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1.  Efficient Production of sTNFRII-gAD Fusion Protein in Large Quantity by Use of the Modified CHO-S Cell Expression System 
PLoS ONE  2014;9(10):e111229.
TNFα is one of the initial and important mediators to activate downstream signaling pathways by binding to trimerized TNFα receptors (TNFR), and thus is an ideal drug target for cancer therapy. Taking advantage of intrinsic homotimerization of the globular domain of adiponectin (gAD), we have developed a novel TNFα antagonist, the trimerized fusion protein named sTNFRII-gAD. However, our previously-used CHO expression system yielded less than 10 mg/L of sTNFRII-gAD. To produce large quantities of sTNFRII-gAD efficiently, we used a modified CHO-S cell expression system, which is based on a pMH3 vector with non-coding GC-rich DNA fragments for high-level gene expression. We obtained stable clones that produced 75 mg/L of sTNFRII-gAD in the 96-well plate, adapted the clones to 40 ml suspension serum-free batch culture, then optimized the culturing conditions to scale up the fed-batch culture in a 3 L shake-flask and finally in a 5 L AP30 bioreactor. We achieved a final yield of 52 mg/L of sTNFRII-gAD. The trimerized sTNFRII-gAD exhibited the higher affinity to TNFα with a dissociation constant (Kd) of 5.63 nM than the dimerized sTNFRII-Fc with a Kd of 13.4 nM, and further displayed the higher TNFα-neutralizing activity than sTNFRII-Fc (p<0.05) in a L929 cytotoxicity assay. Therefore, the strategy employed in this study may provide an efficient avenue for large-scale production of other recombinant proteins by use of the modified CHO-S cell expression system.
doi:10.1371/journal.pone.0111229
PMCID: PMC4207793  PMID: 25340707
2.  An update on overweight and obesity in rural Northeast China: from lifestyle risk factors to cardiometabolic comorbidities 
BMC Public Health  2014;14(1):1046.
Background
Not enough is known about the prevalence of overweight and obesity in rural China in the current decade. We aim to update our knowledge of the prevalence of obesity and its associated risk factors and comorbidities in a large population sample in rural Northeast China.
Methods
A population-based survey of 11,579 participants aged 35 years and older was conducted in rural areas of Liaoning Province during 2012–2013. Anthropometric measurements, information on health-related variables and blood biochemical indexes were collected by well-trained personnel.
Results
The prevalence of general obesity and overweight was found to be 7.8% and 37.2%, respectively. The overall prevalence of abdominal obesity was 15.1%. Female gender, ethnic minority, middle-school education and a family income of 5,000–20,000 CNY per year were found to be risk factors for general obesity, while older age, female gender, ethnic minority and longer sleep duration (>8 h/d) increased the risk of abdominal obesity, after adjusting for confounders. Overweight and obese participants had significantly higher risks to develop prehypertension, hypertension, high LDL-C and low HDL-C compared with normal weight participants, while abdominal obesity was associated with increased risks of diabetes and high TG after adjusted for multiple factors. Compared with participants with a normal BMI and no abdominal obesity, the participants classified as abdominally obese and normal BMI; as abdominally obese and overweight; and abdominally obese and generally obese each had a progressive increase in the odds of hypertension (OR: 1.961, 95% CI: 1.154 to 3.331, OR: 2.744, 95% CI: 2.126 to 3.541, and OR: 8.990, 95% CI: 5.858 to 13.795, respectively) and high TG (OR: 3.165, 95% CI: 2.183 to 4.588, OR: 3.980, 95% CI: 3.332 to 4.755, and OR: 4.340, 95% CI: 3.574 to 5.271, respectively).
Conclusions
The prevalence of obesity in rural Northeast China exhibited a remarkably increasing upwards trend. General and abdominal obesity were associated with different subtypes of cardiometabolic comorbidities, the combined effects of which on the comorbidities dramatically increased.
doi:10.1186/1471-2458-14-1046
PMCID: PMC4198624  PMID: 25293836
General obesity; Abdominal obesity; Prevalence; Risk factor; Comorbidities
3.  An update on the prevalence of metabolic syndrome and its associated factors in rural northeast China 
BMC Public Health  2014;14(1):877.
Background
The last study reported the prevalence of Metabolic Syndrome (MetS) in rural Northeast China was conducted approximately ten years ago. We aimed to update the data on the prevalence and epidemiological features of MetS in rural Northeast China.
Methods
This survey was conducted from July 2012 to August 2013. In this study, a total of 11,496 residents from the rural Northeast China were randomly selected and examined. MetS was defined according to the ATPIII-modified criteria. Data regarding the demographic and lifestyle characteristics and the blood biochemical indexes of these participants were collected by well-trained personnel.
Results
The prevalence of MetS was 39.0% and was more prevalent in women than in men (45.6% vs. 31.4%, P < 0.001). Elevated blood pressure was the most common metabolic disorder in both genders (71.7% in males and 63.3% in females). Only 11.2% and 9.6% of males and females, respectively, in this study had no metabolic disorders. Multivariate logistic regression, after adjusting for possible confounders, revealed the following factors that increased the risk of MetS: being female, older age, having more than one child, a family income of >20,000 CNY per year, longer sleep duration (>9 h/d), chronic disease status, frequent consumption of beans or bean products and frequent tea drinking. Completion of education through middle school, moderate physical activity and smoking were correlated with lower rates of MetS.
Conclusion
The prevalence of MetS was high in the rural areas of China, especially among females. In addition to some of the more conventional risk factors associated with MetS, including age, sex, annual income and educational status, we also found that having more than one child and frequent consumption of tea and beans were risk factors for MetS, while smoking was a common factor among those that did not have MetS in rural Northeast China.
doi:10.1186/1471-2458-14-877
PMCID: PMC4153886  PMID: 25159694
Metabolic syndrome; Prevalence; Risk factor; Hypertension
4.  L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness 
The Journal of General Virology  2013;94(Pt 7):1597-1607.
The fitness of non-nucleoside reverse transcriptase inhibitor (NNRTI) drug-resistant reverse transcriptase (RT) mutants of HIV-1 correlates with the amount of RT in the virions and the RNase H activity of the RT. We wanted to understand the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S viruses. We measured the amount of RT in virions and the polymerization and RNase H activities of mutant RTs compared to wild-type, K103N and G190S. We found that L100I, K101E and L74V did not change the polymerization or RNase H activities of K103N or G190S RTs. However, L100I and K101E reduced the amount of RT in the virions and subsequent addition of L74V restored RT levels back to those of G190S or K103N alone. We conclude that fitness changes caused by L100I, K101E and L74V derive from their effects on RT content.
doi:10.1099/vir.0.050914-0
PMCID: PMC3709637  PMID: 23535575
5.  The Prevalence and Risk Factors for Depression Symptoms in a Rural Chinese Sample Population 
PLoS ONE  2014;9(6):e99692.
Background
It is essential to understand how we can prevent and treat the epidemic of depression. Several studies have reported the prevalence of depressive symptoms in the urban population in China, but there is a lack of information regarding the prevalence of depression in rural populations.
Objective
To understand the prevalence of depression in a rural Chinese population and to analyze the risk factors for depression.
Methods
This study used a cross-sectional approach. A total of 11,473 subjects were surveyed and completed the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief scales. Living conditions, per capita income, marital status, and information about dietary health and chronic disease status were assessed.
Results
The prevalence of depressive symptoms in the population was 5.9%. The prevalence in women (8.1%) was higher compared with men (3.5%) and also increased with age. The per capita income level, amount of sleep obtained per day, education level, weekly consumption of meat and beans or bean products, salt intake, and chronic disease status were associated with depressive symptoms. The quality of life of individuals with a score less than 10 points on the PHQ-9 was significantly better compared with individuals with a score greater than 10.
Conclusion
The prevalence of depressive symptoms among rural population is higher than some southern cities in China. Dietary patterns may be an important risk factor linked to this disorder in the Chinese rural population.
doi:10.1371/journal.pone.0099692
PMCID: PMC4053343  PMID: 24919087
6.  CD4+ T-Cell Expansion Predicts Neutralizing Antibody Responses to Monovalent, Inactivated 2009 Pandemic Influenza A(H1N1) Virus Subtype H1N1 Vaccine 
The Journal of Infectious Diseases  2012;207(2):297-305.
Background. The ability of influenza vaccines to elicit CD4+ T cells and the relationship between induction of CD4+ T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination.
Methods. We tracked CD4+ T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4+ T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins.
Results. Our studies revealed that vaccination induced readily detectable CD4+ T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4+ T cells was most tightly correlated with the antibody response.
Conclusions. These results indicate that CD4+ T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4+ T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.
doi:10.1093/infdis/jis684
PMCID: PMC3532833  PMID: 23148285
influenza vaccines; pandemic H1N1 influenza; influenza virus; CD4+ T cells; cellular immune response; immunodominance; epitopes
7.  Statistical Estimation & Inference of Cell Counts from ELISPOT Limiting Dilution Assays 
The ELISPOT Assay is often used for cell count determination in immunological studies. Automated methods are needed to estimate cell concentrations from spot counts obtained from the assay. Three major distributions are assumed for observational cell counts. For each assumed distribution, individual least squares (LS)/maximum likelihood, and/or individual robust least squares (RLS) are applied for parameter estimation. Distributions of study endpoints (derived variables), defined as percentages of antigen-specific memory cell per total IgG, are investigated to provide a basis for hypothesis testing. We show, under some weak conditions, the distribution of endpoint estimates across subjects is approximately the same within a group. Thus the t-test or the Wilcoxon Rank Sum test can be applied to detect group differences. These methods are compared through simulations and application to real data.
doi:10.1080/10543406.2013.790645
PMCID: PMC3803109  PMID: 23786336
robust least squares; Wilcoxon Rank Sum test; limiting dilution assay
8.  B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination 
The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and ≥70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific antibody (Ab)-secreting cells and ≥4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.
doi:10.1128/CVI.00735-12
PMCID: PMC3675965  PMID: 23576673
9.  Poor Aerobic Fitness May Contribute to Cognitive Decline in HIV-infected Older Adults 
Aging and Disease  2013;4(6):311-319.
The HIV-infected older adult (HOA) community is particularly vulnerable to cognitive impairment. Previous studies in the general older adult population have reported that lower scores on tests of cognitive function often correlate negatively with aerobic fitness [5–7]. HIV-infected individuals have significantly reduced aerobic fitness and physical function compared to HIV-uninfected individuals. Determining important correlates of cognitive ability may be beneficial in not only detecting precursors to future cognitive impairments, but also target areas for interventions. The purpose of this study was to investigate the relationship between cognitive ability and aerobic fitness in HIV-infected older adults. We conducted a cross-sectional study of HOA on antiretroviral therapy (ART) >50 years of age. Domain specific cognitive function was assessed by means of a neuropsychological battery. Aerobic fitness (VO2peak) was assessed using a graded, progressive treadmill test. Thirty-seven HOA on ART (mean±SD: age 59±6 years, BMI 28±5, CD4 663±337 cells/ml, duration since HIV diagnosis 17±7 years; 81% males) completed the cognitive tests. Several domains of cognition were significantly associated with VO2peak by Spearman correlation analysis (p<0.05). By step-wise adjusted regression VO2peak was most frequently and significantly related to many cognitive domains such as verbal and visual memory, visual perception, and language (p<0.05). We found that participants with higher Vo2peak were less likely to have more severe forms of HIV-associated neurocognitive disorders (HAND) such as mild neurocognitive disorder (OR=0.65; p=0.01) and HIV-associated dementia (OR=0.64; p=0.0006). In HOA and in conclusion, aerobic fitness is related to cognitive performance on various tasks. The likelihood of cognitive impairment increased with lower fitness levels. Therefore, increased fitness may serve an important factor in maintenance of cognition and neural integrity for aging HIV-infected individuals. Future prospective and large scale studies are needed to evaluate the effect of fitness and vascular stiffness and function on cognition and brain structure among HOA.
doi:10.14336/AD.2013.0400311
PMCID: PMC3843648  PMID: 24307964
HIV; older adults; aerobic fitness; cognition
10.  High-Resolution Temporal Response Patterns to Influenza Vaccine Reveal a Distinct Human Plasma Cell Gene Signature 
Scientific Reports  2013;3:2327.
To identify sources of inter-subject variation in vaccine responses, we performed high-frequency sampling of human peripheral blood cells post-vaccination, followed by a novel systems biology analysis. Functional principal component analysis was used to examine time varying B cell vaccine responses. In subjects vaccinated within the previous three years, 90% of transcriptome variation was explained by a single subject-specific mathematical pattern. Within individual vaccine response patterns, a common subset of 742 genes was strongly correlated with migrating plasma cells. Of these, 366 genes were associated with human plasmablasts differentiating in vitro. Additionally, subject-specific temporal transcriptome patterns in peripheral blood mononuclear cells identified migration of myeloid/dendritic cell lineage cells one day after vaccination. Upstream analyses of transcriptome changes suggested both shared and subject-specific transcription groups underlying larger patterns. With robust statistical methods, time-varying response characteristics of individual subjects were effectively captured along with a shared plasma cell gene signature.
doi:10.1038/srep02327
PMCID: PMC3728595  PMID: 23900141
11.  Modeling health impact of global health programs implemented by Population Services International 
BMC Public Health  2013;13(Suppl 2):S3.
Background
Global health implementing organizations benefit most from health impact estimation models that isolate the individual effects of distributed products and services - a feature not typically found in intervention impact models, but which allow comparisons across interventions and intervention settings. Population Services International (PSI), a social marketing organization, has developed a set of impact models covering seven health program areas, which translate product/service distribution data into impact estimates. Each model's primary output is the number of disability-adjusted life-years (DALYs) averted by an intervention within a specific country and population context. This paper aims to describe the structure and inputs for two types of DALYs averted models, considering the benefits and limitations of this methodology.
Methods
PSI employs two modeling approaches for estimating health impact: a macro approach for most interventions and a micro approach for HIV, tuberculosis (TB), and behavior change communication (BCC) interventions. Within each intervention country context, the macro approach determines the coverage that one product/service unit provides a population in person-years, whereas the micro approach estimates an individual's risk of infection with and without the product/service unit. The models use these estimations to generate per unit DALYs averted coefficients for each intervention. When multiplied by program output data, these coefficients predict the total number of DALYs averted by an intervention in a country.
Results
Model outputs are presented by country for two examples: Water Chlorination DALYs Averted Model, a macro model, and the HIV Condom DALYs Averted Model for heterosexual transmission, a micro model. Health impact estimates measured in DALYs averted for PSI interventions on a global level are also presented.
Conclusions
The DALYs averted models offer implementing organizations practical measurement solutions for understanding an intervention's contribution to improving health. These models calculate health impact estimates that reflect the scale and diversity of program operations and intervention settings, and that enable comparisons across health areas and countries. Challenges remain in accounting for intervention synergies, attributing impact to a single organization, and sourcing and updating model inputs. Nevertheless, these models demonstrate how DALYs averted can be viably used by the global health community as a metric for predicting intervention impact using standard program output data.
doi:10.1186/1471-2458-13-S2-S3
PMCID: PMC3684543  PMID: 23902668
12.  Increase in IFNγ−IL-2+ Cells in Recent Human CD4 T Cell Responses to 2009 Pandemic H1N1 Influenza 
PLoS ONE  2013;8(3):e57275.
Human CD4 T cell recall responses to influenza virus are strongly biased towards Type 1 cytokines, producing IFNγ, IL-2 and TNFα. We have now examined the effector phenotypes of CD4 T cells in more detail, particularly focusing on differences between recent versus long-term, multiply-boosted responses. Peptides spanning the proteome of temporally distinct influenza viruses were distributed into pools enriched for cross-reactivity to different influenza strains, and used to stimulate antigen-specific CD4 T cells representing recent or long-term memory. In the general population, peptides unique to the long-circulating influenza A/New Caledonia/20/99 (H1N1) induced Th1-like responses biased toward the expression of IFNγ+TNFα+ CD4 T cells. In contrast, peptide pools enriched for non-cross-reactive peptides of the pandemic influenza A/California/04/09 (H1N1) induced more IFNγ−IL-2+TNFα+ T cells, similar to the IFNγ−IL-2+ non-polarized, primed precursor T cells (Thpp) that are a predominant response to protein vaccination. These results were confirmed in a second study that compared samples taken before the 2009 pandemic to samples taken one month after PCR-confirmed A/California/04/09 infection. There were striking increases in influenza-specific TNFα+, IFNγ+, and IL-2+ cells in the post-infection samples. Importantly, peptides enriched for non-cross-reactive A/California/04/09 specificities induced a higher proportion of Thpp-like IFNγ−IL-2+TNFα+ CD4 T cells than peptide pools cross-reactive with previous influenza strains, which induced more Th1 (IFNγ+TNFα+) responses. These IFNγ−IL-2+TNFα+ CD4 T cells may be an important target population for vaccination regimens, as these cells are induced upon infection, may have high proliferative potential, and may play a role in providing future effector cells during subsequent infections.
doi:10.1371/journal.pone.0057275
PMCID: PMC3603952  PMID: 23526940
13.  Differences in lifestyle behaviors, dietary habits, and familial factors among normal-weight, overweight, and obese Chinese children and adolescents 
Background
Pediatric obesity has become a global public health problem. Data on the lifestyle behaviors, dietary habits, and familial factors of overweight and obese children and adolescents are limited. The present study aims to compare health-related factors among normal-weight, overweight, and obese Chinese children and adolescents.
Methods
We conducted a cross-sectional study consisted of 4262 children and adolescents aged 5–18 years old from rural areas of the northeast China. Anthropometric measurements and self-reported information on health-related variables, such as physical activities, sleep duration, dietary habits, family income, and recognition of weight status from the views of both children and parents, were collected by trained personnel.
Results
The prevalence rates of overweight and obesity were 15.3 and 6.4%, respectively. Compared to girls, boys were more commonly overweight (17.5% vs. 12.9%) and obese (9.5% vs. 3.1%). Approximately half of the parents with an overweight or obese child reported that they failed to recognize their child’s excess weight status, and 65% of patients with an overweight child reported that they would not take measures to decrease their child’s body weight. Obese children and adolescents were more likely to be nonsnackers [odds ratio (OR): 1.348; 95% confidence interval (CI): 1.039–1.748] and to have a family income of 2000 CNY or more per month (OR: 1.442; 95% CI: 1.045–1.99) and less likely to sleep longer (≥7.5 h) (OR: 0.475; 95% CI: 0.31–0.728) than the normal-weight participants.
Conclusions
Our study revealed a high prevalence of overweight and obesity in a large Chinese pediatric population. Differences in sleep duration, snacking, family income, and parental recognition of children’s weight status among participants in different weight categories were observed, which should be considered when planning prevention and treatment programs for pediatric obesity.
doi:10.1186/1479-5868-9-120
PMCID: PMC3522535  PMID: 23031205
Overweight; Obesity; Children; Adolescents; Health-related factors
14.  Anergic Responses Characterize a Large Fraction of Human Autoreactive Naïve B Cells Expressing Low Levels of Surface IgM1 
B cell anergy represents an important mechanism of peripheral immunological tolerance for mature autoreactive B cells that escape central tolerance enforced by receptor editing and clonal deletion. While well documented in mice, the extent of its participation in human B cell tolerance remains to be fully established. In this study, we characterize the functional behavior of strictly defined human naïve B cells separated on the basis of their surface IgM (sIgM) expression levels. We demonstrate that cells with lower sIgM levels (IgMlo) are impaired in their ability to flux calcium in response to either anti-IgM or anti-IgD cross-linking, and contain a significantly increased frequency of autoreactive cells compared to naïve B cells with higher levels of sIgM. Phenotypically, in healthy subjects, IgMlo cells are characterized by the absence of activation markers, reduction of co-stimulatory molecules (CD19 and CD21) and increased levels of inhibitory CD22. Functionally, IgMlo cells display significantly weaker proliferation, impaired differentiation, and poor antibody production. In aggregate, the data indicates that hypo-responsiveness to BCR cross-linking associated with sIgM down-regulation is present in a much larger fraction of all human naïve B cells than previously reported, and is likely to reflect a state of anergy induced by chronic autoantigen stimulation. Finally, our results indicate that in SLE patients, naïve IgMlo cells display increased levels of CD95 and decreased levels of CD22, a phenotype consistent with enhanced activation of autoreactive naïve B cells in this autoimmune disease.
doi:10.4049/jimmunol.1001946
PMCID: PMC3095097  PMID: 21398610
Human B cells; anergy; tolerance
15.  Functionally Distinct Subpopulations of CpG-Activated Memory B Cells 
Scientific Reports  2012;2:345.
During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27lo subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27hi plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27lo and proliferating CD27hi subpopulations. Our data supported an alternative hypothesis, that CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation.
doi:10.1038/srep00345
PMCID: PMC3315693  PMID: 22468229
16.  Host Differences in Influenza-Specific CD4 T Cell and B Cell Responses Are Modulated by Viral Strain and Route of Immunization 
PLoS ONE  2012;7(3):e34377.
The antibody response to influenza infection is largely dependent on CD4 T cell help for B cells. Cognate signals and secreted factors provided by CD4 T cells drive B cell activation and regulate antibody isotype switching for optimal antiviral activity. Recently, we analyzed HLA-DR1 transgenic (DR1) mice and C57BL/10 (B10) mice after infection with influenza virus A/New Caledonia/20/99 (NC) and defined epitopes recognized by virus-specific CD4 T cells. Using this information in the current study, we demonstrate that the pattern of secretion of IL-2, IFN-γ, and IL-4 by CD4 T cells activated by NC infection is largely independent of epitope specificity and the magnitude of the epitope-specific response. Interestingly, however, the characteristics of the virus-specific CD4 T cell and the B cell response to NC infection differed in DR1 and B10 mice. The response in B10 mice featured predominantly IFN-γ-secreting CD4 T cells and strong IgG2b/IgG2c production. In contrast, in DR1 mice most CD4 T cells secreted IL-2 and IgG production was IgG1-biased. Infection of DR1 mice with influenza PR8 generated a response that was comparable to that in B10 mice, with predominantly IFN-γ-secreting CD4 T cells and greater numbers of IgG2c than IgG1 antibody-secreting cells. The response to intramuscular vaccination with inactivated NC was similar in DR1 and B10 mice; the majority of CD4 T cells secreted IL-2 and most IgG antibody-secreting cells produced IgG2b or IgG2c. Our findings identify inherent host influences on characteristics of the virus-specific CD4 T cell and B cell responses that are restricted to the lung environment. Furthermore, we show that these host influences are substantially modulated by the type of infecting virus via the early induction of innate factors. Our findings emphasize the importance of immunization strategy for demonstrating inherent host differences in CD4 T cell and B cell responses.
doi:10.1371/journal.pone.0034377
PMCID: PMC3311631  PMID: 22457834
17.  Viral Decay Rates are Similar in HIV-infected Patients with and without TB Coinfection during Treatment with an Efavirenz-based Regimen 
Viral decay rates during efavirenz-based therapy were compared between HIV-infected patients without (N=40) and with tuberculosis coinfection on concurrent antituberculous therapy (N=34). Phase 1 and II viral decay rates were similar in the two groups (P>0.05). Overall, concurrent antituberculous therapy did not reduce the efficacy of the HIV treatment.
Viral decay rates during efavirenz-based therapy were compared between human immunodeficiency virus (HIV)–infected patients without tuberculosis (n = 40) and those with tuberculosis coinfection who were receiving concurrent antituberculous therapy (n = 34). Phase I and II viral decay rates were similar in the 2 groups (P > .05). Overall, concurrent antituberculous therapy did not reduce the efficacy of the HIV treatment.
doi:10.1093/cid/ciq196
PMCID: PMC3060905  PMID: 21252140
18.  Succession and growth strategy of a spring microbial community from kezhou sinter in china 
The succession and growth strategy of a spring microbial community under earthquake action were investigated. The majority of pre-earthquake isolates belonged to the Gammaproteobacteria, including two numerically dominant Stenotrophomonas sp. RB25 and Acinetobacter sp. RB11 (r-strategists). The predominant post-earthquake isolates were Alphaproteobacteria, with Rhizobium sp. RA42 (K-strategists) being dominant among these organisms.
doi:10.1590/S1517-83822011000100005
PMCID: PMC3768905  PMID: 24031602
Growth strategy; Succession; Spring microbe; Earthquake
19.  B cell Responses to H5 influenza HA in Human Subjects Vaccinated with a Drifted Variant 
Vaccine  2009;28(4):907.
B cell responses after immunization with a drifted H5 influenza/A/Vietnam/1203/04 vaccine were characterized in the peripheral blood of human subjects primed with experimental recombinant H5 influenza A/Hong Kong/156/97 vaccine. Antibody secreting cells were assayed by ELISPOT against a panel of recombinant hemagglutinin and control proteins. Increased frequencies of H5 HA specific antibody secreting and memory B cells could be observed within 7 days of re-vaccination. Furthermore, these responses were cross-reactive to both H5 HA variants, but not H3 or avian H6 HA strains. These observations suggest prior vaccination against H5 influenza HA induces cellular immune responses that cross-react among drifted variants, without precluding a response to new, or existing HA strains.
doi:10.1016/j.vaccine.2009.11.002
PMCID: PMC2814950  PMID: 19932673
Influenza; B cell; hemagglutinin
20.  c-Fos as a Proapoptotic Agent in TRAIL-Induced Apoptosis in Prostate Cancer Cells 
Cancer research  2007;67(19):9425-9434.
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)/Apo-2L promotes apoptosis in cancer cells while sparing normal cells. Although many cancers are sensitive to TRAIL-induced apoptosis, some evade the proapoptotic effects of TRAIL. Therefore, differentiating molecular mechanisms that distinguish between TRAIL-sensitive and TRAIL-resistant tumors are essential for effective cancer therapies. Here, we show that c-Fos functions as a proapoptotic agent by repressing the antiapoptotic molecule c-FLIP(L). c-Fos binds the c-FLIP(L) promoter, represses its transcriptional activity, and reduces c-FLIP(L) mRNA and protein levels. Therefore, c-Fos is a key regulator of c-FLIP(L), and activation of c-Fos determines whether a cancer cell will undergo cell death after TRAIL treatment. Strategies to activate c-Fos or inhibit c-FLIP(L) may potentiate TRAIL-based proapoptotic therapies.
doi:10.1158/0008-5472.CAN-07-1310
PMCID: PMC2941899  PMID: 17909052
21.  Expressions of HIV-Related Stigma among Rural-to-Urban Migrants in China 
AIDS Patient Care and STDs  2008;22(10):823-831.
Abstract
In China, HIV-related stigma is considered as a formidable barrier in the combat against the HIV epidemic. There have been few qualitative investigations on HIV-related stigma in China, especially among a vulnerable population of rural-to-urban migrants. Based on 90 in-depth interviews conducted in 2002–2003 with rural-to-urban migrants in Beijing and Nanjing, China, this study examines the forms and expressions of HIV-related stigma from migrants' perspectives regarding HIV infection and individuals at risk of HIV infection. Consistent with the general framework on stigma, Chinese rural-to-urban migrants' attitudes toward HIV infected individuals take forms of denial, indifference, labeling, separation, rejection, status loss, shame, hopelessness, and fear. These stigmatizing attitudes were mainly derived from fears of AIDS contagion and its negative consequences, fears of being associated with the diseases, and culturally relevant moral judgments. In addition to universal AIDS stigma, both traditional Chinese culture and socially marginalized position of rural migrant population have contributed to culturally unique aspects of stigmatizing attitudes among rural-to-urban migrants. These multifaceted manifestations of HIV-related stigma suggest that HIV stigma reduction intervention needs to address multiple aspects of HIV stigma and stigmatization including personal, cultural, institutional, and structural factors.
doi:10.1089/apc.2008.0001
PMCID: PMC2929146  PMID: 18847389
22.  Can variation in HIV/STD-related risk be explained by individual SES? Findings from female sex workers in a rural Chinese county 
Low socioeconomic status (SES) has been linked to HIV and sexually transmitted disease (STD) at a macro level because the majority of new cases of HIV infection in the world have been reported in underdeveloped or developing countries. However, empirical data on the relationship between individual SES and HIV/STD related risk have been mixed. Employing quantitative data from 454 female sex workers, this study was designed to examine the profile of the study sample in terms of their individual SES, HIV/STD-related sexual risk across work locations with different social, cultural and economic conditions; and examine the relationship between work location and HIV-related risk behaviors, controlling for individual SES. We have shown in the current study that both SES and HIV/STD-related risk behaviors significantly differed by work location. However, the difference in individual SES was not sufficient to explain the difference of HIV/STD-related risk across the work locations. The findings underscore the need for effective prevention intervention efforts targeting female sex workers in rural area. Based on the findings, we also suggest that HIV/STD intervention efforts among female sex workers should take the social and cultural contextual factors of their working environment (and sexual risks) into consideration.
doi:10.1080/07399330701738382
PMCID: PMC2322857  PMID: 18350430
HIV/STD; socioeconomic status (SES); sexual risk; female sex workers; China
23.  Profile of female sex workers in a Chinese county: Does it differ by where they came from and where they work? 
World health & population  2007;9(1):46-64.
Since the 1980s, informal or clandestine sex work in the service or entertainment industry has spread from municipalities to small towns in most areas of China. Despite recognition of the important role of female sex workers in HIV and STD epidemics in China, limited data are available regarding their individual characteristics and social and environmental context of their work. Furthermore, most existing studies on commercial sex in China have been conducted in large cities or tourist attractions. Using data from 454 female sex workers in a rural Chinese county, the current study was designed to explore the individual profile of commercial sex workers and to examine whether the profile and sexual risk behavior differ by where the female sex workers came from and where they work. The sample in the current study was different from previous studies in a number of key individual characteristics. However, similar to previous studies, the sample in the current study were driven into commercial sex by poverty or limited employment opportunities, lived in a stressful life, were subject to sexual harassment and related violence, and engaged in a number of health-compromising behaviors including behaviors that put them at risk of HIV/STD infection and depression. The findings of the current study underscore the urgent needs for effective HIV/STD prevention intervention and mental health promotion program among female sex workers in China. The data in the current study suggest a strong association of individual profile with the economic conditions of work sites and residence status (in-province residency versus out-province residence) which suggests that such efforts must take the social and cultural contextual factors of their working environment (and sexual risks) into consideration.
PMCID: PMC2249564  PMID: 18270499
female sex workers; China; individual characteristics; sexual risk; HIV/AIDS; mental health
24.  HIV-Related Risk Factors Associated with Commercial Sex Among Female Migrants in China 
Data from 633 sexually experienced female migrants were analyzed to examine the sociodemographic and psychosocial factors and human immunodeficiency virus (HIV)-related behaviors associated with involvement in commercial sex. Six percent (40/633) of the participants reported having had sex for money. Compared with women who had not engaged in commercialsex, women who had sold sex were younger, less educated, and more likely to be unmarried. They were more likely to have engaged in HIV-related risk behaviors, such as becoming intoxicated with alcohol and using drugs. Among women who engaged in commercialsex, only 28% of them consistently used condoms during the last three episodes of sexualintercourse. Women who had ever engaged in commercialsex demonstrated greater depressive symptoms than those without such a history (p<.01). Female migrants, especially those engaging in commercial sex, were vulnerable to HIV/sexually transmitted diseases (STDs). Sexualrisk reduction and condom promotion are urgently needed among this population. Further studies are needed to examine the causal relationship between depression and HIV risk behaviors.
doi:10.1080/07399330590905585
PMCID: PMC1791013  PMID: 15804913
25.  Rural-to-Urban Migrants and the HIV Epidemic in China 
AIDS and behavior  2006;10(4):421-430.
China is the next probable frontier for the global HIV epidemic. Central to this anticipated growth of the epidemic is the nation’s new and growing population of rural-to-urban migrants. Although there are an estimated 120 million migrants, little information is available about their social and cultural context of their lives in urban areas and their HIV-related perceptions and behaviors. On the basis of the in-depth individual interviews conducted among 90 rural-to-urban migrants in 2 major Chinese cities, Beijing and Nanjing, this qualitative study was designed to explore these issues with a particular focus on their relevance to sexual transmission of HIV. The findings suggest an urgent need for HIV/STI prevention programs that address the cultural, social, and economic constraints facing the migrant population in China.
doi:10.1007/s10461-005-9039-5
PMCID: PMC1791012  PMID: 16421651
China; culture; HIV/STI; rural-to-urban migrants; sexuality

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