Qian Zhao

Aims: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome.Methods and results: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%).Conclusion: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

The Prospective Urban Rural Epidemiology (PURE) China Action on Spine and Hip status (CASH) study focused on the prevalence of osteoporosis and spinal fracture in China. The aim of the PURE CASH study is to determine the prevalence of osteoporosis and spinal fracture, and explore the potential relationship between spinal fracture and bone mineral density (BMD). This study is a prospective large-scale population study with a community-based sampling and recruitment strategy. The aim is to determine the prevalence of osteoporosis and vertebral fracture in this population, to evaluate the association between vertebral fractures and BMD values, and to assess the prediction power of BMD for incident fractures. Participants in the PURE CASH study are all from the PURE study in China, recruited from 12 centers in 7 Chinese provinces. The inclusion criteria are that participants should be aged more than 40 years and able to give informed consent. Exclusion criteria are pregnant women, individuals with metal implants in the lumbar spine, use of medications or the existence of any disease or condition known to have a major influence on BMD, and inability to give informed consent. A total of 3,457 participants undergo a quantitative computed tomography (QCT) scan of the upper abdomen. The scanning parameters are as follows: 120 kVp at all centers, mAs between 75 and 200, FOV 40 cm×40 cm. The BMD values of L1 to L3 are measured, and the average BMD calculated. The American College of Radiology QCT criteria for the diagnosis of osteoporosis is applied to determine the presence of osteoporosis. The scout view images of T4–L4 vertebrae are reviewed by two experienced radiologists for semi-quantification of vertebral fractures according to Genant’s method.

Context: Lung cancer still remains the leading cause of cancer-related mortality worldwide. Bone is one of preferred metastatic sites for lung cancer cells. So far, both accurate diagnosis and effective treatment of lung cancer bone metastases are difficult. Objective: This review aimed to evaluate roles of bone turnover markers (BTMs), microRNAs (miRNAs), dickkopf1 (DKK1) and insulin like growth factor binding protein 3 (IGFBP-3) in lung cancer bone metastases. Methods: We searched articles about these four biomarkers in lung cancer bone metastases mainly in PubMed. Result: The levels of bone specific alkaline phosphatase (BALP), cross-linked carboxy-terminal telopeptide of type-I collagen (ICTP) and N-terminal telopeptides of type-I collagen (NTX) were reported to be significantly increased in lung cancer patients with bone metastases. ALP, NTX and bone sialoprotein were thought to be associated with prognosis of lung cancer patients with bone metastases. MiRNA-335, miRNA-33a, miRNA-21, DKK1 and IGFBP-3 were revealed to be novel biomarkers in lung cancer bone metastases. Discussion and conclusion: Current researches have revealed that BTMs, miRNAs, DKK1 and IGFBP-3 may be useful in diagnosis, prognosis evaluation or treatment of lung cancer bone metastases. More studies about these biomarkers in lung cancer bone metastases are needed.

Background: Bone metastasis is a common complication of certain types of cancer, and unfortunately, it is still incurable to date. Immune system is a major defence against tumor cells and bone metastasis. However, the immunodeficient mouse models are widely used in most researches of bone metastasis, thereby excluding the regulatory roles of the immune system in bone metastasis. Objective: The aim was to provide a comprehensive overview on the cellular and molecular mechanisms by which immune cells interact with tumor cells and bone cells, as well as recent related patents. Method: We performed a literature search of PubMed database for the current knowledge on the interaction between bone metastasis and immune system. Recent related patents were obtained from World Intellectual Property Organization (WIPO) website. Results: Immune cells in the bone-tumor microenvironment include dentritic cells, monocytes/ macrophages, myeloid-derived suppressor cells, regulatory T cells, T helper cells, neutrophil, CD4+ T lymphocytes, CD8+cytotoxic T lymphocytes, and natural killer cells, et al. In addition to their well-known immunomodulatory function, recent studies revealed that immune cells could cooperate with tumor cells and bone cells to enhance bone metastasis and tumor progression. There are some patents targeting immune system to inhibit bone metastasis. Conclusion: Immune cells are instigated by tumor cells to enhance the occurrence and the development of bone metastasis. Taking full advantage of anti-tumor roles of immune cells may bring the promise of a possible cure for bone metastasis.

The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6^−/−) mice were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-computed tomography. Gene expression related to lipid and bone metabolisms was assayed with real-time quantitative polymerase chain reaction. Bone marrow cells from both genotypes were induced to differentiate into osteoblasts or osteoclasts, and treated with palmitic acid (PA). HFD increased the body weight and fat pad weight, and impaired lipid metabolism in both WT and IL6^−/− mice. The dysregulation of lipid metabolism was more serious in IL6^−/− mice. Trabecular bone volume fraction, trabecular bone number and trabecular bone thickness were significantly downregulated in WT mice after HFD than those in the RD (P < 0.05). However, these bone microstructural parameters were increased by 53%, 34% and 40%, respectively, in IL6^−/− mice than those in WT mice on the HFD (P < 0.05). IL6^−/− osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control and PA treatment group (P < 0.05). IL6^−/− mice showed significantly lower mRNA levels of PPARγ and leptin and higher mRNA levels of adiponectin in comparison with WT mice on HFD. In conclusion, these findings suggested that IL6 gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and bone metabolisms and could be a new potential therapeutic target for lipid metabolism disturbance-related bone loss. Abstract The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6^−/−) mice were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-computed tomography. Gene expression related to lipid and bone metabolisms was assayed with real-time quantitative polymerase chain reaction. Bone marrow cells from both genotypes were induced to differentiate into osteoblasts or osteoclasts, and treated with palmitic acid (PA). HFD increased the body weight and fat pad weight, and impaired lipid metabolism in both WT and IL6^−/− mice. The dysregulation of lipid metabolism was more serious in IL6^−/− mice. Trabecular bone volume fraction, trabecular bone number and trabecular bone thickness were significantly downregulated in WT mice after HFD than those in the RD (P < 0.05). However, these bone microstructural parameters were increased by 53%, 34% and 40%, respectively, in IL6^−/− mice than those in WT mice on the HFD (P < 0.05). IL6^−/− osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control and PA treatment group (P < 0.05). IL6^−/− mice showed significantly lower mRNA levels of PPARγ and leptin and higher mRNA levels of adiponectin in comparison with WT mice on HFD. In conclusion, these findings suggested that IL6 gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and bone metabolisms and could be a new potential therapeutic target for lipid metabolism disturbance-related bone loss.

Abstract: MicroRNAs (miRNAs) are a new class of small noncoding RNAs of 19–25 nucleotides that function as negative posttranscriptional gene regulators. MiRNAs hybridize to the 3’ untranslated region (UTR) of target mRNAs and repress translation or mediate mRNA cleavage. MiRNAs critically regulate tumorigenesis and progression by targeting oncogenes, tumor suppressor genes, or genes related to proliferation, angiogenesis, and apoptosis. Different tumor types and tumors at different stages exhibit unique miRNA profiles. MiRNAs show promise as potential biomarkers for cancer diagnostics, progression, and response to treatment. The role of miRNAs in promoting bone metastases is under investigated. We summarize recent findings on the mechanisms by which miRNAs may regulate bone metastatic spread of breast cancer, prostate cancer，lung cancer and multiple myeloma. We review similarities and differences in miRNA profiles that may explain the variety of molecular pathways underling metastatic spread to the skeleton in different cancers. Finally, we discuss the exciting potential of using miRNAs as diagnostics and therapeutic targets to reduce the risk of bone metastases in cancer, from the perspective of data provided by recent pre-clinical and clinical studies.

Lung cancer is the leading cause of malignancy-related mortality worldwide. Metastases, which account for 90% of lung cancer deaths, frequently target the skeleton, leading to rapid deterioration in quality of life and premature death. The molecular mechanism underlying this progression, especially the development of bone metastases, is largely unknown. MicroRNAs (miRNAs) are small, endogenous, noncoding RNAs that function as negatively posttranscriptional gene regulators. Changes in miRNAs, which may exhibit either oncogenic or tumor suppressive activity, are common in lung cancer. Over-expressed miRNAs may contribute to oncogenesis by down-regulating tumor suppressors, whereas the loss of selected miRNAs may negatively regulate oncogenes or factors related to tumorigenesis and progression. MiRNAs may activate or repress metastases. Specific miRNA expression profiles may correlate with the response in treatment. We summarize recent findings and patents in the pathological roles of miRNAs in the progression and bone metastases in lung cancer, and discuss the diagnostic and therapeutic options in the clinical management of lung cancer.