients with chronic heart failure and to analyze the mediating effect of filialpiety values on the relationship between anxiety and caregiving burden.@*Methods@#During April 2017 to April 2018, 191children caregivers of patients with chronic heart failure from 3 secondary and tertiary medical institutions in Suzhou, Nanjing and Kunshan were selected to complete Visual Analogue Scale for Anxiety, Chinese Filial Values Index scale (FVI) and Dutch Objective Burden Inventory (DOBI).@*Results@#The total score of caregivers' anxiety, filialpiety values and caregiving burden were 3(0, 6), 96(84, 107) and 1(0, 9) respectively. Correlation analysis showed that the caregivers' anxiety was positively correlated with the caregiving burden (r=0.328, P<0.01), while filialpiety values were negatively correlated with caregiving burden (r=-0.537, P<0.01). Mediating-effect analysis showed that anxiety had a negative effect on filialpiety values (a=-0.61, P=0.02), and had a positive effect on caregiving burden (c=0.64, P=0.01). The filialpiety values had a negative effect on caregiving burden (b=-0.43, P<0.01). Filialpiety values played a partial mediating role between anxiety and caregiving burden (c' = 0.26, P<0.05).@*Conclusions@#Medical staff should establish targeted interventions to improve caregivers′ filialpiety values, thereby reducing their caregiving burden.
ABSTRACT
Objective To understand the filialpiety values, anxiety and caregiving burden of caregivers of patients with chronic heart failure and to analyze the mediating effect of filialpiety values on the relationship between anxiety and caregiving burden. Methods During April 2017 to April 2018, 191children caregivers of patients with chronic heart failure from 3 secondary and tertiary medical institutions in Suzhou, Nanjing and Kunshan were selected to complete Visual Analogue Scale for Anxiety, Chinese Filial Values Index scale (FVI) and Dutch Objective Burden Inventory (DOBI). Results The total score of caregivers' anxiety, filialpiety values and caregiving burden were 3(0, 6), 96(84, 107) and 1(0, 9) respectively. Correlation analysis showed that the caregivers' anxiety was positively correlated with the caregiving burden (r=0.328, P<0.01), while filialpiety values were negatively correlated with caregiving burden (r=-0.537, P<0.01). Mediating-effect analysis showed that anxiety had a negative effect on filialpiety values (a=-0.61, P=0.02), and had a positive effect on caregiving burden (c=0.64, P=0.01). The filialpiety values had a negative effect on caregiving burden (b=-0.43, P<0.01). Filialpiety values played a partial mediating role between anxiety and caregiving burden (c' = 0.26, P＜0.05). Conclusions Medical staff should establish targeted interventions to improve caregivers′filialpiety values, thereby reducing their caregiving burden.
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Objective To investigate the prevalence and specific manifestations of enduring psychological distress in patients with breast cancer after operation. Methods Totally 263 patients of the newly diagnosed breast cancer treated with the operation from August 2014 to August 2015 were collected by convenience sampling. Distress Thermometer (DT) and Problem List recommended by national Comprehensive Cancer Network was used to assess the persistent psychological distresses in the 6th, 15th, 20th, 25th, 30th months after the disease diagnosis,while a self-designed questionnaire was for the demographic data. Results The results of the DT screening showed that 16％(42/263) patients had persistent psychological problems;the incidences of five stages of significant psychological distress (DT≥4) was 43％(113/263), 34％(89/263), 31％(81/263), 28％ (73/263) and 25％ (65/263), respectively. The main manifestations of persistent psychological distress were:fatigue 59 cases (22.4％) , sleep disorders 51 cases (19.4％), nervous 48 cases (18.2％), anxiety 24 cases (9.1％), fear of appearance 23 cases (8.7％) and the difference in persistent psychological distress scores between different demographic characteristics (age, educational level, marital status, economic situation, operation method, disease stage) were statistically significant (t=-2.295-2.966, P<0.05). Conclusion The incidences of persistent psychological distress in patients with breast cancer is higher and the manifestation is different,which should be paid attention to by medical workers.
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Objective To study the status of filial piety and anxiety among adults, explore the relationship between filial piety and anxiety, and analyze the factors that affect anxiety. Methods A total of 915 adults from Jiangsu and Anhui provinces were selected using the General Information Questionnaire, the Chinese Filial Values Index scale (FVI) and Zung Self-rating Anxiety Scale (SAS), through the online platform and on-site payment, recovery of the questionnaire to investigate. Results The overall level of filial piety was 85.23 ± 9.22 , among which the care dimension was 84.60 ± 9.75 and the respect dimension was 86.12 ± 11.76;111 adults were with anxiety (12.13％), and patients with mild and moderate anxiety respectively were 88 (9.62％) and 23 (2.51％) cases. The overall level of filial piety was negatively correlated with the level of anxiety (r=-0.403, P<0.01), and the level of filial piety is an independent factor affecting the level of anxiety in adults(B=-0.299,P<0.01). Other factors also include the quality of sleep, illness, duration, beliefs, occupational stability. Conclusion The high level of filial piety in adults is moderately correlated with anxiety and is an independent risk factor for anxiety in this population. The adult's education of filial piety should be strengthened and the positive adjustment of filial piety to anxiety should be strengthened in order to better solve the physical and mental health problems caused by the pension burden.