Social Determinants of Community Health Services Utilization among the Users in China: A 4-Year Cross-Sectional Study

Background To identify social factors determining the frequency of community health service (CHS) utilization among CHS users in China. Methods Nationwide cross-sectional surveys were conducted in 2008, 2009, 2010, and 2011. A total of 86,116 CHS visitors selected from 35 cities were interviewed. Descriptive analysis and multinomial logistic regression analysis were employed to analyze characteristics of CHS users, frequency of CHS utilization, and the socio-demographic and socio-economic factors influencing frequency of CHS utilization. Results Female and senior CHS clients were more likely to make 3–5 and ≥6 CHS visits (as opposed to 1–2 visits) than male and young clients, respectively. CHS clients with higher education were less frequent users than individuals with primary education or less in 2008 and 2009; in later surveys, CHS clients with higher education were the more frequent users. The association between frequent CHS visits and family income has changed significantly between 2008 and 2011. In 2011, income status did not have a discernible effect on the likelihood of making ≥6 CHS visits, and it only had a slight effect on making 3–5 CHS visits. Conclusion CHS may play an important role in providing primary health care to meet the demands of vulnerable populations in China. Over time, individuals with higher education are increasingly likely to make frequent CHS visits than individuals with primary school education or below. The gap in frequency of CHS utilization among different economic income groups decreased from 2008 to 2011

Focus on vulnerable populations and promoting equity in health service utilization ––an analysis of visitor characteristics and service utilization of the Chinese community health service

Background Community health service in China is designed to provide a convenient and affordable primary health service for the city residents, and to promote health equity. Based on data from a large national study of 35 cities across China, we examined the characteristics of the patients and the utilization of community health institutions (CHIs), and assessed the role of community health service in promoting equity in health service utilization for community residents. Methods Multistage sampling method was applied to select 35 cities in China. Four CHIs were randomly chosen in every district of the 35 cities. A total of 88,482 visitors to the selected CHIs were investigated by using intercept survey method at the exit of the CHIs in 2008, 2009, 2010, and 2011. Descriptive analyses were used to analyze the main characteristics (gender, age, and income) of the CHI visitors, and the results were compared with that from the National Health Services Survey (NHSS, including CHIs and higher levels of hospitals). We also analyzed the service utilization and the satisfactions of the CHI visitors. Results The proportions of the children (2.4%) and the elderly (about 22.7%) were lower in our survey than those in NHSS (9.8% and 38.8% respectively). The proportion of the low-income group (26.4%) was apparently higher than that in NHSS (12.5%). The children group had the lowest satisfaction with the CHIs than other age groups. The satisfaction of the low-income visitors was slightly higher than that of the higher-income visitors. The utilization rate of public health services was low in CHIs. Conclusions The CHIs in China appears to fulfill the public health target of uptake by vulnerable populations, and may play an important role in promoting equity in health service utilization. However, services for children and the elderly should be strengthened

A Straightforward but Not Piecewise Relationship between Age and Lymph Node Status in Chinese Breast Cancer Patients

PURPOSE: To investigate the relationship between age and axillary lymph node (LN) involvement in Chinese breast cancer patients, and to replicate a recently identified piecewise relationship between age and LN involvement. METHODS: A dataset, consisting of 3,715 patients (with complete information on study variables) with operable breast cancer consecutively surgically treated between 1996 and 2006, was derived from the database of Shanghai Cancer Hospital. Univariate and multivariate logistic regression were employed to analyze the relationship between age and LN. We subsequently performed a similar analysis on another dataset including 1,832 consecutive patients treated between 2007 and 2008 to replicate our findings in the first dataset. RESULTS: A U-shaped relationship (previously observed in two European populations) between age and LN status failed to be replicated in our dataset of Chinese patients. Instead, we observed a linear rather than piecewise relationship. After multivariate adjustment, the linear relationship was still present. Moreover, the interaction between age and LN involvement was not modified by tumor size. The odds of LN involvement decreased by 1.5% for each year increase in age (OR 0.985, 95% CI 0.979-0.991, P<0.001). Breast cancer subtypes were also associated with LN status. Proportions of basal-like and ERBB2+ subtypes decreased with increasing age. The observations in the first dataset were successfully replicated in a second independent dataset. CONCLUSION: We confirmed a straightforward but not piecewise relationship between age and LN status in Chinese patients. The different pattern between Chinese and European elderly patients should be considered when making clinical decisions

Evidence for a common progenitor of epithelial and mesenchymal components of the liver

Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. The liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the liver fibrosis) in adult organ is yet unveiled. We show here that epithelial and mesenchymal liver cells (hepatocytes and HSCs) may arise from a common progenitor. Sca+ murine progenitor cells were found to coexpress markers of epithelial and mesenchymal lineages and to give rise, within few generations, to cells that segregate the lineage-specific markers into two distinct subpopulations. Notably, these progenitor cells, clonally derived, when transplanted in healthy livers, were found to generate epithelial and mesenchymal liver-specific derivatives (i.e. hepatocytes and HSCs) properly integrated in the liver architecture. These evidences suggest the existence of a 'bona fide' organ-specific meso-endodermal precursor cell, thus profoundly modifying current models of adult progenitor commitment believed, so far, to be lineage-restricted. Heterotopic transplantations, which confirm the dual differentiation potentiality of those cells, indicates as tissue local cues are necessary to drive a full hepatic differentiation. These data provide first evidences for an adult stem/precursor cell capable to differentiate in both parenchymal and non-parenchymal organ-specific components and candidate the liver as the instructive site for the reservoir compartment of HSC precursors as yet non-localized in the adult. © 2013 Macmillan Publishers Limited All rights reserved

Polymorphism rs4919510:C>G in Mature Sequence of Human MicroRNA-608 Contributes to the Risk of HER2-Positive Breast Cancer but Not Other Subtypes

BACKGROUND: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly affect the binding of microRNA to hundreds of target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR-608 alters breast cancer susceptibility. METHODS: The association of rs4919510:C>G with risk and pathologic features of breast cancer were investigated in two independent case-control studies, the first set including 1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive, and 148 triple-negative) and 1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500 hospital-based cancer-free controls. Odds ratios (ORs) were estimated by logistic regression. Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G were surveyed to reveal potential pathological mechanism. RESULTS: In the first set, although rs4919510:C>G was unrelated to breast cancer in general patients, variant genotypes (CG/GG) were specifically associated with increased risk of HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15). Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal-Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2-positive subgroup was validated in the second set (Bonferroni corrected P = 0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1 × 10(-4)). Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral-miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to HSF1 mRNA. CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2-positive breast cancer risk and tumor proliferation

Analysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm

Circadian rhythm is fundamental in regulating a wide range of cellular, metabolic, physiological, and behavioral activities in mammals. Although a small number of key circadian genes have been identified through extensive molecular and genetic studies in the past, the existence of other key circadian genes and how they drive the genomewide circadian oscillation of gene expression in different tissues still remains unknown. Here we try to address these questions by integrating all available circadian microarray data in mammals. We identified 41 common circadian genes that showed circadian oscillation in a wide range of mouse tissues with a remarkable consistency of circadian phases across tissues. Comparisons across mouse, rat, rhesus macaque, and human showed that the circadian phases of known key circadian genes were delayed for 4–5 hours in rat compared to mouse and 8–12 hours in macaque and human compared to mouse. A systematic gene regulatory network for the mouse circadian rhythm was constructed after incorporating promoter analysis and transcription factor knockout or mutant microarray data. We observed the significant association of cis-regulatory elements: EBOX, DBOX, RRE, and HSE with the different phases of circadian oscillating genes. The analysis of the network structure revealed the paths through which light, food, and heat can entrain the circadian clock and identified that NR3C1 and FKBP/HSP90 complexes are central to the control of circadian genes through diverse environmental signals. Our study improves our understanding of the structure, design principle, and evolution of gene regulatory networks involved in the mammalian circadian rhythm

Longitudinal seroepidemiologic study of the 2009 pandemic influenza A (H1N1) infection among health care workers in a children's hospital

<p>Abstract</p> <p>Background</p> <p>To probe seroepidemiology of the 2009 pandemic influenza A (H1N1) among health care workers (HCWs) in a children's hospital.</p> <p>Methods</p> <p>From August 2009 to March 2010, serum samples were drawn from 150 HCWs in a children's hospital in Taipei before the 2009 influenza A (H1N1) pandemic, before H1N1 vaccination, and after the pandemic. HCWs who had come into direct contact with 2009 influenza A (H1N1) patients or their clinical respiratory samples during their daily work were designated as a high-risk group. Antibody levels were determined by hemagglutination inhibition (HAI) assay. A four-fold or greater increase in HAI titers between any successive paired sera was defined as seroconversion, and factors associated with seroconversion were analyzed.</p> <p>Results</p> <p>Among the 150 HCWs, 18 (12.0%) showed either virological or serological evidence of 2009 pandemic influenza A (H1N1) infection. Of the 90 unvaccinated HCWs, baseline and post-pandemic seroprotective rates were 5.6% and 20.0%. Seroconversion rates among unvaccinated HCWs were 14.4% (13/90), 22.5% (9/40), and 8.0% (4/50) for total, high-risk group, and low-risk group, respectively. Multivariate analysis revealed being in the high-risk group is an independent risk factor associated with seroconversion.</p> <p>Conclusion</p> <p>The infection rate of 2009 pandemic influenza A (H1N1) in HCWs was moderate and not higher than that for the general population. The majority of unvaccinated HCWs remained susceptible. Direct contact of influenza patients and their respiratory samples increased the risk of infection.</p

Establishing Clonal Cell Lines with Endothelial-Like Potential from CD9(hi), SSEA-1(−) Cells in Embryonic Stem Cell-Derived Embryoid Bodies

BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL FINDINGS: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r(2) = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9(hi), SSEA-1(−) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA-1(−) cells that constituted 1%–10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r(2) = 0.95) and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs

Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study

Introduction: Vitamin D has been postulated to be involved in cancer prognosis. Thus far, only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results. Therefore, the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [25(OH)D] concentrations on overall survival and distant disease-free survival. Methods: We conducted a prospective cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50-74 years. Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years. Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors. Fractional polynomials were used to assess the true dose-response relation for 25(OH)D. Results: Lower concentrations of 25(OH)D were linearly associated with higher risk of death (hazard ratio (HR) = 1.08 per 10 nmol/L decrement; 95% confidence interval (CI), 1.00 to 1.17) and significantly higher risk of distant recurrence (HR = 1.14 per 10 nmol/L decrement; 95%CI, 1.05 to 1.24). Compared with the highest tertile (≥ 55 nmol/L), patients within the lowest tertile (< 35 nmol/L) of 25(OH)D had a HR for overall survival of 1.55 (95%CI, 1.00 to 2.39) and a HR for distant disease-free survival of 2.09 (95%CI, 1.29 to 3.41). In addition, the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood samples collected before start of chemotherapy but not for those of samples taken after start of chemotherapy (P for interaction = 0.06). Conclusions: In conclusion, lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients

Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility

Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7–induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0×10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk