Background Emerging evidence supports the pivotal roles of adipocytes in breast cancer progression. Tumour induced beige/brown adipose tissue differentiation contributes to the hypermetabolic state of the breast cancer. However, the mediators and mechanisms remain unclear. Methods Survival probabilities were estimated using the Kaplan–Meier method based on immunohistochemistry results. Biochemical studies were performed to characterize the novel interrelation between breast cancer cells and adipocytes. Results We show that tumour-surrounding adipocytes exhibit an altered phenotype in terms of upregulated beige/brown characteristics and increased catabolism associated with an activated state characterized by the release of metabolites, including free fatty acids, pyruvate, lactate and ketone bodies. Likewise, tumour cells cocultivated with mature adipocytes exhibit metabolic adaptation and an aggressive phenotype in vitro and in vivo. Mechanistically, we show that tumour cells induce beige/brown differentiation and remodel metabolism in resident adipocytes by exosomes from the co-culture system that carry high levels of miRNA-144 and miRNA-126. miRNA-144 promotes beige/brown adipocyte characteristics by downregulating the MAP3K8/ERK1/2/PPARγ axis, and exosomal miRNA-126 remodels metabolism by disrupting IRS/Glut-4 signalling, activating the AMPK/autophagy pathway and stabilizing HIF1α expression in imminent adipocytes. In vivo inhibition of miRNA-144 or miRNA-126 decreases adipocyte–induced tumour growth. Conclusions These results demonstrate that by inducing beige/brown differentiation and enhancing catabolism in recipient adipocytes, exosomal miRNA-144 and miRNA-126 from the tumour-adipocyte interaction reprogram systemic energy metabolism to facilitate tumour progression. Electronic supplementary material The online version of this article (10.1186/s13046-019-1210-3) contains supplementary material, which is available to authorized users.

PurposeThis study was to present the 2016 prevalence estimates of Chinese school-aged children meeting physical fitness standards and to examine differences by sex and residence locales in children who did not meet fitness standards.MethodsWe conducted cross-sectional analyses of 171,991 children and adolescents (boy: 50.0%, Grades 1–12) who participated in the 2016 Physical Activity and Fitness in China—The Youth Study. The main outcomes were fitness measures, assessed by the 2014 revised Chinese National Student Physical Fitness Standard (CNSPFS), covering areas of aerobic capacity, upper body strength, flexibility, body mass index, abdominal strength, and trunk strength. Children's overall physical fitness performance was categorized, per CNSPFS standards, as excellent, good, pass, or no pass. Data on the prevalence of physical fitness categories and not meeting fitness standards (i.e., among children who received a “no pass” mark) were analyzed, through logistic regression, by sex (boy, girl) and residence locales (urban, rural) across 3 school grades (primary, junior middle, and junior high).ResultsIn 2016, 5.95% of Chinese children and adolescents achieved an “excellent” mark, 25.80% received a “good” rating, 59.90% received a “pass”, and 8.35% received a “no pass”. Overall, boys were more likely to not pass the fitness standards compared with girls (adjusted odds ratio (aOR) = 1.710; 95% confidence interval (CI): 1.708–1.712) and children living in urban areas were more likely to not pass the standards than those living in rural areas (aOR = 1.298; 95%CI: 1.296–1.299). Consistent patterns of not meeting fitness standards were also found by sex and residence locales across all 3 school grades.ConclusionIn the Chinese school-aged population, about 3 in 10 children achieved an “excellent” or “good” fitness standard in 2016, and about 8% of this population did not meet CNSPFS standards. Children living in urban areas were more likely to not meet minimum fitness performance levels, and boys in school were more likely to not meet minimum fitness performance levels than girls.

Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086–1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan–Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts.

BackgroundChina adopted family doctor (FD) to help achieve “Healthy China 2030” through providing continuous, comprehensive, and life-cycle contract services. However, there is a disparity between actual and targeted FD use, as residents continue to visit specialists in large hospitals. The government implemented initiatives to improve residents’ willingness to sign up with and visit their FDs. Factors that influence contract behavior are therefore significant for frontier policy research.MethodsTwo survey waves were conducted in Shanghai (2013 and 2016). The first wave included 2754 people and the second 1995 people. Exploratory factor analysis was used to synthesize “satisfaction” as a predictor of contract behavior. Pearson’s chi-square, pooled and logistic regression models were used to estimate associations between influencing factors and contract behavior, and clarify variations in factors across the two waves.ResultsFour factors were extracted from 15 satisfaction items: “Treatment Environment,” “Medical Technology,” “Service Specification” and “Service Attitude”. Consistent with descriptive analysis, longitudinal analysis showed sociodemographic characteristics (age, education, marital status, and hukou) were significant predictors of contract behavior. The odds ratio of non-communicable diseases (NCD) patients for contract behavior was 2.218 times that of residents without NCD. Contract behavior was positively correlated with awareness of FD services (OR = 21.674, 95%CI = 15.043–31.229), satisfaction with Service Attitude (OR = 1.210, 95%CI = 1.009–1.451), and visit compliance (OR = 1.959, 95%CI = 1.564–2.452). Over time, the odds ratios of the married, Shanghai hukou, NCD, and awareness of FD services declined from 0.456, 1.795, 2.492, 28.690 to 0.443, 1.678, 1.910 and 14.031 respectively, while those of age, and visit compliance increased from 1.027, 1.521 to 1.041 and 2.305 respectively. In 2016, an education-contract gradient had formed (the higher the education level, the higher probability of signing with a FD), whereas high school education had the highest odds ratio (OR = 1.163,95%CI = 0.740–1.827) in 2013. Service Attitude was the only significant satisfaction-related predictor (OR = 1.358, 95%CI = 1.001–1.842) in 2016, compared with “Treatment Environment” (OR = 1.224, 95%CI = 1.001–1.496) and “Service Specification” in 2013(OR = 1.270, 95%CI = 1.040–1.552).ConclusionsExcept for the socio-demographic variables, NCD, awareness of FD services, satisfaction and visit compliance were significant predictors of contract behavior with FDs. The effect of visit compliance had increased over time while NCD and awareness of FD services were losing impact over time. Significant satisfaction factors had also changed from “Treatment Environment” and “Service Specification” to “Service Attitude”.