Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by the formation of hamartomas in a wide range of human tissues. Mutation in either the TSC1 or TSC2 tumour suppressor gene is responsible for both the familial and sporadic forms of this disease. TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation). These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR). Furthermore, TSC2 is directly phosphorylated by Akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. TSC2 is inactivated by Akt-dependent phosphorylation, which destabilizes TSC2 and disrupts its interaction with TSC1. Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth.

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We conducted a meta-analysis to examinine the relationship between exposure to PM2.5 and lung cancer incidence and mortality. In total, 17 studies met our inclusion criteria and provided information necessary to estimate the change in lung cancer risk per 10 μg/m3 increase in exposure to PM2.5. The random-effects model was used to estimate the relative risk (RR) for specific PM2.5 values. The meta-estimate for lung cancer risk associated with PM2.5 was 1.11 for mortality (95% CI: 1.05, 1.18) and 1.08 (95% CI: 1.03, 1.12) for incidence. Analyses by continent showed that the meta-estimate for lung cancer mortality associated with PM2.5 was greatest in North America [1.15 (95% CI: 1.07, 1.24)], followed by Asia [1.12 (95% CI: 0.94, 1.35)], and then Europe [1.05 (95% CI: 1.01, 1.10)]. Lung cancer incidence associated with PM2.5 was greatest in Asia [1.09 (95% CI: 1.03, 1.15)], followed by North America [1.06 (95% CI: 1.01, 1.11)], and then Europe [1.03 (95% CI: 0.61, 1.75)]. In subgroup analyses of country, the mortality meta-estimate for developed countries was 1.14 (95% CI: 1.06, 1.23), and for developing countries was 1.03 (95% CI: 1.00, 1.07). The incidence meta-estimate for developed countries was 1.07 (95% CI: 0.96, 1.20), and was similar to that of developing countries, 1.07 (95% CI: 1.06, 1.09). In subgroup analyses of males and females, the meta-estimate for lung cancer mortality associated with PM2.5 was greater for males [1.26 (95% CI: 1.15, 1.40)] than for females [1.17 (95% CI: 0.98, 1.39)]. The meta-estimate for lung cancer incidence associated with PM2.5 was greater for males [1.23 (95% CI: 0.83, 1.81)] than for females [1.15 (95% CI: 1.12, 1.18)]. In subgroup analyses of smoking status, the meta-estimate for lung cancer mortality associated with PM2.5 for former smokers was 1.46 (95% CI: 0.84, 2.55), for current smokers was 1.33 (95% CI: 1.20, 1.49), and for never smokers was 1.16 (95% CI: 1.02, 1.33), respectively. The meta-estimate for lung cancer incidence associated with PM2.5 for former smokers was 1.19 (95% CI: 0.95, 1.50), for never smokers was 1.10 (95% CI: 0.76, 1.59), and for current smokers was 1.03 (95% CI: 0.87, 1.21). The relative risks of a relationship between PM2.5 and lung cancer incidence and mortality were 1.08 (95% CI: 1.03, 1.12) and 1.11 (95% CI: 1.05, 1.18), respectively. These findings will provide some evidence for policy makers and public health practitioners worldwide.

Stenting with pcARMS compared with standard ucSEMS reduces risk of ascending cholangitis and has longer stent patency, but does not increase patient survival. Chictr.org. number, ChiCTR-TRC-11001800.

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Insufflation with CO2 in colonoscopy could decrease abdominal discomfort during and following the procedure, without any additional adverse reactions, warranting routine clinical use.