Background Studies have suggested sex differences in the mortality rate associated with diabetes. We conducted a meta-analysis to estimate the relative effect of diabetes on the risk of all-cause, cancer, cardiovascular disease (CVD), infectious disease, and respiratory disease mortality in women compared with men. Methods Studies published from their inception to April 1, 2018, identified through a systematic search of PubMed and EMBASE and review of references. We used the sex-specific RRs to derive the women-to-men ratio of RRs (RRR) and 95% CIs from each study. Subsequently, the RRR for each outcome was pooled with random-effects meta-analysis weighted by the inverse of the variances of the log RRRs. Results Forty-nine studies with 86 prospective cohorts met the inclusion criteria and were eligible for analysis. The pooled women-to-men RRR showed a 13% greater risk of all-cause mortality associated with diabetes in women than in men (RRR 1.13, 95% CI 1.07 to 1.19; P < 0.001). The pooled multiple-adjusted RRR indicated a 30% significantly greater excess risk of CVD mortality in women with diabetes compared with men (RRR 1.30, 95% CI 1.13 to 1.49; P < 0.001). Compared with men with diabetes, women with diabetes had a 58% greater risk of coronary heart disease (CHD) mortality, but only an 8% greater risk of stroke mortality (RRR CHD 1.58, 95% CI 1.32 to 1.90; P < 0.001; RRR stroke 1.08, 95% CI 1.01 to 1.15; P < 0.001). However, no sex differences were observed in pooled results of populations with or without diabetes for all-cancer (RRR 1.02, 95% CI 0.98 to 1.06; P = 0.21), infectious (RRR 1.13, 95% CI 0.90 to 1.38; P = 0.33), and respiratory mortality (RRR 1.08, 95% CI 0.95 to 1.23; P = 0.26). Conclusions Compared with men with the same condition, women with diabetes have a 58% and 13% greater risk of CHD and all-cause mortality, respectively, although there was a significant heterogeneity between studies. This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention. Electronic supplementary material The online version of this article (10.1186/s12916-019-1355-0) contains supplementary material, which is available to authorized users.

Purpose: To ascertain whether sex differences exist in the relationship between marital status and cardiovascular diseases (CVD), coronary heart disease (CHD), cancer and all-cause mortality in the general population and to explore the potential effect of age, location, the duration of follow-up and publication years on these outcomes. Methods: A systematic search was performed in PubMed and EMBASE from inception through to April 2018 and review of references to obtain sex-specific relative risks and their 95% confidence intervals. These were used to derive the women-to-men ratio of RRs (RRR) and 95% CI for each study. RRs and RRRs for each outcome were then pooled using random effects inverse-variance weighted meta-analysis. Results: Twenty-one studies with 7,891,623 individuals and 1,888,752 deaths were included in the meta-analysis. Compared with married individuals, being unmarried was significantly associated with all-cause, cancer, CVD and coronary heart disease mortalities for both sexes. However, the association with CVD and all-cause mortality was stronger in men. Being divorced/separated was associated with a higher risk of all-cause mortality in men and a stronger risk of cancer and CVD mortality. The pooled ratio for women versus men showed 31 and 9% greater risk of stroke mortality and all-cause mortality associated with never married in men than in women. Conclusions: Being unmarried conferred higher risk of stroke and all-cause mortality for men than women. Moreover, divorced/separated men had higher risk of cancer mortality and CVD mortality. Further studies are warranted to clarify the biological, behavioral, and/or social mechanisms involved in sex differences by these associations.

The mammalian skeleton is a metabolically active organ that continuously undergoes bone remodeling, a process of tightly coupled bone resorption and formation throughout life. Recent studies have expanded our knowledge about the interactions between cells within bone marrow in bone remodeling. Macrophages resident in bone (BMMs) can regulate bone metabolism via secreting numbers of cytokines and exosomes. This review summarizes the current understanding of factors, exosomes, and hormones that involved in the communications between BMMs and other bone cells including mensenchymal stem cells, osteoblasts, osteocytes, and so on. We also discuss the role of BMMs and potential therapeutic approaches targeting BMMs in bone remodeling related diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma.

Heterotopic ossification (HO) is defined as the occurrence of extraskeletal bone in soft tissue. Although this pathological osteogenesis process involves the participation of osteoblasts and osteoclasts during the formation of bone structures, it differs from normal physiological osteogenesis in many features. In this article, the primary characteristics of heterotopic ossification are reviewed from both clinical and basic research perspectives, with a special highlight on the influence of mechanics on heterotopic ossification, which serves an important role in the prophylaxis and treatment of HO.

miR‐134 has been shown to be associated with angiogenesis and the progression of osteosarcoma. This study further assessed the effects of miR‐134 expression on osteosarcoma cell migration, invasion, and metastasis in vitro and in a nude mouse xenograft model, exploring the underlying molecular events. Luciferase reporter assays revealed that miR‐134 directly targets the 3′‐UTRs of MMP1 and MMP3 to reduce their expression in osteosarcoma cells. In conclusion, overexpression of miR‐134 suppresses osteosarcoma cell invasion and metastasis through the inhibition of MMP1 and MMP3 expression. We propose miR‐134 as an attractive novel therapeutic target for the treatment of osteosarcoma.

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Because of the modest response rate after surgery and chemotherapy, treatment of osteosarcoma (OS) remains challenging due to tumor recurrence and metastasis. miR-135a has been reported to act as an anticarcinogenic regulator of several cancers. However, its expression and function in osteosarcoma remain largely unknown. Here, we reported that abridged miR-135a expression in OS cells and tissues, and its expression is inversely correlated with the expression of BMI1 and KLF4, which are described as oncogenes in several cancers. Ectopic expression of miR-135a inhibited cell invasion and expression of BMI1 and KLF4 in OS cells. In vivo investigation confirmed that miR-135a acts as a tumor suppressor in OS to inhibit tumor growth and lung metastasis in xenograft nude mice. BMI1 and KLF4 were revealed to be direct targets of miR-135a, and miR-135a had a similar effect as the combination of si-BMI1 and si-KLF4 on inhibiting tumor progression and the expression of BMI1 and KLF4 in vivo. Altogether, our results demonstrate that the targeting of BMI1/KLF4 with miR-135a may provide an applicable strategy for exploring novel therapeutic approaches for OS.