[Show abstract][Hide abstract] ABSTRACT: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined.
EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients.
When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression.
During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.
[Show abstract][Hide abstract] ABSTRACT: Objective: To improve clinical testing excellence through a large scale training project targeting laboratory operators at China's county and township hospitals. Methods: The Chinese Society of Laboratory Medicine launched the "Clinical Laboratory Standards and Training Support Project" from 2010 to 2013. The project innovatively created a model of partnership between government, professional association, individual hospitals and other social forces. A survey before training was conducted in 445 county-hospital laboratories in 31 provinces. Six months after implementation, a sampling survey was conducted among 250 participating county hospitals in 9 provinces to assess the project. Results: From 2010 to 2013, the project had covered 31 provinces of China, and trained technologists from 3 570 hospitals. After training, the average pass rate of assessment examination increased to 83.7% compared with 16.2% before the training. 29.6% hospitals added new biochemistry parameters, and the number of hospital with new hematology, immunology, and microbiology parameters accounted for 24.4%, 21.2% and 16.4%, respectively. The internal quality control and external quality assessment items also increased significantly. Biochemistry increased most, reaching 12.8% and 10.0%, and microbiology also reached 4.4% and 2.8% respectively. Bio-safety management capacities were also enhanced. The number of hospital implementing bio-safety risk assessment increased from 41.2% to 76.4%. Conclusions This project helpfully fills an important technical gap of clinical testing in China's rural healthcare infrastructure. Through training, clinical laboratory operations has been standardized, and systems of internal quality control and external quality assessment are increasingly improved.
[Show abstract][Hide abstract] ABSTRACT: Importance:
Current antiretroviral therapy is very effective in suppressing active HIV-1 replication, but does not fully eliminate virally infected cells. The ability of HIV-1 to persist long-term despite suppressive antiretroviral combination therapy represents a perplexing aspect of HIV-1 disease pathogenesis, since most HIV-1 target cells are activated, short-lived CD4 T cells. This study suggests that CD4 T helper cells with Th1/Th17 polarization have a preferential role as a long-term reservoir for HIV-1 infection during antiretroviral therapy, possibly because these cells may imitate some of the functional properties traditionally ascribed to stem cells, such as the ability to persist for extremely long periods of time and to repopulate their own pool size through homeostatic self-renewal. These observations support the hypothesis that HIV-1 persistence is driven by small subsets of long-lasting stem cell-like CD4 T cells that may represent particularly promising targets for clinical strategies aiming at HIV-1 eradication and cure.
Journal of Virology 09/2015; DOI:10.1128/JVI.01595-15 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between the cognitive impairment and hippocampal morphological and functional change in HIV-seropositive patients.
30 HIV+ patients who complain of memory-decreasing and 15 healthy volunteers were recruited. Performances of learning and memory were assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). Bilateral hippocampal volume, ADC value, FA value and MR spectroscopy variables of bilateral hippocampus and parahippocampus gyrus was detected by 3.0 T MR scanner.
We found significant differences in the all cognitive outcomes but one between HIV+ and HIV-. There was a difference in the ADC value of left parahippocampus gyrus between mild-impairment group and severe-impairment group (p=0.018). We found differences in the Cho, Cho/Cr, NAA/Cr of left hippocampus (p=0.002; p=0.008; p=0.002) and the Cho/Cr of right parahippocampus gyrus (p=0.023) between HIV+ and HIV-, and in the MI of left hippocampus (p=0.003) and the Glx of right hippocampus (p<0.001) between mild-impairment group and severe-impairment group. We found significantly positive correlations between NAA/Cr of left hippocampus and outcomes of HVLT-R, BVMT-R. There were significantly negative correlations between ADC value of hippocampus, parahippocampus gyrus and outcomes of HVLT-R, BVMT-R, and between Cho, Cho/Cr of hippocampus, parahippocampus gyrus and outcomes of HVLT-R, BVMT-R.
The performance of verbal learning and visual memory was significantly decreased in HIV-1 seropositive patients. The cognitive impairment of HIV infection was associated with conductive function and metabolic changes of hippocampus and parahippocampus gyrus in this study.
[Show abstract][Hide abstract] ABSTRACT: In HIV disease course, the decline of peripheral CD4 T-cell count correlates with rapid disease progression. The supply of peripheral naive T cells by the thymus requires precursor T-cell proliferation within the thymus. In the setting of HIV-1 infection, when both naive and memory T cells are progressively depleted, the contribution of thymic dysfunction in CD4 depletion needs to be studied. Previous research has shown that thymic function may also be impaired in HIV-1 infection. However, it is inconclusive regarding whether this impairment occurred at the early time or during the chronic phase. In addition, the relationship between thymic dysfunction and disease progression remains unknown. In this study, we examined the thymic function in 65 HIV-infected individuals. Among them, 17 were in acute phase, 15 were in early chronic phase, 15 were in chronic phase with no ART (antiretroviral therapy), and 18 were on ART. We also included 11 uninfected individuals as controls. We measured the peripheral blood levels of T-cell receptor rearrangement excision circles and PTK7 and CD31 expressions for the frequency of circulating recent thymic emigrants. We observed that the 2 indicators of thymic function, sj/β-TREC and PTK7, seemed to be lower in the chronic infection group than those in the acute and early chronic groups. Both indicators returned to the normal level after ART. However, after 1-year follow-up of patients with early HIV-1 infection, rapid progressors (n = 4) had lower PTK7 and CD31 expressions than chronic progressors (n = 6).
[Show abstract][Hide abstract] ABSTRACT: Background
Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, comprehensive investigation to determine incidence and prevalence of HIV infections (both early and established) and their predictors.
Methods and findings
In a multi-center cross-sectional study with a prospective component, 4496 eligible, consenting (written) MSM were recruited (non-response=0.22%), interviewed and undergone tests for HIV (Wesern blot(WB) and BED HIV-1 capture enzyme immunoassay IgG captured EIA(BED-CEIA) were jointly used to determinealong with HIV early(recent) or/and established case differentiationinfection), syphilis and herpes simplex virus-2 (HSV-2), in seven cities of China (Shanghai, Nanjing, Changsha, Zhengzhou, Ji’nan, Shenyang and Kunming) between June 2012 and June 2013.
Majority participants were aged ≤35 years (77.52%), migrants (60.27%), never married (69.79%), receptive during anal sex (70.52%) %) and found partners mainly through internet (67.94%). Only 8.47% got circumcised, 27.85% did not use condom during last anal sex, 28.32% used recreational drugs and 15.46% reported anal bleeding post intercourse.
HIV prevalence was 9.9% ( [95% Confidence Intervals (CI) =4.0 %-13.913.9 %] %). Among HIV cases 41.89% were recently infected, with HIVand incidence was of 8.90/100 Person-Years (95%CI =7.62-10.17). Among HIV cases 41.89% were recently infected. Prevalence for HSV-2 and syphilis were 11.9512.50% and 8.47%, respectively. Among HIV cases 41.89% were recently infected.
Compared to respective reference groups, higher odds of recent acquisition of HIV was associated with sexual debut during 16-25 years (aOR=3.20, 95%CI =1.01-10.22), playing receptive role (aOR=2.62, 95%CI =1.38-3.08), having multiple male partners (aOR=1.54, 95%CI =1.12-2.13), recreational drug use (aOR=1.98, 95%CI =1.39-2.80), anal bleeding (aOR=1.73, 95%CI =1.14-2.60) and having syphilis (aOR=3.08, 95%CI =2.04-4.67) or HSV-2 (aOR=2.43, 95%CI =1.58-3.73).
High rate of early HIV infection is potentially resulting in progressive deterioration of the overall HIV situation epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having later sexual debut, receptive role, multiple partners, history of recreational drug use, syphilis or HSV-2 infection and anal bleeding seemed to be the need of the hour.
[Show abstract][Hide abstract] ABSTRACT: Aims: To evaluate the prevalence and associated factors of reduced bone mineral density (BMD) among antiretroviral therapy (ART) naive HIV-infected male patients in China. Methods: We compared BMD between HIV-infected male patients and healthy controls. Risk factors of reduced BMD were studied using multivariable linear regression. Results: Reduced BMD rate of chronic HIV infection patients was higher. HIV infection was independently associated with decreased BMD after adjusting for demographic factors. Older age, lower BMI and men who have sex with men (MSM) were revealed as the risk factors of lower BMD in HIV-infected male patients. Conclusion: Reduced BMD rate of HIV-infected patients was high. Policies are needed for prevention and treatment.
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies (GWASs) have revealed several genetic loci associated with HIV-1 outcome following infection (e.g., HLA-C at 6p21.33) in multi-ethnic populations with genetic heterogeneity and racial/ethnic differences among Caucasians, African-Americans, and Hispanics. To systematically investigate the inherited predisposition to modulate HIV-1 infection in Chinese populations, we performed GWASs in three ethnically diverse HIV-infected patients groups (i.e., HAN, YUN, and XIN, N = 538). The reported loci at 6p21.33 was validated in HAN (e.g., rs9264942, P = 0.0018). An independent association signal (rs2442719, P = 7.85 × 10(-7), HAN group) in the same region was observed. Imputation results suggest that haplotype HLA-B*13:02/C*06:02, which can partially account for the GWAS signal, is associated with lower viral load in Han Chinese. Moreover, several novel loci were identified using GWAS approach including the top association signals at 6q13 (KCNQ5, rs947612, P = 2.15 × 10(-6)), 6p24.1 (PHACTR1, rs202072, P = 3.8 × 10(-6)), and 11q12.3 (SCGB1D4, rs11231017, P = 7.39 × 10(-7)) in HAN, YUN, and XIN groups, respectively. Our findings imply shared or specific mechanisms for host control of HIV-1 in ethnically diverse Chinese populations, which may shed new light on individualized HIV/AIDS therapy in China.
[Show abstract][Hide abstract] ABSTRACT: The data from apparently healthy individuals with thalassemia has been demonstrated to have an effect on the reference intervals for the erythrocyte indices in areas with a high incidence of thalassemia.
Six clinical centers screened apparently healthy individuals using a questionnaire and a physical examination. Then, the qualified reference individuals were selected by hematological indices and a genotypic thalassemia diagnosis. Statistical comparisons were conducted for the erythrocyte reference intervals in the Chinese population with and without thalassemia. The constituent ratios and the mean (SD) of erythrocyte indices according to the thalassemia genotype were calculated. The relationship between the MCV values and the thalassemia genotype was also estimated.
4,636 reference individuals were included using hematological indices and genotypic thalassemia screening. The results of the erythrocyte reference intervals for individuals in Guangzhou with thalassemia demonstrated that the RBC, MCV, and MCH values significantly differed by gender compared with other regions (p < 0.01). In contrast, for individuals without thalassemia, the results tended to be similar and clinically acceptable. In addition, the results of the erythrocyte indices revealed significant differences among α-thalassemia patients, β-thalassemia patients, and the control group.
Apparently healthy individuals with thalassemia in the high prevalence zone of thalassemia could not be excluded by the questionnaire, physical examination or laboratory indices (Fe < 6 μmol/L, Hb < 90 g/L). The screening of genotypic thalassemia based on the MCV or MCH values to exclude unqualified individuals is the most effective way to obtain accurate and reliable reference intervals for the erythrocyte indices.
[Show abstract][Hide abstract] ABSTRACT: The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latent nuclear antigen LANA plays an essential role in viral episome maintenance. LANA also contributes to DNA replication and tumorigenesis during latency. Recent studies suggested that LANA was involved in regulation of SUMOylation which results in chromatin silencing. To examine the pleiotropic effects of LANA protein on host cell gene expression, we utilized MS analysis to identify cellular proteins associated with the SUMO-Interacting Motif of LANA (LANA(SIM) ). In addition to the 6 bands identified as substantially associated with LANA(SIM) , 151 proteins were positively identified by MS/MS analysis. Compared with previous proteomic analysis of the N- and C- truncated mutants of LANA (LANA(NC) ), our results revealed that a complex of specific proteins with relatively high SUMOylation and SIM motifs are associated with LANA(SIM) . Intriguingly, consistent with our previous report that identified KAP1 as a key component, the in-vitro SUMO-2 modified isoform has a substantially higher affinity with LANA(SIM) than the SUMO-1 modified isoform. Moreover, via cluster and pathway analysis, we proposed a hypothetical model for the LANA(SIM) regulatory circuit involving aberrant SUMOylation of cell cycle (particular mitotic), DNA unwinding and replication, and pre-mRNA/mRNA processing-related proteins. This study provides a SUMOylated and non-SUMOylated proteome profile of LANA(SIM) -associated complex, and facilitates our understanding that viral-mediated gene regulation through SUMOylation is important for KSHV persistence and pathogenesis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Co-signaling molecules have been demonstrated to regulate regulatory T cells' (Tregs) function during human immunodeficiency virus (HIV) infection. A recently reported co-signaling molecule called herpes virus entry mediator (HVEM), a member of the tumor necrosis factor receptor family, can both enhance and inhibit the immune response. HVEM was also reported to enhance the suppressive function of regulatory T cells in mice. However, it remains unknown whether HVEM can regulate Treg function in HIV-infected patients or whether HVEM affects HIV disease progression. In this study, we found that the blockage of the HVEM could weaken Tregs' suppressive activity to effector T cells (Teffs). HVEM expression is reduced during the asymptomatic phase of HIV infection and fairly predictive of the recovery of CD4+T-cells in response to highly active anti-retroviral therapy (HAART), more so than nadir CD4+T-cell count or viral load. Taken together, these findings demonstrate the importance of HVEM in relation to Treg function and HIV disease progression, which would have therapeutic implications and provide insight into the pathogenesis of acquired immune deficiency syndrome (AIDS).
Current HIV research 04/2015; 13(2):151-9. DOI:10.2174/1570162X1302150415110714 · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The expression of ATP-dependent efflux pump P-glycoprotein (P-gp) in cancer cells generally results in multidrug resistance (MDR) to chemotherapeutic drugs, which is the main cause of chemotherapy failure in cancer treatment. The intracellular drug levels could be increased by some MDR reversal agents that inhibited the drug efflux activity of P-gp. The synthesized DNA nucleic acids of G-quadruplex represent a novel and unique class of anti-cancer agents. While there was no report on the roles of DNA G-quadruplex oligonucleotides (GQ-ODNs) in the MDR reversal, the present study was performed to investigate the ability of synthesized GQ-ODNs to reverse P-gp-mediated MDR and its mechanism in paclitaxel (PTX)-resistant SKOV3 (SKOV3/PTX) cells and their sensitive cell lines SKOV3. The ability of GQ-ODNs to reverse drug resistance was evaluated by MTS assay. The results showed that GQ-ODNs can reverse PTX resistance effectively. The potential of GQ-ODNs as reversal agents was evaluated with the nude mice tumor xenograft model and showed that the co-administration of the GQ-ODNs and PTX had better effects and was also more evident than treatment with only PTX. The P-gp expression was assessed by the Western blot; it showed that SKOV3/PTX cells showed highly expressed P-gp protein, while their sensitive cells scarcely showed P-gp. The presence of GQ-ODNs efficiently decreased the P-gp expression, showing that GQ-ODNs could reverse P-gp-mediated MDR by decreasing the expression of P-gp. This study indicated that GQ-ODNs could effectively reverse P-gp-mediated PTX resistance by inhibiting the expression of P-gp and by the co-administration of GQ-ODNs and PTX that could increase the apoptosis of SKOV3/PTX cells. Thus, the synthesized GQ-ODNs may be a potential inhibitor to overcome drug resistance.
[Show abstract][Hide abstract] ABSTRACT: Complete blood count (CBC) reference intervals are important to diagnose diseases, screen blood donors, and assess overall health. However, current reference intervals established by older instruments and technologies and those from American and European populations are not suitable for Chinese samples due to ethnic, dietary, and lifestyle differences. The aim of this multicenter collaborative study was to establish CBC reference intervals for healthy Han Chinese adults.
A total of 4,642 healthy individuals (2,136 males and 2,506 females) were recruited from six clinical centers in China (Shenyang, Beijing, Shanghai, Guangzhou, Chengdu, and Xi'an). Blood samples collected in K2EDTA anticoagulant tubes were analyzed. Analysis of variance was performed to determine differences in consensus intervals according to the use of data from the combined sample and selected samples.
Median and mean platelet counts from the Chengdu center were significantly lower than those from other centers. Red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) values were higher in males than in females at all ages. Other CBC parameters showed no significant instrument-, region-, age-, or sex-dependent difference. Thalassemia carriers were found to affect the lower or upper limit of different RBC profiles.
We were able to establish consensus intervals for CBC parameters in healthy Han Chinese adults. RBC, HGB, and HCT intervals were established for each sex. The reference interval for platelets for the Chengdu center should be established independently.
PLoS ONE 03/2015; 10(3):e0119669. DOI:10.1371/journal.pone.0119669 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The HLA-A*30-B*13-C*06 haplotype is reported to be associated with slow disease progression in HIV-1-infected Northern Han Chinese, but the mechanism remains unknown.
Gag-specific T cell responses and gag sequencing were performed in nine B' clade HIV-1-infected HLA-A*30-B*13-C*06-positive slow progressors to understand HLA associated viral control.
IFN-γ ELISPOT assays were performed to determine the Gag-specific T cell responses and cross reactivity to variants peptides. Longitudinal HIV-1 gag sequencing was performed at clonal level.
The overlapping peptides (OLP)-48: RQANFLGKIWPSHKGRPGNF (RL42 Gag434-453); OLP-2: GQLDRWEKIRLRPGGKKKYR (RL42 Gag11-30); OLP-15: VQNLQGQMVHQPISPRTLNA (RL42 Gag135-154) and OLP-16: HQPISPRTLNAWVKVVEEKA (RL42 Gag144-163) were dominant in HLA-A*30-B*13-C*06-positive patients. A new epitope (HQPISPRTL (Gag144-152, HL9)) within OLP-15 and OLP-16 was identified. Results showed that strong cross reactive responses to multiple immunodominant peptides were associated with better clinical outcomes. In addition, efficient cross-recognition of HL9 autologous variants developed in patients was associated with high CD4 T-cell counts. However, two patients who had developed mutations to their dominant responses during the follow up experienced decrease in CD4 T-cell counts. It appears that Gag-specific T cell responses against one or more un-mutated epitopes or cross-recognition of autologous epitope variants contribute to slow disease progression in HLA-A*30-B*13-C*06-positive patients.
We conclude that a single "appropriate" Gag-specific T cell response appears to be sufficient to protect patients from disease progression. HLA-A*30-B*13-C*06-positive individuals benefited from having a choice of numerous immunodominant gag epitopes for T cells to react. The study offers new insight for future design of T cell based HIV-1 vaccine.
AIDS (London, England) 03/2015; 29(9). DOI:10.1097/QAD.0000000000000652 · 5.55 Impact Factor