Bortezomib Is Effective in the Treatment of T Lymphoblastic Leukaemia by Inducing DNA Damage, WEE1 Downregulation, and Mitotic Catastrophe.

T lymphoblastic leukemia (T-ALL) is an aggressive haematolymphoid malignancy comprising 15% of acute lymphoblastic leukemia (ALL). Although its prognosis has improved with intensive chemotherapy, the relapse/refractory disease still carries a dismal prognosis. Thus, there is an urgent need to develop novel therapy for T-ALL. Bortezomib, a 26S proteasome inhibitor, is licensed to treat plasma cell myeloma and mantle cell lymphoma. Due to its favorable side effect profile, it is a novel agent of research interest in the treatment of ALL. Despite an increasing number of clinical trials of bortezomib in T-ALL, its detailed mechanistic study in terms of DNA damage, cell cycle, and mitotic catastrophe remains elusive. Moreover, WEE1, a protein kinase overexpressed in ALL and involved in cell-cycle regulation, has been known to be a novel therapeutic target in many cancers. But the role of bortezomib in modulating WEE1 expression in ALL still remains elusive. In this study, we demonstrate the therapeutic efficacy of bortezomib on T-ALL primary samples and cell lines. Our findings reveal that bortezomib treatment induces DNA damage and downregulates WEE1, leading to G2-M cell-cycle progression with damaged DNA. This abnormal mitotic entry induced by bortezomib leads to mitotic catastrophe in T-ALL. In conclusion, our findings dissect the mechanism of action of bortezomib and provide further insights into the use of bortezomib to treat T-ALL. Our findings suggest the possibility of novel combination therapy using proteasome inhibitors together with DNA-damaging agents in the future, which may fill the research gaps and unmet clinical needs in treating ALL.

Rural-urban differences in home-based care willingness among older adults: A cross-sectional study in Shandong, China.

OBJECTIVE: To examine the rural-urban disparities of home-based care willingness among older adults and identify the influencing factors. DESIGN: A cross-sectional study. SETTING: The data used in this cross-sectional study were conducted in Shandong province. STUDY PARTICIPANTS: 7070 older adults (60 years and older) with complete data were included in this analysis from the 2017 Survey of the Shandong Elderly Family Health Service. INTERVENTION: N/A. MAIN OUTCOME MEASURE: The data were analyzed using logistic regression models to examine whether socio-demographic characteristic, physical health, loneliness score and other factors were associated with home-based care willingness in rural and urban older adults. After exploring the factors, we compared the difference. RESULTS: Of 7070 participants, 66.9% were rural older adults and 33.1% were urban. The urban older adults less likely chose home-based care than the rural (OR = 0.667; P < 0.05). Binary logistic regression analysis showed that age (P < 0.05), income (P < 0.05), current employment (P < 0.05) and loneliness (P < 0.05) were significantly associated with the home-based care willingness both in rural and urban residence. Besides, the number of family members (P = 0.010), education years (P = 0.026) and financial support from children (P = 0.017) were associated factors of rural respondents' home-based care willingness. The bad self-reported-health-status-urban-older adults (P = 0.026) were more willing for home-based care. CONCLUSIONS: The research we have done suggests that there is a residence difference toward home-based care willingness among older adults. Targeted policies and an age-friendly environment should be made for different subgroups of older adults.

Gender difference in suicidal ideation and related factors among rural elderly: a cross-sectional study in Shandong, China.

BACKGROUND: Suicide is a global public health problem which has significant negative influence on individuals, families and the society. The aim of this study is to investigate the prevalence of suicidal ideation and related factors among elderly people in rural China, and further examine the gender differences of suicidal ideation. METHODS: Data were collected from the 2017 Survey of the Shandong Elderly Family Health Service, which was conducted by Shandong University. A total of 5514 elderly aged 60 and above from rural Shandong were included in this study. Binary logistic regression model was performed to examine the gender difference towards suicidal ideation, and to identify the influencing factors of suicidal ideation by gender among elderly. RESULTS: 7.7% rural elderly reported suicidal ideation in the past 12 months in Shandong, China. The prevalence of suicidal ideation among females was significantly higher than that among males (P < 0.001). Education level, debts, stress of daily life, loneliness and psychological distress were significantly related to suicidal ideation in both males and females. Besides, negative life events and life satisfaction were found to be significantly associated with suicidal ideation in females but not in males. CONCLUSIONS: There was a significant gender difference towards suicidal ideation among rural elderly in Shandong, China. So, gender difference should be considered when medical practitioners and public health workers seek to prevent and manage suicidal ideation among rural elderly, which will be important to develop strategies for coping with risk factors for suicidal ideation among males and females. In other words, more attention should be paid to females who had encountered negative life event or with lower life satisfaction.

The Willingness for Downward Referral and Its Influencing Factors: A Cross-Sectional Study among Older Adults in Shandong, China.

Objectives: The aim of this study was to understand the willingness for downward referral among older adults who were hospitalized in the year before the survey and to explore its influencing factors. Methods: The sample was randomly selected by the multi-stage sampling method. A structural questionnaire was used to collect data from participants age 60 and above in Shandong, China, during August 2017. Data were analyzed by using descriptive statistics, one-way ANOVA, chi-square test, and multinomial logistic regression. Results: Of 1198 participants who were hospitalized in the year before the survey, 28.7% self-initiated downward referral, and 33.9% were willing to accept downward referral after a doctor's advice. Multinomial logistic regression results showed that self-rated health, treatment effect in primary medical institutions, preference for outpatient service, choice of inpatient service, general understanding of essential medicines, the cost of essential medicines after zero-markup policy, and satisfaction with essential medicines' reimbursement policy significantly correlated with older adults' willingness for downward referral. Conclusions: The proportion of older adults who self-initiated downward referral was less than one-third. Doctors' advice plays an important role in willingness for downward referral. More attention should be paid to improving the treatment effect of primary medical institutions, increasing the benefits of zero-markup policy, and ensuring a high reimbursement for the downward referral to work alongside doctors' advice.

Gender Difference in General Self-Efficacy among Young-Old Elderly Aged 60-74 in Rural Shandong China: A Cross-Sectional Survey.

OBJECTIVE: This study aims to explore the determinants of general self-efficacy (GSE) among young-old elderly, with focus on examining the gender difference of general self-efficacy. METHODS: Data were collected from the 2017 Survey of the Shandong Elderly Family Health Service, which was conducted by Shandong University. T-test was used to examine the gender difference in GSE. Univariate models and adjusted multiple linear regression model were used to explore the determinants of GSE by gender. RESULTS: The females' GSE score was lower than that of male participants (26.1 ± 8.1 vs. 28.7 ± 7.7), and there was a significant gender difference (t = 10.877, p < 0.001). Multiple linear regression model showed that some factors are common significant determinants of GSE such as age, education level, activity of daily living (ADL), self-rated health, mental health, personality, and whether participants have intimate friends and interpersonal relationships. Hypertension and frequent communication with children were specific determinants of GSE among male young-old. Personal income was a specific determinant of female participants. CONCLUSION: Some influencing factors of GSE in both genders are identical, the others are different. More attention should be paid for the poor young-old females, young-old males with hypertension, and disabled young-old people.