Recent advances have highlighted profound roles of FOXO transcription factors, especially FOXO1, in bone development and remodeling. The regulation of bone development by FOXOs seems to be stage-specific or context dependent. FOXOs promote maintenance and differentiation of early progenitors of the osteoblast lineage and repress proliferation of committed osteoblast precursors; FOXO1 is vital for osteocyte survival. Considering the versatile roles played by FOXOs in bone development and tumorigenesis, it is plausible that FOXO1, the main FOXO in bone with a non-redundant role, might have influence on osteosarcoma (OS) oncogenesis. Indeed, recent results have implicated that FOXO1 has a tumor-suppressing role in OS. In the present study, we found that FOXO1 expression was generally low or absent in OS, with a minority of cases having moderate expression. Whole-genome sequencing (WGS) revealed that the FOXO1 locus was frequently involved in copy number variation and loss of heterozygosity in OS, indicating that chromosomal aberrations might be partially responsible for the heterogeneity in FOXO1 expression. FOXO1 activation in OS cell lines inhibited cancer cell survival, which can be attributed to modulation of target genes, including BIM and repressed Wnt/β-catenin signaling. FOXO1 inhibition promoted cell proliferation, enhanced colony formation and attenuated osteogenic differentiation of OS cell lines. To conclude, our results proved FOXO1 as a tumor suppressor in OS at least partially by suppression of the Wnt/β-catenin pathway.

Gastric cancer (GC) is one of the most common malignancies worldwide. Although some driver genes have been identified in GC, the molecular compositions of GC have not been fully understood. The development of next-generation sequencing (NGS) provides a high-throughput and systematic method to identify all genetic alterations in the cancer genome, especially in the field of mutation detection. NGS studies in GC have discovered some novel driver mutations. In this review, we focused on novel gene mutations discovered by NGS studies, along with some well-known driver genes in GC. We organized mutated genes from the perspective of related biological pathways. Mutations in genes relating to genome integrity (TP53, BRCA2), chromatin remodeling (ARID1A), cell adhesion (CDH1, FAT4, CTNNA1), cytoskeleton and cell motility (RHOA), Wnt pathway (CTNNB1, APC, RNF43), and RTK pathway (RTKs, RAS family, MAPK pathway, PIK pathway) are discussed. Efforts to establish a molecular classification based on NGS data which is valuable for future targeted therapy for GC are introduced. Comprehensive dissection of the molecular profile of GC cannot only unveil the molecular basis for GC but also identify genes of clinical utility, especially potential and specific therapeutic targets for GC.

The aim of this study was to evaluate the risk factors of peripheral arterial disease (PAD) and the relationship between ankle brachial index (ABI) and mortality from all-cause and cardiovascular disease (CVD) in Chinese patients with hypertension. The ABI cohort Study was designed to investigate risk factors of PAD and the relationship between ABI and mortality from all-cause and CVD in Chinese patients. ABI was identified at baseline by measuring systolic pressure at bilateral brachial and tibial arteries. Mortality surveillance was completed from November 2005 to January 2006. Among 3047 participants with hypertension at baseline, 839 (27.5%) were in the low-ABI group. Older age, female gender, higher serum level of triglycerides, lower serum level of high-density lipoprotein, a history of diabetes and a history of smoking were associated with low ABI. During the 13-month follow-up, there were 252 deaths, of which 100 died of CVD. Low ABI was associated with mortality from all-cause and CVD, whose adjusted relative risk was 1.619 (95% confidence interval 1.190-2.203) and 2.454 (1.531-3.933), respectively, in Cox regression models. The survival rate was significantly lower in the low-ABI group than in the normal-ABI group. This study demonstrated that low ABI was independently associated with a high risk of all-cause and CVD mortality in Chinese patients with hypertension. ABI should be promoted as an ideal tool to predict mortality in diabetic patients.

Background/Objectives: To evaluate the association between body mass index (BMI) and incident hypertension in a cohort of rural women in the Chinese population. Subjects/Methods: A population-based sample of 11 468 rural Chinese women aged X35 years and free from hypertension at baseline were followed-up from 2004-2006 to 2008. We calculated BMI from measured weight and height. Incident hypertension was defined as systolic blood pressure (BP) X140 mm Hg, diastolic BPX90 mm Hg or current use of antihypertensive medications. Results: During a median follow-up of 28 months, 2666 participants developed hypertension. Higher baseline BMI, even within the 'normal' range, was consistently associated with an increased risk of hypertension. Compared with participants in the lowest BMI quintile (18.5-21.1 kg/m 2 ), the multivariable-adjusted relative risks (95% confidence interval) of developing hypertension for women with a BMI of 21.2 to 22.4, 22.5 to 23.7, 23.8 to 25.4 and X25.4 kg/m 2 were 1.200 (1.058-1.361), 1.250 (1.100-1.419), 1.466 (1.291-1.666) and 1.785 (1.584-2.012), respectively (P for trend, o0.001). Further adjustment for baseline BP did not substantially alter these results. We found similar associations using other BMI categories and after excluding women with smoking history at baseline. The pattern of association also existed among old women (age X55 years). Conclusions:In this large cohort, we found a strong gradient association between higher BMI and increased risk of hypertension, even among older women within the normal BMI range. Clinicians should emphasize the importance of weight management for the primary prevention of hypertension in rural women in the Chinese population.