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Background: Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer.Methods: Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models.Results: 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p < 0.001). For patients diagnosed with cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p < 0.001].Conclusion: The prevalence of cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background: The 1980's economic boom has been associated with a rapid expansion of China's sex industry over the past three decades. Consequently, the spread of sexually transmitted infections (STIs) and hepatitis infections among female sex workers (FSW) has become an important public health issue in China. This study identifies prevalence and risks of hepatitis and STIs in Chinese FSWs.Method: Four electronic databases were searched for Chinese and English language peer-reviewed studies conducted between 01/2000-12/2011 that reported prevalence of hepatitis and STIs (excluding HIV) among Chinese FSW. Following the PRISMA guidelines, meta-analysis was used to estimate pooled prevalence and 95% confidence intervals for each infection.Result: Three hundred and thirty nine articles (34 in English and 305 in Chinese) investigating 603,647 FSWs in 29 Chinese provinces were included in this review. Over the period 2000-2011, the seroprevalence of active hepatitis B and hepatitis C among FSW were 10.7% (7.3-15.5%) and 1.0% (0.7-1.3%), respectively. The most prevalent STI was human papillomavirus (HPV, 27.0% [10.1-55.1%]), followed by herpes simplex virus-2 (HSV-2, 15.8% [11.7-20.9%]), chlamydia (13.7% [12.1-15.4%]), gonorrhoea (6.1% [5.3-7.0%]), syphilis (5.2% [4.8-5.7%]), genital warts (3.3% [2.5-4.2%]) and Trichomonas vaginitis (2.1% [1.5-24.2%]). Disease burden of both hepatitis and STI among FSW were concentrated in South Central and Southwest China. In particular, chlamydia and syphilis demonstrated a significant declining trend during the studied period (P < 0.05). Compared with the general Chinese population, FSW had significantly higher prevalence of all STIs except Trichomonas vaginitis. Further, compared to the general FSW population, HIV-positive FSW had significantly higher prevalence of syphilis, chlamydia, HSV-2 and Trichomonas vaginitis.Conclusion: Prevalence of hepatitis and STIs remained high and mostly stable among Chinese FSW over the period of 2000-2011. Targeted STI and hepatitis surveillance and interventions should be strengthened among Chinese FSWs, especially those who are HIV-positive. [ABSTRACT FROM AUTHOR]

Background: Green fluorescent protein (GFP) and its derivative fluorescent proteins (FPs) are among the most commonly used reporter systems for studying gene expression and protein interaction in biomedical research. Most commercially available FPs have been optimized for their oligomerization state to prevent potential structural constraints that may interfere with the native function of fused proteins. Other approach to reducing structural constraints may include minimizing the structure of GFPs. Previous studies in an enhanced GFP variant (EGFP) identified a series of deletions that can retain GFP fluorescence. In this study, we interrogated the structural plasticity of a UV-optimized GFP variant (GFPUV) to amino acid deletions, characterized the effects of deletions and explored the feasibility of rescuing the fluorescence of deletion mutants using folding-enhancing mutations. Methods: Transposon mutagenesis was used to screen amino acid deletions in GFP that led to fluorescent and nonfluorescent phenotypes. The fluorescent GFP mutants were characterized for their whole-cell fluorescence and fraction soluble. Fluorescent GFP mutants with internal deletions were purified and characterized for their spectral and folding properties. Folding-ehancing mutations were introduced to deletion mutants to rescue their compromised fluorescence. Results: We identified twelve amino acid deletions that can retain the fluorescence of GFPUV. Seven of these deletions are either at the N- or C- terminus, while the other five are located at internal helices or strands. Further analysis suggested that the five internal deletions diminished the efficiency of protein folding and chromophore maturation. Protein expression under hypothermic condition or incorporation of folding-enhancing mutations could rescue the compromised fluorescence of deletion mutants. In addition, we generated dual deletion mutants that can retain GFP fluorescence. Conclusion: Our results suggested that a "size-minimized" GFP may be developed by iterative incorporation of amino acid deletions, followed by fluorescence rescue with folding-enhancing mutations. [ABSTRACT FROM AUTHOR]

Background For more than 240 million chronic HBV carriers worldwide, effective therapeutic HBV vaccines are urgently needed. Recently, we demonstrated that autophagosomes were efficient antigens carriers and capable to cross-prime robust T-cell responses and mediate regression of multiple established tumors. Here we tested whether autophagosomes derived from HBV expressing cells could also function as a therapeutic vaccine. Methods We generated an autophagosome-based HBV vaccine from HBV-expressing hepatoma cells and examined its ability to induce polyvalent anti-HBV T-cell responses and therapeutic efficacy in mouse models that mimics acute and chronic HBV infection in human. Results When compared to the vaccine based on recombinant HBsAg, autophagosome-based HBV vaccine cross-primed multi-specific anti-HBV T-cell responses and significantly reduced HBV replication and HBcAg expression in livers of both acute and chronic mouse models. Therapeutic effect of this HBV vaccine depended on anti-HBV CD8+ effector T cells and associated with increased HBsAg and HBcAg specific IFN-γ producing T cells in the chronic mouse model. Conclusions These results indicated that autophagosome-based HBV vaccine could effectively suppress the HBV replication, clear the HBV infected hepatocytes, and break the HBV tolerance in mouse model. The potential clinical application of autophagosome-based HBV vaccine is discussed. [ABSTRACT FROM AUTHOR]

Hippocampal N-methyl-D-aspartate receptor (NMDAR) is required for spatial working memory. Although evidence from genetic manipulation mice suggests an important role of hippocampal NMDAR NR2B subunits (NR2BNMDARs) in spatial working memory, it remains unclear whether or not the requirement of hippocampal NR2BNMDARs for spatial working memory depends on the time of spatial information maintained. Here, we investigate the contribution of hippocampal NR2B-NMDARs to spatial working memory on delayed alternation task in T-maze (DAT task) and delayed matched-to-place task in water maze (DMP task). Our data show that infusions of the NR2BNMDAR selective antagonists, Ro25-6981 or ifenprodil, directly into the CA1 region, impair spatial working memory in DAT task with 30-s delay (not 5-s delay), but severely impair error-correction capability in both 5-s and 30-s delay task. Furthermore, intra-CA1 inhibition of NR2B-NMDARs impairs spatial working memory in DMP task with 10-min delay (not 30-s delay). Our results suggest that hippocampal NR2B-NMDARs are required for spatial working memory in long-delay task, whereas spare for spatial working memory in short-delay task. We conclude that the requirement of NR2B-NMDARs for spatial working memory is delay-dependent in the CA1 region. [ABSTRACT FROM AUTHOR]

Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM), while the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families, in DCM are unclear. To this end, 12 normal and 15 DCM heart samples were included in the present study. A murine cardiac remodeling model was induced by transverse aortic constriction (TAC). Real-time polymerase chain reaction was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated with TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end diastolic diameter and left ventricular ejection fraction. However, there was no obvious change in the expression levels of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A and SETD1B) between control and DCM hearts or remodeled mouse hearts. Furthermore, the dimethylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4 and EGR1, which might be regulated by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role in the pathological processes of DCM by regulating H3K4me2 and the expression of Smad3, GATA4 and EGR1. [ABSTRACT FROM AUTHOR]

Background: Green fluorescent protein (GFP) and its derivative fluorescent proteins (FPs) are among the most commonly used reporter systems for studying gene expression and protein interaction in biomedical research. Most commercially available FPs have been optimized for their oligomerization state to prevent potential structural constraints that may interfere with the native function of fused proteins. Other approach to reducing structural constraints may include minimizing the structure of GFPs. Previous studies in an enhanced GFP variant (EGFP) identified a series of deletions that can retain GFP fluorescence. In this study, we interrogated the structural plasticity of a UV-optimized GFP variant (GFP(UV)) to amino acid deletions, characterized the effects of deletions and explored the feasibility of rescuing the fluorescence of deletion mutants using folding-enhancing mutations., Methods: Transposon mutagenesis was used to screen amino acid deletions in GFP that led to fluorescent and nonfluorescent phenotypes. The fluorescent GFP mutants were characterized for their whole-cell fluorescence and fraction soluble. Fluorescent GFP mutants with internal deletions were purified and characterized for their spectral and folding properties. Folding-ehancing mutations were introduced to deletion mutants to rescue their compromised fluorescence., Results: We identified twelve amino acid deletions that can retain the fluorescence of GFP(UV). Seven of these deletions are either at the N- or C- terminus, while the other five are located at internal helices or strands. Further analysis suggested that the five internal deletions diminished the efficiency of protein folding and chromophore maturation. Protein expression under hypothermic condition or incorporation of folding-enhancing mutations could rescue the compromised fluorescence of deletion mutants. In addition, we generated dual deletion mutants that can retain GFP fluorescence., Conclusion: Our results suggested that a "size-minimized" GFP may be developed by iterative incorporation of amino acid deletions, followed by fluorescence rescue with folding-enhancing mutations.