Accelerometer-measured physical activity and sedentary behavior in Chinese children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: To synthesize evidence on accelerometer-measured moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) levels of Chinese children and adolescents. STUDY DESIGN: This is both a systematic review and meta-analysis study. METHODS: Online databases were searched for studies published from January 2009 up to February 2019. These studies reported accelerometer-measured daily minutes of MVPA and/or SB among Chinese children and adolescents. Random-effects meta-analysis was used to separately pool the time spent in MVPA and SB. RESULTS: Of 4754 records, 20 studies were included in the meta-analysis. Sample sizes ranged from 96 to 2163. The meta-analysis showed that Chinese children and adolescents spent 41.11 min/day in MVPA and 529.83 min/day in SB averagely. Boys spent more time in MVPA compared with girls (P = 0.01). Children accumulated more MVPA time than adolescents (P = 0.05), and children spent less time in SB than adolescents (P = 0.05). Unlike weekdays, SB was lower on weekends (P = 0.02). There were significant differences in children and adolescents' MVPA time in regions (P < 0.001). CONCLUSIONS: MVPA level in Chinese children and adolescents is well below international recommendations, and their SB level is very high.

Clinical and pathologic predictors of central lymph node metastasis in papillary thyroid microcarcinoma: a retrospective cohort study.

OBJECTIVE: To identify the clinical and pathological predictors of central lymph node metastasis (CLNM) in patients with clinically lymph node-negative papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: Data pertaining to 541 clinically lymph node-negative PTMC patients who underwent thyroid surgery at the Shanghai General Hospital between January 2010 and December 2013 were retrospectively analyzed. According to histopathological evidence of central lymph node involvement, patients were divided into central lymph node metastasis (CLNM)-positive and CLNM-negative groups; risk factors for CLNM were identified statistically. RESULTS: LNM was found in 148 (27.4%) patients. Gender (P = 0.002), age (P < 0.001), tumor size (P < 0.001), multifocality (P < 0.001), and extrathyroidal extension (P < 0.001) were significantly different between CLNM-positive and CLNM-negative groups. On multivariate analyses, male sex (odds ratio [OR] = 2.656), age <45 years (OR = 4.184), tumor size >0.575 cm (OR = 2.105), gross extrathyroidal extension (OR = 14.605) and multifocality (OR = 2.084) were independent risk factors for CLNM. Among patients who did not have any of these five risk factors, only 3.9% were found to have CLNM. CONCLUSIONS: A relatively high prevalence of CLNM was observed in patients with clinically lymph node-negative PTMC. CLNM was associated with male sex, younger age, larger tumor size, extrathyroidal extension and multifocal PTMC.

Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1.

Histone deacetylase (HDAC) inhibitors (HDACi) cause cancer cell growth arrest and/or apoptosis in vivo and in vitro. The HDACi suberoylanilide hydroxamic acid (SAHA) is in phase I/II clinical trials showing significant anticancer activity. Despite wide distribution of HDACs in chromatin, SAHA alters the expression of few genes in transformed cells. p21(WAF1) is one of the most commonly induced. SAHA does not alter the expression of p27(KIPI), an actively transcribed gene, or globin, a silent gene, in ARP-1 cells. Here we studied SAHA-induced changes in the p21(WAF1) promoter of ARP-1 cells to better understand the mechanism of HDACi gene activation. Within 1 h, SAHA caused modifications in acetylation and methylation of core histones and increased DNase I sensitivity and restriction enzyme accessibility in the p21(WAF1) promoter. These changes did not occur in the p27(KIPI) or epsilon-globin gene-related histones. The HDACi caused a marked decrease in HDAC1 and Myc and an increase in RNA polymerase II in proteins bound to the p21(WAF1) promoter. Thus, this study identifies effects of SAHA on p21(WAF1)-associated proteins that explain, at least in part, the selective effect of HDACi in altering gene expression.

Acetylation of a specific promoter nucleosome accompanies activation of the epsilon-globin gene by beta-globin locus control region HS2.

On stably replicating episomes, transcriptional activation of the epsilon-globin promoter by the beta-globin locus control region HS2 enhancer is correlated with an increase in nuclease sensitivity which is limited to the TATA-proximal nucleosome (N1). To elucidate what underlies this increase in nuclease sensitivity and the link between chromatin modification and gene expression, we examined the nucleoprotein composition and histone acetylation status of transcriptionally active and inactive promoters. Micrococcal nuclease digestion of active promoters in nuclei released few nucleosome-like nucleoprotein complexes containing N1 sequences in comparison to results with inactive promoters. We also observed that N1 DNA fragments from active promoters are of a subnucleosomal length. Nevertheless, chromatin immunoprecipitation experiments indicate that histones H3 and H4 are present on N1 sequences from active promoters, with H3 being dramatically hyperacetylated compared with that from inactive promoters and vector sequences. Strikingly, H3 in the adjacent upstream nucleosome (N2) does not appear to be differentially acetylated in active and inactive promoters, indicating that the nucleosome modification of the promoter that accompanies transactivation by HS2 is highly directed and specific. However, global acetylation of histones in vivo by trichostatin A did not activate transcription in the absence of HS2, suggesting that HS2 contributes additional activities necessary for transactivation. N1 sequences from active promoters also contain reduced levels of linker histone H1. The detection of a protected subnucleosomal sized N1 DNA fragment and the recovery of N1 DNA sequences in immunoprecipitations using anti-acetylated H3 and H4 antibodies argue that N1 is present, but in an altered conformation, in the active promoters.

Function of GATA transcription factors in hydroxyurea-induced HEL cells.

HEL cells, a human erythroleukemia cell line, mainly express the fetal (gamma) globin gene and trace amount of the embryonic (epsilon) globin gene, but not adult (beta) globin gene. Here we show that hydroxyurea (HU) can induce HEL cells to express adult (beta) globin gene and lead these cells to terminal differentiation. Results showed in Gel mobility shift assays that GATA factors could specifically bind to the regulatory elements of human beta-globin gene, including the proximal regulatory element (the beta-promoter) and the distal regulatory elements (the DNase I hypersensitive sites in the LCR, HS2-HS4 core sequences). However, the DNA binding patterns of GATA factors were quite different between HU-induced and uninduced HEL cells. Western-blot analysis of nuclear extracts from both the uninduced and HU-induced HEL cells revealed that the level of GATA-2 transcription factor decreased, whereas the level of GATA-1 transcription factor increased following the time of hydroxyurea induction. Furthermore, using RT-PCR analysis the expression of human beta-globin gene in HU-induced HEL cells could be blocked again when HEL cells were incubated in the presence of antisense oligonucleotides for hGATA-1, suggesting that the upregulation of hGATA-1 transcription factor might be critical for the expression of human beta-globin gene in HU-induced HEL cells.

STAT1 is involved in signal transduction in the EPO induced HEL cells.

Erythropoietin (EPO) is the major regulator of mammalian erythropoisis, which stimulates the growth and differentiation of hematopoietic cells through interaction with its receptor (EPO-R). Here we use HEL cells (a human erythro-leukemia cell line) as a model to elucidate the pathway of signal transduction in the EPO-induced HEL cells. Our data show that the EPOR (EPO receptor) on the surface of HEL cells interacts with the Janus tyrosine protein kinase (Jak2) to transduce intracellular signals through phosphorylation of cytoplasmic proteins in EPO-treated HEL cells. Both STAT1 and STAT5 in this cell line are tyrosine-phosphorylated and translocated to nucleus following the binding of EPO to HEL cells. Furthermore, the binding of both STAT1 and STAT5 proteins to specific DNA elements (SIE and PIE elements) is revealed in an EPO-dependent manner. Our data demonstrate that the pathway of signal transduction following the binding of EPO to HEL cells is similar to immature erythroid cell from the spleen of mice infected with anemia strain of Friend virus.

The apoptosis of HEL cells induced by hydroxyurea.

Hydroxyurea has been used to synchronize cultured cells to S-phase and used to treat patients with sickle-cell anemia. Recently, we found that hydroxyurea can induce the apoptosis of HEL (human erythroleukemia) cells. The induced HEL cells showed ultrastructurally chromatin condensation with regular crescents at the nuclear edges and apoptotic bodies. However, the cells of K562, another human erythroleukemia cell line, did not show such morphological changes. Under fluoroscope, the HEL cells after induction often displayed a clear reduction in nuclear diameter and nuclear chromatin cleavage and condensation and the presence of nuclear ring and apoptotic bodies. Analysis with flow cytometry showed that the percentage of apoptotic cells is about 30-40% after HEL cells were induced by hydroxyurea for 3 days. DNA ladder can be observed by electrophoretic analysis.

[The role of hydroxyurea in globin gene expression and cell differentiation of human erythroleukemia cell line].

The HEL cells, a human erythroleukemia cell line, express mainly the fetal globin gene and small amount of the embryonic (epsilon) globin gene, but not the adult (beta) globin gene. Hydroxyurea, a small organic compound, has been successfully used to treat sickle cell anemia and beta-thalessaemia. Our data demonstrated that the growth rate of HEL cell proliferation was inhibited by different doses of hydroxyurea (from 50 mumol/L to 200 mumol/L). Using both routine RT-PCR and quantitative PCR analyses, we revealed that the expression of beta-globin gene was sharply activated and alpha-globin gene was almost completely silenced when HEL cells were induced for 3 or 5 days. Meanwhile, gamma-globin gene was expressed with no much difference between induced and uninduced HEL cells. We also demonstrated that the expression of GATA-1 and NF-E 2, which were two of the most important transcription factors in erythrocyte development, was activated about 3 folds in the induced cells. We suggested that the induction of GATA-1 and NF-E 2 expression by hydroxyurea might lead to activation of the adult beta-globin gene through some pathways of signal transduction, therefore, hydroxyurea might play a role to induce HEL cells to terminal differentiation.