Occupational physical activity, all-cause, cardiovascular disease, and cancer mortality in 349,248 adults: Prospective and longitudinal analyses of the MJ Cohort

Background:Evidence on the health benefits of occupational physical activity(OPA)is inconclusive.We examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer mortality and survival times.Methods:This study included prospective and longitudinal data from the MJ Cohort,comprising adults over 18 years recruited in 1998-2016,349,248 adults(177,314 women)with baseline OPA,of whom 105,715(52,503 women)had 2 OPA measures at 6.3±4.2 years(mean±SD)apart.Exposures were baseline OPA,OPA changes,and baseline leisure-time physical activity.Results:Over a mean mortality follow-up of 16.2±5.5 years for men and 16.4±5.4 years for women,11,696 deaths(2033 of CVD and 4631 of cancer causes)in men and 8980 deaths(1475 of CVD and 3689 of cancer causes)in women occurred.Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men(multivariable-adjusted hazard ratio(HR)=0.93,95%confidence interval(95%CI):0.89-0.98 compared to light OPA)and women(HR=0.86,95%CI:0.79-0.93).Over a mean mortality follow-up of 12.5±4.6 years for men and 12.6±4.6 years for women,OPA decreases in men were detrimentally associated(HR=1.16,95%CI:1.01-1.33)with all-cause mortality,while OPA increases in women were beneficially(HR=0.83,95%CI:0.70-0.97)associated with the same outcome.Baseline or changes in OPA showed no associations with CVD or cancer mortality.Conclusion:Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women.Our longitudinal OPA analyses partly confirmed the prospective findings,with some discordance between sex groups.

Can physical activity eliminate the mortality risk associated with poor sleep?A 15-year follow-up of 341,248 MJ Cohort participants

Background:This study examined the joint associations of sleep patterns and physical activity(PA) with all-cause,cardiovascular disease(CVD),and cancer mortality.Methods:A total of 341,248 adults(mean age=39.7 years;men:48.3%) were included in the study,with a 15-year follow-up.Participants reported sleep duration and disturbances(difficulty falling asleep,easily awakened,or use of sleeping medication).PA was classified into 4 levels:<7.5,7.5-14.9,15.0-29.9,and>30.0 metabolic equivalent hours per week(MET-h/week).To understand the joint associations of sleep patterns and PA with mortality,Cox proportional hazard models were conducted,with exposure variables combining sleep duration/disturbances and PA.Results:Compared with the reference group(sleeping 6-8 h/day),individuals who slept>8 h/day had higher risk for all-cause mortality(hazard ratio(HR)=1.307,95% confidence interval(95%CI):1.248-1.369),CVD mortality(HR=1.298,95%CI:1.165-1.445),and cancer mortality(HR=1.128,95%CI:1.042-1.220).Short sleep duration was not associated with mortality risk.Increased risk of all-cause and CVD mortality was found in participants who had difficulty falling asleep(HR=1.120,95%CI:1.068-1.175;HR=1.163,95%CI:1.038-1.304,respectively),and used sleeping medication(HR=1.261,95%CI:1.159-1.372;HR=1.335,95%CI:1.102-1.618,respectively) compared with those who slept well.Long sleep duration and sleep disturbances were not associated with risk of all-cause and CVD mortality among individuals achieving a PA level of>15 MET-h/week,and in particular among those achieving> 30 MET-h/week.Conclusion:Long sleep duration,difficulty falling asleep,and use of sleeping medication were related to a higher risk of death.Being physically active at a moderate intensity for 25-65 min/day eliminated these detrimental associations.

Activation of phagocytosis by immune checkpoint blockade

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-a （SIRPa）, on tumor-associated macrophages （TAMs） and its cognate ligand cluster of differentiation 47 （CD47） on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 （PD-1） in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.