Risk factors and longitudinal changes of dyslipidemia among Chinese people living with HIV receiving antiretroviral therapy.

BACKGROUND: Antiretroviral therapy (ART) improved the prognosis of people living with human immunodeficiency virus (HIV) (PLWH). Life-long treatment is required in PLWH and is accompanied by various metabolic abnormalities in the disease course. Data about the epidemiology and the dynamic changes of dyslipidemia in PLWH receiving antiretroviral therapy were scarce in Asian countries. This study aimed to explore the risk factors of dyslipidemia and analyze the longitudinal changes of dyslipidemia among Chinese PLWH receiving HAART. METHODS: We conducted a longitudinal analysis of PLWH enrolled in two large multicenter clinical trials across China, and outpatients followed at the clinic of Peking Union Medical College Hospital. Demographic data and clinical parameters were collected. The risk factors and longitudinal changes in lipid profiles associated with HIV-1 infection were analyzed. The definition of dyslipidemia was made based on the National Cholesterol Education Program, Adult Treatment Panel (NCEP-ATP) III guidelines. RESULTS: A total of 1542 PLWH were included. The median follow-up was 6 years. At baseline, the concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.1 ± 0.91 mmol/L, 1.2 (interquartile ranges [IQR] 0.85-1.75) mmol/L, 1.1 ± 0.37 and 2.4 ± 0.76 mmol/L, respectively. The rate of hypercholesterolemia, hyperglyceridemia, high LDL-C, and low HDL-C were 10.18%, 26.39%, 9.08%, and 44.94%, respectively. The overall prevalence of dyslipidemia was 69.3%, which raised to 84.3% after antiretroviral therapy, substantially higher. CD4/CD8 ratio < 0.3 and viral load > 105 copies/mL were risk factors associated with any subtype of dyslipidemia. A negative correlation between CD8+CD38+ percentage and HDL-C concentration was found. The regimens including efavirenz (EFV) and tenofovir (TDF) showed better lipid profiles. Longitudinal analysis revealed that both the level and the percentage of abnormal TG and HDL-C occurred drastic change in the first 6 months after ART initiation (from 4.07 to 4.41, from 1.11 to 1.28mmol/L, from 26.39 to 31.1% and from 44.94 to 29.5%, respectively). CONCLUSIONS: The prevalence of dyslipidemia is high in PLWH and increases after ART, mainly represented as high TG and low HDL-C and associated with advanced stage of HIV-1 infection. The greatest changes in lipids occurred in the early stage after initiating ART therapy. The results suggest that dyslipidemia should be monitored and managed when starting ART.

Design, synthesis and antifreeze properties of biomimetic peptoid oligomers.

Ice crystals can cause great damage. The utilization of antifreeze agents is an efficient method to prevent or reduce ice crystal formation and growth. Synthetic antifreeze agents are toxic and have low efficiency, and natural antifreeze proteins suffer from high cost and low stability. Here, we have designed and synthesized a series of peptoid oligomers by mimicking the antifreeze protein structure, and the structure-property relationship was also studied. The reported peptoids here have excellent antifreeze properties and are nontoxic to cells. These novel peptoid materials have great potential to replace current commonly used antifreeze agents, such as dimethyl sulfoxide, and become a new generation of antifreeze agents applied in cryopreservation.

The pattern and magnitude of T cell subsets reconstitution during ten years of ART with viral suppression in HIV-infected patients.

BACKGROUND: The extent of immune reconstitution in human immunodeficiency virus (HIV) infected persons receiving long-term antiretroviral therapy (ART) with controlled viral load has been controversial. We studied the extent and speed of T cell subsets retrieval after long-term antiretroviral treatment. METHODS: 662 HIV-infected patients followed at least 2 years whose plasma HIV-1 RNA load <50 copies/mL were evaluated for longitudinal and functional phenotypic indices of immune restoration. Determinants of change in magnitude and importance of recovery have been evaluated using mixed linear regression models. RESULTS: Almost all robust immune restorations achieved occurred after 2-3 years of ART. The median CD4 lymphocyte count increased 449 cells/µl (IQR 303-604) from 226 cells/µl (IQR 83-336) at baseline during the third year (P < 0.001); CD4+T lymphocyte rises during the sixth and tenth years were not significant. Naive and memory CD4+T cells'reconstitution occurred in the sixth and eighth years of ART but no significant change thereafter. The change of CD45RA+Naïve and CD45RA-memory CD4+T cell reconstitution is different in baseline CD4+T cell counts <100 cells/µl group and in baseline CD4+T cell counts >100 cells/µl group. Activation antigen expression (CD38 or HLA-DR) on CD8 lymphocytes declined mostly during the first till second year, and after 4 years, activation antigen expression on patient lymphocytes showed no significant change. The proportion of CD4 cells expressing CD28 climbed during the first years and reached normal levels in the second year. CONCLUSIONS: Immune restoration was dependent on the capacity of immune system during the first 2-3 year of ART. But the significant change of CD4 and compartments of CD4+T cells could persist until 6-8 years. The pattern of CD38+CD8+, HLA-DR+CD8+, CD28+CD4+ T cells could quickly return to normal level and no significant change after sufficient time of ART. In general, the immune response compared to the baseline status may be the overall effect from the age and time of antiretroviral treatment.

Association between ERCC1 Gene Polymorphism (rs11615) and Colorectal Cancer Susceptibility: A Meta-Analysis of Medical Image Fusion and Safety Applications.

Colorectal cancer (CRC) is a malignant tumor of the colorectal mucosa epithelial tissue transformed. The fusion of data for medical imaging has become a central issue in such biomedical applications as image-guided surgery and radiotherapy. Currently, CRC has been one of the most threatening tumors affecting people's health worldwide. The excision repair cross-complementation group 1 (ERCC1) is a key enzyme for nucleotide excision repair (NER). Emerging epidemiological studies have indicated that the presence of colorectal cancer (CRC) may be relevant to the ERCC1 rs11615 genetic polymorphism. However, the results of ERCC1 rs11615 on CRC in these studies are controversial. We searched PubMed, Web of Science, Embase, CNKI, and CBM databases for the effects of ERCC1 rs11615 variant on CRC development. There was no meta-analysis focused on the diagnosis of colorectal cancer with ERCC1 rs11615 variant. We creatively carried out a meta-analysis of nine case-control studies and used Stata (version 12.0) software to integrate the pooled odds ratios (ORs) corresponding to a 95% confidence interval (CI) of overall and subgroup analysis. Our results suggest that a significant correlation was observed between rs11615 and the susceptibility of CRC OR 95% CI = 1.13 (1.04-1.23) under an allele genetic model and OR 95% CI = 1.14 (1.01-1.30) under a dominant genetic model for overall CRC. Significant statistical difference was also noted in Asians rather than Caucasians based on the ethnicity subgroups. These results suggested that there is a certain association between rs11615 and the susceptibility of colorectal cancer in the Asian populations.

Understanding via Exploration: Discovery of Interpretable Features With Deep Reinforcement Learning.

Understanding the environments through interactions has been one of the most important human intellectual activities in mastering unknown systems. Deep reinforcement learning (DRL) has already been known to achieve effective control through human-like exploration and exploitation in many applications. However, the opaque nature of deep neural network (DNN) often hides critical information about feature relevance to control, which is essential for understanding the target systems. In this article, a novel online feature selection framework, namely, the dual-world-based attentive feature selection (D-AFS), is first proposed to identify the contribution of the inputs over the whole control process. Rather than the one world used in most DRL, D-AFS has both the real world and its virtual peer with twisted features. The newly introduced attention-based evaluation (AR) module performs the dynamic mapping from the real world to the virtual world. The existing DRL algorithms, with slight modification, can learn in the dual world. By analyzing the DRL's response in the two worlds, D-AFS can quantitatively identify respective features' importance toward control. A set of experiments is performed on four classical control systems in OpenAI Gym. Results show that D-AFS can generate the same or even better feature combinations than the solutions provided by human experts and seven recent feature selection baselines. In all cases, the selected feature representations are closely correlated with the ones used by underlying system dynamic models.

Therapeutic effect of (5R)-5-hydroxytriptolide (LLDT-8) in SIV infected rhesus monkeys.

BACKGROUNDS: Human immunodeficiency virus (HIV) infections induce robust, generalized inflammatory responses and lead to pathological systemic immune activation. This abnormal immune status persists despite successful antiretroviral therapy (ART). Immune modulating strategies in conjunction with ART were tried to reduce abnormal immune activation. Previously, we demonstrated that Tripterygium Wilfordii Hook F has been shown immunosuppressive activity in HIV patients. (5R)-5-hydroxytriptolide (LLDT-8), a new analog of triptolide, and the most active ingredient of Tripterygium Wilfordii Hook F, has been shown to have lower cytotoxicity. However, the role of LLDT-8 in HIV or simian immunodeficiency virus (SIV) needs to be explored. METHODS: Six male adult Chinese rhesus monkeys were enrolled in our study. All of them were healthy and negative for SIV, and chronically SIVmac239 infected macaques were treated with LLDT-8 combined with ART (n = 4) or ART only (n = 2) after 14 weeks of infection. ART was determined at week 33, and LLDT-8 was continued until week 48. T cell immune activation and inflammation were compared during the period, and viral rebound time and reservoir were supervised after stopping ART. RESULTS: The RNA level of the two groups continued to decline after initiating ART, RNA of 4 rhesus monkeys declined to the lower limit of detection at week 20. LLDT-8 administration combined with ART did not affect T cell activation and plasma levels of IL-6 and CRP. The viral load of all the macaques in both groups was rebounded 2 weeks after ART discontinuation. Furthermore, no significant decrease of SIV DNA was observed in the LLDT-8 treatment group. CONCLUSIONS: LLDT-8 administration during chronic SIV infection had no effect on T cell activation and plasma levels; Furthermore, LLDT-8 may not contribute to suppression of viral rebound and reservoir. These results suggest that LLDT-8 is unlikely to reduce immune activation and viral persistence without additional interventions.

Combined multi-omics and network pharmacology approach reveals the role of Tripterygium Wilfordii Hook F in treating HIV immunological non-responders.

BACKGROUND: The HIV-1 infected immunological non-responders (INRs) are characterized by poor immune reconstitution after long-term treatment. Tripterygium Wilfordii Hook F (TwHF) pill is a traditional Chinese patent drug with extensive immunosuppressive effects and has been clinically proven efficacy in treating INRs. PURPOSE: The therapeutic mechanism of TwHF pills in the treatment of INRs was investigated by the combined multi-omics analysis on clinical samples and network pharmacology approach. METHODS: Clinically, the peripheral blood mononuclear cells (PBMC) samples of TwHF-treated INRs from different time points were collected to conduct the transcriptomic and proteomic profiling. Key effector pathways of TwHF were enriched and analyzed by the ingenuity pathway analysis (IPA). Computationally, the TwHF-related compounds were obtained from traditional Chinese medicine databases, and literature search and structural prediction were performed to identify TwHF-related targets. Integrated with the INR-related targets, the 'TwHF-compounds-targets-INR' network was constructed to analyze core effector targets by centrality measurement. Experimentally, the effects of TwHF compounds on the T cells activation and expression of identified targets were evaluated with in vitro cell culture. RESULTS: 33 INRs were included and treated with TwHF pills for 17 (IQR, 12-24) months. These patients experienced rapid growth in the CD4+ T cell counts and decreased T cell activation. The multi-omics analysis showed that the interferon (IFN)-signaling pathway was significantly inhibited after taking TwHF pills. The network pharmacology predicted the central role of the signal transducer and activator of transcription 1 (STAT1) in the 'TwHF-compounds-targets-INR' network. Further bioinformatic analysis predicted STAT1 would regulate over 58.8% of identified down-regulated genes. Cell experiments validated that triptolide (TPL) would serve as the major bioactivity compound of TwHF pills to inhibit the immune cell activation, the production of IFN-γ, the expression of downstream IFN-stimulated genes, and the phosphorylation of STAT1. CONCLUSION: Our research is the first to systemic verify the mechanisms of TwHF in treating INRs. The IFN signaling pathway and the STAT1 would be the major effector targets of TwHF pills in treating INRs. The TPL would be the major bioactive compound to inhibit the IFN response and the phosphorylation of STAT1. Our observations suggest the basis for further application of TPL analogous in treating INRs.

Comparison of Renal Function Biomarkers of Serum Creatinine and Cystatin C in HIV-Infected People on Dolutegravir-Containing Therapy.

Objectives: HIV-1-infected Chinese patients who were treated naïve with combination dolutegravir (DTG) and tenofovir disoproxil fumarate (TDF) group, DTG without TDF group, TDF without DTG, as well as patients switched to DTG-containing therapy from other drugs were included. Design: The dynamics of serum creatinine, cystatin C (CysC) level, eGFRcr and eGFRCysC at the baseline, 4 w, 12w, 24w, 36w and 48w for different group of patients were collected and evaluated. Methods: Changes in serum creatinine, levels, eGFRcr and eGFRCysC were analyzed among groups and in different time-points. Intra-group correlation coefficient and Bland-Altman plot were used to compare the results of eGFRcr and eGFRCysC. Results: Thirty-seven treated-naïve HIV-patients in combined DTG and TDF group (group 1), 23 in DTG without TDF patients (group 2) and 47 patients on TDF without DTG group (control group, group 3) along with 31 patients whose ART switch to DTG-containing regimens (group 4) were collected. Serum creatinine was significantly elevated in the group 1 and group 2 instead of group 3 from baseline to 48w. Mean decreased change of eGFR calculated by serum creatinine proved the same conclusion. However, there were no differences in serum cystatin C and eGFRCysC between baseline and at 48 weeks in DTG-containing groups. Moreover, the proportion of eGFRcr decreased over 30% was significantly higher in DTG-treatment group. Conclusion: We demonstrated the clinical benefits of CysC for assessing the glomerular filtration rate when evaluating renal function in HIV-1-infected patients treated with whether DTG combined with TDF or not.

Comparative Transcriptional Analysis Identified Characteristic Genes and Patterns in HIV-Infected Immunological Non-Responders.

Purpose: The incomplete immune reconstitution is a complex phenomenon among human immunodeficiency virus (HIV)-infected patients despite the fact that they have achieved persistent viral suppression under the combined antiretroviral therapy. This study aims to screen and verify the immunological characteristics and underlying mechanisms of immunological non-responders (INRs). Methods: The RNA-seq and the differentially expressed genes (DEGs) analysis were used to explore potential characteristics among INRs. Gene Ontology (GO) enrichment, ingenuity pathway analysis (IPA) analysis, Gene set enrichment analysis (GSEA) analysis, and the weighted gene co-expression network analysis (WGCNA) were used to explore the potential mechanism. The transcriptional meta-analysis was used to analyze the external efficiency. Results: The RNA-seq identified 316 DEGs among INRs. The interferon signaling pathway was enriched via GO and IPA analysis among DEGs. The combined GSEA and WGCNA analysis confirmed that the IFN response was more correlated with INR. Furthermore, IFI27 (IFN-α Inducible Protein 27, also known as ISG12) was chosen based on combined DEG analysis, WGCNA analysis, and the transcriptional meta-analysis conducted on other published datasets about INRs. The expression of IFI27 was significantly negatively correlated with the CD4+ T-cell counts of PLWH, and the predictive efficiency of IFI27 level in distinguishing PLWH with poor immune recovery was also with significant power (AUC = 0.848). Conclusion: The enhanced expression of IFI27 and the IFN response pathway are among the important immunological characteristics of INRs and exhibited promising efficiency as biomarkers for CD4+ T-cell recovery.

Self-Assembled Membrane-like Nanomaterials from Sequence-Defined Peptoid Block Copolymers.

Sequentially defined membrane-like nanomaterials have potential applications in biomedical and chemical fields due to their unique physical and chemical properties. However, these natural and synthetic nanomaterials have not been widely developed due to their complicated molecular sequence and structure, difficulties in synthesis etc. Here, we report a stable membrane-like nanomaterial composed of a monolayer or bilayer that was self-assembled from sequence-defined amphiphilic peptoid triblock (poly(N-aminoethyl glycine)-b-poly(N-octyl glycine)-b-poly(N-carboxyethyl glycine)) and diblock (poly(N-carboxyethyl glycine)-b-poly(N-octyl glycine) and poly(N-aminoethyl glycine)-b-poly(N-octyl glycine)) copolymers separately. A series of peptoid block copolymers were synthesized, and it was observed that long alkyl side chains and abundant hydrophobic blocks were necessary to form the membranes. The prepared membrane-like nanomaterials were fairly stable. They did not change obviously in shape and size with time, and they can survive after sonication. This study is expected to enrich the nanomaterial family, as well as polypeptoid science, and expand their applications in biomedicine and other fields.

Gut lactate-producing bacteria promote CD4 T cell recovery on Anti-retroviral therapy in HIV-infected patients.

Anti-retroviral therapy (ART) effectively suppresses viral replication in HIV-infected patients, however CD4 + cell restoration to normal value is not achieved by 15-20% of patients who are called immune non-responders. Gut microbiota composition has been shown to influence host immunity. Herein, to identify intestinal microbial agents that may influence the CD4 recovery in HIV-infected patients, we utilized a "Quasi-paired cohort" method to analyze intestinal metagenome data from immunological responders (IRs) and immunological non-responders (INRs). This method identified significant enrichment for Streptococcus sp. and related lactate-producing bacteria (LAB) in IRs. In a validation cohort, positive correlations between the abundance of these LAB and the post-ART CD4 + recovery was observed, and a prediction model based on these LAB performed well in predicting immune recovery. Finally, experiments using a germ-free mouse model of antibody-induced CD4 + cell depletion showed that supplementation with a lactate-producing commensal Streptococcus thermophilus strongly promoted CD4 recovery. In conclusion, our study identified a group of LAB that was associated with enhanced immune recovery in post-ART HIV-infected patients and promotes CD4 + cell restoration in a mouse model. These findings favour supplementation of LAB commensal as a therapeutic strategy for CD4 + cell count improvement in HIV-infected patients.

Whole blood as an alternative to peripheral blood mononuclear cell for detection of total HIV-1 DNA.

BACKGROUND: A more time saving, convenient, reproducible, and scalable method is needed to assess total HIV-1 DNA levels. METHODS: Frozen whole blood and peripheral blood mononuclear cell (PBMC) samples both 200 µl at the same point were used to detect total HIV-1 DNA. Automatic extraction of total HIV-1 DNA was used to ensure the consistency of sample extraction efficiency. The detection reagent was HIV-1 DNA quantitative detection kit and real-time quantitative PCR was utilized. RESULTS: Of the 44 included patients, 42 were male and 2 were female, with a median age of 33 years. Thirty-three cases were collected after receiving antiviral treatment, with a median duration of treatment of 3 months, and the other 11 cases were collected before antiviral treatment. The median viral load was 1.83 log10 copies/mL, the median CD4 and CD8 count were 94 and 680 cells/µL, and the median CD4/CD8 ratio was 0.18. The results of the two samples were 3.02 ± 0.39 log10 copies/106 PBMCs in PBMC samples and 3.05 ± 0.40 log10 copies/106 PBMCs in whole blood samples. The detection results of the two methods were highly correlated and consistent by using paired t test (P = 0.370), pearson correlation (r = 0.887, P < 0.0001) and intra-group correlation coefficient (ICC = 0.887, P < 0.0001) and bland-altman [4.55% points were outside the 95% limits of agreement (- 0.340 ~ 0.390)]. CONCLUSIONS: The results of the whole blood sample test for total HIV-1 DNA are consistent with those of PBMC samples. In a clinical setting it is recommended to use whole blood samples directly for the evaluation of the HIV reservoir.

High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients.

Objective: B-cell-activating factor (BAFF) has been determined to be involved in HIV-1 infection and is correlated with disease progression, while its homologous molecule, a proliferation-inducing ligand (APRIL), is less frequently reported, and its role remains unclear. We aimed to characterize the APRIL levels in subjects with different HIV-1 infection statuses and determine the relationships with disease progression and immune activation. Methods: The plasma levels of APRIL were compared among 17 long-term non-progressors (LTNPs), 17 typical progressors (TPs), 10 ART-treated patients, and 10 healthy donors (HDs). Seventeen LTNPs and a subset of TPs (n = 6) who initiated ART were assessed longitudinally. The correlations between the APRIL levels and markers of disease progression, B-cell count and specific antibody response, and markers of immune activation and functional cells were analyzed. Results: The circulating APRIL levels were significantly elevated in the LTNPs relative to the TPs, ART-treated patients, and HDs. The longitudinal investigation revealed that the APRIL levels were decreased during follow-up in the LTNPs. ART did not significantly influence the APRIL levels. The levels of plasma APRIL were negatively correlated with the plasma HIV-1 viral load and cellular HIV-1 DNA levels and positively correlated with the CD4+ T-cell count and CD4/CD8 ratio. An inverse correlation was observed between the APRIL and BAFF levels. Furthermore, the APRIL levels were negatively correlated with the frequency of activated CD8+ T cells and levels of interferon gamma-induced protein 10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1). Finally, positive correlations were observed among the APRIL levels, the frequency of CD8+CD28+ T cells, and natural killer (NK) cell count. Conclusion: The APRIL levels were elevated in the LTNPs and negatively correlated with disease progression and immune activation, suggesting likely protective activity in HIV-1 infection.

Super-dominant pathobiontic bacteria in the nasopharyngeal microbiota as causative agents of secondary bacterial infection in influenza patients.

The source of secondary lower respiratory tract bacterial infections in influenza patients is not fully understood. A case-control study was conducted during the 2017-2018 influenza epidemic period in Beijing, China. Nasopharyngeal swabs were collected from 52 virologically confirmed influenza patients and 24 healthy medical staff. The nasopharyngeal microbiota taxonomic composition was analysed using high-throughput sequencing of the 16S rRNA gene V3-V4 regions. The super-dominant pathobiontic bacterial genus (SDPG) was defined as that accounting for >50% of sequences in a nasopharyngeal swab. We attempted to isolate bacteria of this genus from both nasopharyngeal swabs and lower-respiratory tract samples and analyse their genetic similarities. We observed a significantly lower taxonomy richness in influenza cases compared with healthy controls. A SDPG was detected in 61% of severe cases but in only 24% of mild cases and 29% of healthy controls. In 10 cases, the species isolated from lower-respiratory tract infection sites were identified as belonging to the nasopharyngeal microbiota SDPG. Genetically identical strains were isolated from both nasopharyngeal swabs and lower-respiratory tract infection sites, including 23 Acinetobacter baumannii strains from six severe cases, six Klebsiella pneumoniae strains from two severe cases, five Pseudomonas aeruginosa strains from one severe and one mild case, and four Corynebacterium striatum strains from two severe cases. The SDPG in the nasopharyngeal microbiota are the likely cause of subsequent infection in influenza patients.

Association between lymphocyte subsets and cytomegalovirus infection status among patients with systemic lupus erythematosus: A pilot study.

This study aimed to determine the association between different lymphocyte subsets and cytomegalovirus (CMV) infection status in patients with systemic lupus erythematosus (SLE). We performed a retrospective study among SLE patients with CMV infection and collected patient socio-demographic and clinical characteristics, as well as their recorded circulating lymphocyte subsets. Univariate and multivariable logistic regression analyses examined the relationship between CMV infection status and lymphocyte subset counts. We included 125 hospitalized patients with SLE, consisting of 88 with documented CMV infection and 37 without any evidence of CMV or other infections. Among the 88 CMV-infected patients, 65 (73.8%) patients developed CMV disease and 23 (26.2%) presented as CMV viremia. Compared to uninfected patients (1520 ±â€Š101 cells/µL), lymphocytes remained stable among those with CMV viremia (1305 ±â€Š272 cells/µL, P = .995). However, compared to their uninfected counterparts, there was a marked decrease in lymphocytes among patients with CMV disease (680 ±â€Š513 cells/µL, P < .001). Analysis of lymphocyte subsets via flow cytometry showed that CD4+ T cell, CD8+ T cell, and natural killer cell counts were lower among those with CMV disease compared to those with CMV viremia and those without infection. Further, multivariable analysis showed that total lymphocyte (odds ratio [OR] 0.999, 95% confidence interval [CI] 0.998-1.000, P = .007) and CD4+ T cell counts (OR 0.99, 95% CI 0.992-0.998, P = .003) were negatively associated with CMV disease. Our findings support a potential inverse relationship between lymphopenia, specifically CD4+ T-cell lymphopenia, and CMV disease among hospitalized SLE patients.

Fluorometric determination of sulfadiazine by using molecularly imprinted poly(methyl methacrylate) nanobeads doped with manganese(II)-doped ZnS quantum dots.

The surface of poly(methyl methacrylate) nanospheres (PMMA-NSs) was molecularly imprinted with sulfadiazine by a surface imprinting method. Simultaneously, Mn(II)-doped ZnS quantum dots were incorporated into the imprinted PMMA-NSs. The morphology of the fluorescent nanoprobe was characterized by transmission electron microscopy which revealed good spheroidal core-shell structure and a homogeneous distribution of the QDs. Following binding of sulfadiazine, fluorescence (best measured at excitation/emission maxima of 335/592 nm) is increasingly quenched. The detection range is 5-40 µmol·L-1 of sulfadiazine, and the detection limit is 0.24 µmol·L-1. The fluorescence quenching mechanism is discussed, and a photo-induced electron transfer process is shown to account for quenching. The fluorescent probe was applied to the determination of sulfadiazine in spiked tap water with recoveries and RSDs of 96.6-100.2% and 2.7-3.9%, respectively. The detection of sulfadiazine in spiked lake water exhibited the recoveries and RSDs with 99.3-104.8% and 1.8-4.2%, respectively. Graphical abstract Schematic presentation of synthesis of PMMA-Ns, Mn-doped ZnS QDs, MQPs, and the elution diagram of SD from MQPs, and the relative reagents including: sodium dodecyl benzene sulfonate(SDBS), (3-aminopropyl)triethoxysilane(APTES), 3-mercaptopropionic acid (MPA), tetraethylorthosilicate(TEOS)and sulfadiazine(SD), and nanoparticles including: polymer(methyl methacrylate) nanospheres(PMMANs), MIPs@QDs@PMMANs(MQPs) and carbon quantum dots(CQDs).

The effects of antiretroviral therapy initiation time on HIV reservoir size in Chinese chronically HIV infected patients: a prospective, multi-site cohort study.

BACKGROUND: The effect of ART initiation time on HIV-1 DNA reservoir in chronically infected individuals is not well understood. Determining the potential influencing factors associated with a low HIV-1 DNA level in chronic infection is an important step toward drug-free control. METHODS: A prospective study included 444 chronically HIV-infected adults was performed. Participants were divided into two groups: early initiation group (EIG) or delayed initiation group (DIG) based on their baseline CD4 count; 350 to 500 and < 350 cells/mm3, respectively. Total HIV-1 DNA was measured by quantitative PCR. Using the Mann-Whitney U test, the HIV-1 DNA level at week 48 was compared between the two groups. The influencing factors of the HIV-1 DNA and factors associated with achieving a low HIV-1 level at week 48 were analyzed. RESULTS: The HIV-1 DNA at week 48 in EIG was significantly lower than in DIG [2.12 (1.80-2.51) vs 2.58 (2.21-2.87) log10 copies/106peripheral blood mononuclear cells (PBMCs); p = 0.001]. Early ART initiation was positively associated with lower HIV-1 DNA at week 48 (p = 0.025). Similarly, baseline HIV-1DNA (p = 0.001) was positively associated with HIV-1DNA at week 48 and baseline CD4/CD8 ratio (p = 0.001) was inversely associated with HIV-1DNA at week 48. Early ART initiation (p = 0.003) and baseline HIV-1 DNA level (p < 0.001) were positively associated with achieving HIV-1 DNA < 100 copies/106 PBMCs at week 48. CONCLUSION: Early ART initiation is positively associated with a smaller size of viral reservoir and a higher possibility of achieving a low HIV-1DNA level at week 48 in Chinese chronically HIV-1 infected adult. TRIAL REGISTRATION: NCT01844297 ; Registered 1 May, 2013.

Association Between Gut Microbiota and CD4 Recovery in HIV-1 Infected Patients.

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4+ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4+ T-cell counts of ≥350 cells/mm3 and <350 cells/mm3 after 2 years of ART, respectively. Each subject's gut microbiota composition was analyzed by metagenomics sequencing. Levels of CD4+ T cells, CD8+HLA-DR+ T cells and CD8+CD38+ T cells were measured by flow cytometry. We identified more Prevotella and fewer Bacteroides in HIV-infected individuals than in HC. Patients in INR group were enriched with Faecalibacterium prausnitzii, unclassified Subdoligranulum sp. and Coprococcus comes when compared with those in IR group. F. prausnitzii and unclassified Subdoligranulum sp. were overrepresented in individuals in VU group with CD4+ T-cell counts <350 cells/mm3. Moreover, we found that the relative abundance of unclassified Subdoligranulum sp. and C. comes were positively correlated with CD8+HLA-DR+ T-cell count and CD8+HLA-DR+/CD8+ percentage. Our study has shown that gut microbiota changes were associated with CD4+ T-cell counts and immune activation in HIV-infected subjects. Interventions to reverse gut dysbiosis and inhibit immune activation could be a new strategy for improving immune reconstitution of HIV-1-infected individuals.

The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases.The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients.We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected.There were 28 adult onset CAEBV patients. The median age was 45 (range, 20-81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever.Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell.

A higher CD4/CD8 ratio correlates with an ultralow cell-associated HIV-1 DNA level in chronically infected patients on antiretroviral therapy: a case control study.

BACKGROUND: The HIV-1 DNA reservoir is an important marker that reflects viro-immunological status and can be affected by multiple viral or cellular factors. Determining the potential factors associated with the size of the HIV-1 DNA reservoir benefits the surveillance of disease progression and antiretroviral treatments. METHODS: We conducted a case control study to explore the factors that may affect the level of HIV-1 DNA. The level of HIV-1 total DNA in peripheral blood at 5 time points was quantified by quantitative PCR. Chronically HIV-1-infected patients whose cell-associated HIV-1 DNA levels were below the detection limit after receiving antiretroviral therapy (ART) for 96 weeks were identified (group 1), and patients who still had detectable levels of cell-associated HIV-1 DNA after ATR treatment were used as the control (group 2). RESULTS: Twenty-one patients with ultralow levels of cell-associated HIV-1 DNA [<20 copies/106 peripheral blood mononuclear cells (PBMCs)] presented with a lower CD8+ T-cell count (average: 511 ± 191 versus 715 ± 256 cells/µL, p = 0.013) and a higher CD4/CD8 ratio (average: 1.04 ± 0.37 versus 0.72 ± 0.32, respectively, p = 0.002) at week 96. In the multivariate analysis, patients with a higher CD4/CD8 ratio at week 96 were more likely to have levels of HIV-1 DNA below the detection limit (per 0.1 increase, OR = 1.29, 95% CI, 1.05-1.59, p = 0.017). CONCLUSION: After matching baseline HIV-1 DNA levels, a higher CD4/CD8 ratio at week 96 was the only factor associated with an ultralow level of HIV-1 DNA. The CD4/CD8 ratio can be used as an easy biomarker to help monitor patients on ART who will be selected to participate in eradication studies.