[The impact of broadened diagnostic criteria on the prevalence of hypertension, hyperlipidemia and diabetes mellitus in China].

Objective: The burden of chronic disease has been continuously increasing in China since the early 1980s. Besides the worsening of risk factors, the change in diagnostic criteria is very likely an important explanation for the increase in the prevalence of hypertension, hyperlipidemia and diabetes mellitus, three commonest, major chronic conditions that can lead to major vascular events and deaths. This study aims to estimate the contribution of changes in diagnostic criteria to the increase in the prevalence of the three conditions in China. Methods: The data from two representative nation-wide surveys in China in 2002 and 2009, with 145 254 and 8 813 adults included respectively, were used to estimate the prevalence rate of the three conditions and the proportion attributable to the change in diagnostic criteria around year 2000. The new and old cutoff values for hypertension, hyperlipidemia, and hyperglycemia were 140/90 and 160/95 mmHg (1 mmHg=0.133 kPa), 5.7 and 6.2 mmol/L, and 7.0 and 7.8 mmol/L, respectively. The prevalence was standardized according to the distribution of age, sex and rural-urban residence of the 2000 national census of the country so as to compare between the old and new diagnostic criteria and project the situation for the entire country. Results: The standardized prevalence of hypertension, hyperlipidemia, and diabetes mellitus for the entire Chinese adult population in 2002 was 8.21%, 1.71% and 1.43% according to the immediate previous diagnostic criteria, and 19.18%, 3.53% and 2.66% according to the new criteria. In 2009, the prevalence was 11.89%, 9.34% and 4.29% according to the old criteria, and 24.78%, 18.36% and 6.55% according to the new criteria. The total cumulative prevalence of the three conditions was increased by 124% in 2002 and 95% in 2009 as a result of change in diagnostic criteria. Put it differently, the change in diagnostic criteria increased the number of the three conditions from 2002 to 2009 by approximately 359 million and could increase the annual drug costs by some 271 billion RMB if all the conditions are treated. The drug costs alone of treating all the three conditions could consume 56% of the total health budget of the Government in 2010. Conclusion: About half of the number of the three conditions is a result of the change in diagnostic criteria. These criteria were adopted from western populations, which are designed to meet the population need and suit healthcare resources available in these countries. It is important for China to consider the resources available and needs and values of the population in addition to the benefits, harms and costs of treatment in determining the cutoff values for defining these conditions for drug interventions.

KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation.

KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG islands and recruits the polycomb repressive complex 1. Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCF(KDM2B)) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF (SKP1-CUL1-F-box)/CRL1 substrates that promotes substrates binding to F-box, epidermal growth factor (EGF)-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF or accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations.

Effects of CD3McAb and rhIL-2 activated bone marrow on the killing and purging of leukemia cells.

We investigated the roles of CD3McAb and rhIL-2 activated bone marrow in the killing and purging of leukemia cells. Cytotoxicity of activated bone marrow was detected with MTT assay. CFU-GM level in activated bone marrow and the destruction of leukemia cells were measured using the semi-solid cell culture. Immune activation markers in activated bone marrow were detected by indirect immunofluorescence assay. Bone marrow activated by CD3McAb and rhIL-2 displayed significantly upregulated the killing and purging abilities on the leukemia cell line K562 and HL-60. Such effects were superior to that of bone marrow activated by rhIL-2 or CD3McAb alone (P < 0.05, P < 0.01). Activation by rhIL-2 and (or) CD3McAb exerted no obvious influence on CFU-GM level in bone marrow. Compared with bone marrow activated by rhIL-2 or CD3McAb alone, the synergistic effect of both CD3McAb+ and hIL-2 caused significant increase of CD3(+), CD8(+), CD19(+), CD25(+), CD38(+), and CD56(+) levels. Our study indicates that CD3McAb enhanced the killing and purging effects of rhIL-2 activated bone marrow on leukemia cells.