Immune checkpoint blockade therapy has been successful in treating some types of cancers but has not shown clinical benefits for treating leukemia 1 . This result suggests that leukemia exploits unique escape mechanisms. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukemia cells. It remains unknown whether these receptors can initiate immune-related primary signaling in tumor cells. Here we show that LILRB4, an ITIM-containing receptor and a monocytic leukemia marker, supports tumor cell infiltration into tissues and suppresses T cell activity via ApoE/LILRB4/SHP-2/uPAR/Arginase-1 signaling axis in acute myeloid leukemia (AML) cells. Blocking LILRB4 signaling using knockout and antagonistic antibody approaches impeded AML development. Thus, LILRB4 orchestrates tumor invasion pathways in monocytic leukemia cells by creating an immune-suppressive microenvironment. LILRB4 represents a compelling target for treatment of monocytic AML.

Help-seeking is important to access appropriate care and improve mental health. However, individuals often delay or avoid seeking help for mental health problems. Interventions to improve help-seeking have been developed, but their effectiveness is unclear. A systematic review and meta-analysis were therefore conducted to examine the effectiveness of mental health related help-seeking interventions. Nine databases in English, German and Chinese were searched for randomised and non-randomised controlled trials. Effect sizes were calculated for attitudes, intentions and behaviours to seek formal, informal and self-help. Ninety-eight studies with 69 208 participants were included. Interventions yielded significant short-term benefits in terms of formal help-seeking, self-help, as well as mental health literacy and personal stigma. There were also positive long-term effects on formal help-seeking behaviours. The most common intervention types were strategies to increase mental health literacy, destigmatisation (both had positive short-term effects on formal help-seeking behaviours) as well as motivational enhancement (with positive long-term effects on formal help-seeking behaviours). Interventions improved formal help-seeking behaviours if delivered to people with or at risk of mental health problems, but not among children, adolescents or the general public. There was no evidence that interventions increased the use of informal help. Few studies were conducted in low- and middle-income countries (LMICs). This study provides evidence for the effectiveness of help-seeking interventions in terms of improving attitudes, intentions and behaviours to seek formal help for mental health problems among adults. Future research should develop effective interventions to improve informal help-seeking, for specific target groups and in LMICs settings.

BackgroundHeavy fine particulate matter (PM2.5) air pollution occurs frequently in China. However, epidemiological research on the association between short-term exposure to PM2.5 pollution and respiratory disease morbidity is still limited. This study aimed to explore the association between PM2.5 pollution and hospital emergency room visits (ERV) for total and cause-specific respiratory diseases in urban areas in Beijing.MethodsDaily counts of respiratory ERV from Jan 1 to Dec 31, 2013, were obtained from ten general hospitals located in urban areas in Beijing. Concurrently, data on PM2.5 were collected from the Beijing Environmental Protection Bureau, including 17 ambient air quality monitoring stations. A generalized-additive model was used to explore the respiratory effects of PM2.5, after controlling for confounding variables. Subgroup analyses were also conducted by age and gender.ResultsA total of 92,464 respiratory emergency visits were recorded during the study period. The mean daily PM2.5 concentration was 102.1±73.6 μg/m3. Every 10 μg/m3 increase in PM2.5 concentration at lag0 was associated with an increase in ERV, as follows: 0.23% for total respiratory disease (95% confidence interval [CI]: 0.11%-0.34%), 0.19% for upper respiratory tract infection (URTI) (95%CI: 0.04%-0.35%), 0.34% for lower respiratory tract infection (LRTI) (95%CI: 0.14%-0.53%) and 1.46% for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (95%CI: 0.13%-2.79%). The strongest association was identified between AECOPD and PM2.5 concentration at lag0-3 (3.15%, 95%CI: 1.39%-4.91%). The estimated effects were robust after adjusting for SO2, O3, CO and NO2. Females and people 60 years of age and older demonstrated a higher risk of respiratory disease after PM2.5 exposure.ConclusionPM2.5 was significantly associated with respiratory ERV, particularly for URTI, LRTI and AECOPD in Beijing. The susceptibility to PM2.5 pollution varied by gender and age.

SARS-CoV-2 is a spherical, enveloped, single-stranded positive RNA virus with a diameter of 80 nm-160 nm and a genome size of 29.9 kb