Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detox...Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detoxication） in treating HIV/AIDS patients in the early or middle stage. Methods： Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group （36 patients） treated with ZY-4 and the control group （36 patients） treated with placebo. The treatment course was six months. The index of OD4^＋, OD8^＋ counts, body weight, clinical symptom scoring were estimated at 4 time points （0, 1, 3 and 6 month in the course）, and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group. Results： OD4^＋ count in the ZY-4 group got elevated by 7.70 4±150.96/mm^3 on average, while that in the control group lowered by 27.33 4±85.28 /mm^3 . Fifteen out of the 30 patients in the ZY-4 group had their OD4^＋ count increased, which was evidently much higher than that in the control group （8/33, P〈0. 05）, suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating OD4^＋ count. Moreover, ZY-4 showed actions in elevating OD45RA^＋ and OD8^＋ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion： ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.展开更多
OBJECTIVE: To estimate the prevalence of liver injury among patients with acquired immunodeficiency syndrome(AIDS) who received highly active antiretroviral therapy(HAART) in rural Henan Province in China, and to expl...OBJECTIVE: To estimate the prevalence of liver injury among patients with acquired immunodeficiency syndrome(AIDS) who received highly active antiretroviral therapy(HAART) in rural Henan Province in China, and to explore whether Traditional Chinese Medicine(TCM) treatment based on HAART would increase this risk.METHODS: This was a retrospective cross-sectional study. We collected medical information on patients with AIDS from two treatment databases in2014. Criteria established by the AIDS Clinical Trials Group in 1996 were used for grading liver injury,classified based on the limit of normal(ULN) for alanine transaminase and aspartate aminotransferase:grade 1(1.25-2.5 × ULN); grade 2(2.6-5 × ULN);grade 3(5.1-10 × ULN); and grade 4(> 10 × ULN).Factors associated with liver injury were evaluated using a logistic regression model.RESULTS: A total 6953 patients with AIDS(3324 male and 3629 female patients) were enrolled into this study. The prevalence of liver injury was 22.0%(18.0% grade 1, 3.1% grade 2, 0.9% grade 3). In multivariate analysis, patients aged 34-45 years were more likely to have liver injury than patients in other age groups [adjusted odds ratio(AOR), 1.39; 95%CI, 1.01-1.91)]. Other factors associated with liver injury included male sex(AOR, 1.64; 95% CI,1.46-1.85), HIV infection via blood(AOR, 1.47; 95%CI, 1.19-1.82), hepatitis B virus antibody positive(AOR, 1.07; 95% CI, 0.85-1.36), and hepatitis C virus(HCV) antibody positive(AOR, 2.76; 95% CI,2.28-3.34).CONCLUSION: The prevalence of liver injury was relatively high among HAART-experienced patients. Several factors associated with liver injury included male sex, age 35-45 years old, HIV infection through blood, and concurrent HCV infection. TCM had no relationship with liver injury in patients receiving HAART.展开更多
To evaluate the HIV pandemic in Chongqing, the pooled PCR, IgG-capture BED enzyme immunoassay （BED-CEIA）, and cohort observations were used to estimate the HIV incidences among men who have sex with men （MSM）. 617...To evaluate the HIV pandemic in Chongqing, the pooled PCR, IgG-capture BED enzyme immunoassay （BED-CEIA）, and cohort observations were used to estimate the HIV incidences among men who have sex with men （MSM）. 617 MSM subjects completed the survey at a voluntary counseling and testing （VCT） site. The observed HIV incidence was 12.5 per 100 P-Ys （95% CI = 9.1-15.7）.展开更多
Dear Editor,Recombination contributes greatly to the diversity of human immunodeficiency virus type 1（HIV-1）.A large number of recombinant strains have been found in China,particularly in Yunnan,which is considered ...Dear Editor,Recombination contributes greatly to the diversity of human immunodeficiency virus type 1（HIV-1）.A large number of recombinant strains have been found in China,particularly in Yunnan,which is considered the HIV-1 epicenter of China.Surveillance of unique recombinant forms is helpful for prediction of new circulating recombinant forms.展开更多
Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It h...Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-a by peripheral blood mononuclear cell （PBMC）; however, whether the difference of gp120 gene could affect the secretion of TNF-a and IL-113 by glial cells is unknown. The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines. Methods In this study, we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex （ADC）. Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120, pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells. Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately. Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree. Compared to the pMIG retrovirus （gp120-negative） or U87 cells, all the gp120-positive recombinant retroviruses induced more TNF-a （P 〈0.01） and IL-113 （P 〈0.01）. In addition, compared with the L/MIG retrovirus, all the three brain gp120-positive recombinant retroviruses induced less TNF-α （P 〈0.01） and IL-1β （P 〈0.01）. Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again. The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1 β, which might supply a novel idea helping understand the pathogenesis of ADC.展开更多
BACKGROUND Lipids increase the risk of sleep apnea;however,the causality between them is still inconclusive.AIM To explore the causal relationship between serum lipids and sleep apnea using two-sample Mendelian random...BACKGROUND Lipids increase the risk of sleep apnea;however,the causality between them is still inconclusive.AIM To explore the causal relationship between serum lipids and sleep apnea using two-sample Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphism(SNP)data related to serum lipids were obtained from the Global Lipids Genetics Consortium study,which included 188578 individuals of European ancestry.Additionally,sleep apnea-related SNP data were collected from the United Kingdom Biobank study,which comprised 463005 individuals of European ancestry.Two-sample MR analysis was performed to assess the causality between serum lipids and sleep apnea based on the above public data.RESULTS Genetically predicted low-density lipoprotein(odds ratio[OR]=0.99,95%confidence interval[CI]=0.99 to 1.00;P=0.58),high-density lipoprotein(OR=0.99,95%CI=0.99 to 1.00;P=0.91),triglyceride(OR=1.00,95%CI=0.99 to 1.00;P=0.92),and total cholesterol(OR=0.99,95%CI=0.99 to 1.00;P=0.33)were causally unrelated to sleep apnea.CONCLUSION Our MR analysis suggests that genetically predicted serum lipids are not risk factors of sleep apnea.展开更多
Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV...Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.展开更多
Chinese medicine （CM） has been used in the treatment of human immunodeficiency virus （HIV） infection and acquired immunodeficiency syndrome （AIDS） for 30 years and the demonstrated therapeutic effects of CM, suc...Chinese medicine （CM） has been used in the treatment of human immunodeficiency virus （HIV） infection and acquired immunodeficiency syndrome （AIDS） for 30 years and the demonstrated therapeutic effects of CM, such as reducing plasma HIV viral load, increasing CD4＊T cell counts, promoting immunity reconstitution, ameliorating symptoms and signs, improving the health related quality of life （HRQOL） and counteracting against the effects of anti-retroviral drugs, were summarized and reviewed in this article. The authors point out that it had been a good opportunity to use CM for the treatment of HIV infection and AIDS in the past and also there are huge challenges ahead for CM research and clinicians to discover more effective CM and its underlying mechanisms for treatment of AIDS.展开更多
Men who have sex with men （MSM） are at high risk for infection with human immunodeficiency virus type 1 （HIV-1） because of risk behaviors such as multiple partners and unprotected anal intercourse （UAI）. Approxi...Men who have sex with men （MSM） are at high risk for infection with human immunodeficiency virus type 1 （HIV-1） because of risk behaviors such as multiple partners and unprotected anal intercourse （UAI）. Approximately 5% to 10% of all new HIV-1 infections are transmitted by male homosexual behaviors globally.1 The HIV epidemic in China is currently spreading from high risk groups to the general population.展开更多
Background Virus with nucleoside reverse transcriptase inhibitors （NRTIs） or nonnucleoside reverse transcriptase inhibitors （NNRTIs） resistant mutations show different evolution tendencies when the anti-viral ther...Background Virus with nucleoside reverse transcriptase inhibitors （NRTIs） or nonnucleoside reverse transcriptase inhibitors （NNRTIs） resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine （3TC） or nevirapine （NVP） resistant mutations. Methods 3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay. Results 3TC-resistant （M184I mutation） and NVP-resistant （Y181I mutation） virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages. Conclusions The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.展开更多
Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This ...Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This study is a part of the sexual well-being among older adults in China(SWELL)study,which is a multicenter cross-sectional study focused on sexual health among older adults aged 50 years and older.Participants were 680 OALHIV(≥50 years old)from the SWELL study conducted from June 2020 to December 2022.Data were collected through one-on-one interviews.We used logistic regression to assess the correlates of sexual activity and sexual satis-faction.Among all participants,37.1%were sexually active.Being older,male,in a steady relationship and employed were associated with being sexually active.The prevalence of sexual satisfaction was 69.8%among sexually active OALHIV.Being homosexual and reporting a better general health status were associated with sexual satisfaction.The OALHIV who have depressive symptoms were less likely to report sexual satisfaction.To support holistic healthy aging among OALHIV,it is important for healthcare providers to be educated about the importance of enquiring about sexual activity,satisfaction and problems and addressing concerns while conveying sex-positive attitudes during clinical reviews,as these are still critical aspects of their health and well-being.展开更多
Background： CD4 count is used to determine antiretroviral therapy （ART） eligibility. In China, flow cytometers are mostly located in urban areas with limited access by patients residing in remote areas. In an attem...Background： CD4 count is used to determine antiretroviral therapy （ART） eligibility. In China, flow cytometers are mostly located in urban areas with limited access by patients residing in remote areas. In an attempt to address this issue, we conducted a study to validate the performance ofAlere PIMA point-of-care CD4 analyzer. Methods： Venous and finger-prick blood specimens were collected from HIV-positive participants from two voluntary counseling and testing sites in Yunnan Province. Both venous and finger-prick blood specimens were tested with the PIMA analyzer. Venous blood specimens tested with the Becton Dickinson FACSCalibur were used as a reference. Results： Venous specimens from 396 and finger-prick specimens from 387 persons were available for analysis. CD4 counts by PIMA correlated well with those from FACSCalibur with an R2 of 0.91 for venous blood and 0.81 for finger-prick blood. Compared to FACSCalibur, the PIMA analyzer yielded lower counts with a mean bias of- 47.0 cells/μl （limit of agreement, [LOA]： -204-110 cells/μl） for venous blood and -71.0 cells/μl （LOA： -295-153 cells/μl） for finger-prick blood. For a CD4 threshold of 350 cells/μl, the positive predictive value （PPV） of PIMA was 84.2% and 75.7% and the negative predictive value （NPV） was 97.6% and 95.8% for venous and finger-prick blood, respectively. For an ART threshold of 500 cells/μl, the corresponding PPV was 90.3% and 84.0% and NPV was 94.3% and 93.4%, respectively. Conclusions： CD4 counting using venous blood with PIMA analyzers is a feasible alternative to a large flow cytometer to determine ART eligibility.展开更多
Background:The casein kinase 2-interacting protein-1(CKIP-1)is important in the development of osteoblasts and cardiomyocytes.However,the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells(MSCs)remain un...Background:The casein kinase 2-interacting protein-1(CKIP-1)is important in the development of osteoblasts and cardiomyocytes.However,the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells(MSCs)remain unclear.This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation.Methods:Bone marrow MSCs of CKIP-1 wild type(WT)and knockout(KO)mice were cultivated in vitro.Cell phenotype was analyzed by flow cytometry,colony formation was detected to study the proliferative ability.Osteogenic and adipogenic induction were performed.The osteogenic ability was explored by alizarin red staining,alkaline phosphatase(ALP)staining and ALP activity detection.Quantitative real-time polymerase chain reaction(qRT-PCR)was carried out to determine the mRNA expression levels of osteoblast marker genes.The adipogenic ability was detected by oil red O staining.Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume(BV/TV),bone surface area fraction/trabecular BV,trabecular number(Tb.N),and trabecular spacing(Tb.sp).Interleukin(IL)-1b was injected on WT mice of 2 months old and 18 months old,respectively.Difference in CKIP-1 expression was detected by RT-PCR and western blot.The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot.Results:ALP assays,alizarin red staining,and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis.Micro-computed tomography detection showed that among 18-month-old mice,CKIP-1 KO mice presented significantly higher bone mass compared withWTmice(P=0.02).No significant difference was observed in 2-month-old mice.In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice(4.3-fold increase at themRNA level,P=0.04).Finally,the expression levels of CKIP-1 in bone marrow(3.2-fold increase at themRNA level,P=0.03)and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1b.Conclusions:CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects.Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.展开更多
Introduction:A novel recombinant antigen-based capture enzyme immunoassay(RAg-CEIA)was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1(HIV-1)incidence in China.M...Introduction:A novel recombinant antigen-based capture enzyme immunoassay(RAg-CEIA)was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1(HIV-1)incidence in China.Methods:We employed orthogonal experimental design to optimize RAg-CEIA by adjusting raw material dilution ratios.The assay was used to measure normalized optical density(ODn)values in 171 longitudinal plasma specimens from 51 HIV-1 seroconverting individuals,plotted against estimated days post-seroconversion.We determined the optimal ODn threshold value for differentiating recent from long-term infections and calculated the mean duration of recent infection(MDRI)for incidence estimation.The false recent rate(FRR)was determined using 481 HIV-1 antibody-positive specimens with infection durations exceeding twice the MDRI.Results:Optimal RAg-CEIA parameters were established with a raw material dilution ratio of 1/12 for calibrator preparation and an enzyme conjugate titer of 1:1200.ODn values demonstrated consistent temporal increases across HIV-1 seroconverting individuals,though with notable kinetic heterogeneity in individual responses.The optimal ODn threshold value of 0.8 for distinguishing recent from long-term infections corresponded to an MDRI of 205 days and an FRR of 4.78%.Conclusions:The optimized RAg-CEIA effectively differentiates recent from long-term HIV-1 infections at the population level,enabling reliable HIV-1 incidence estimation in China.展开更多
Precise identification of HIV transmission among populations is a key step in public health responses.However,the HIV transmission network is usually difficult to determine.HIV molecular networks can be determined by ...Precise identification of HIV transmission among populations is a key step in public health responses.However,the HIV transmission network is usually difficult to determine.HIV molecular networks can be determined by phylogenetic approach,genetic distance-based approach,and a combination of both approaches.These approaches are increasingly used to identify transmission networks among populations,reconstruct the history of HIV spread,monitor the dynamics of HIV transmission,guide targeted intervention on key subpopulations,and assess the effects of interventions.Simulation and retrospective studies have demonstrated that these molecular network-based interventions are more cost-effective than random or traditional interventions.However,we still need to address several challenges to improve the practice of molecular network-guided targeting interventions to finally end the HIV epidemic.The data remain limited or difficult to obtain,and more automatic real-time tools are required.In addition,molecular and social networks must be combined,and technical parameters and ethnic issues warrant further studies.展开更多
Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect ...Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.展开更多
Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral the...Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral therapy.Methods:Polypeptides that covered the amino acid sequence on the interface of Vpu-tetherin complex were designed.Phenotypic susceptibilities and cellular toxicities to the polypeptides were measured.The mechanisms of the anti-HIV-1 polypeptides were determined by the Western blot analysis and laser confocal scanning.Seven 20-mer polypeptides from wild-type Vpu amino acid sequence were designed.Results:We report the design and identification of 3 novel anti-HIV-1 polypeptides that derived from Vpu se-quence which can efficiently inhibit HIV-1 infection.A pilot mechanism study showed that the active polypeptide could counteract Vpu-mediated tetherin downregulation.Laser confocal image scanning study showed that the polypeptides bound on the cell surface with a receptor specific binding manner,which may target tetherin that expressed on cell surface.Conclusion:Our work provided first evidence that counteracting Vpu-mediated tetherin downregulation could be a target for novel anti-HIV-1 drug design.Future works to provide direct evidence of inhibitors interact with teth-erin at atomic resolution and the development of small molecules inhibitors targeting Vpu-tetherin interactions may open a new avenue for novel antiretroviral therapy.展开更多
Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of ...Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of the human genome.Most integrated HERVs have lost their coding capacity and remain silent due to frame shifts,mutations,and sequence deletions or insertions over the millions of years,but their expression is highly regulated by epigenetic and host defense mechanisms.However,there are still some HERV genes that have intact open reading frames due to recent integration into the human genome or positive selective pressure.The abnormal activation of HERVs may contribute to diseases or their pathology,such as malignant tumors,autoimmune diseases,and nervous system diseases.The occurrence and development of hematological malignant tumors(HMTs)is a complex process involving interactions of multiple genetic and environmental factors.The abnormal activation of HERVs may contribute to the pathology of HMTs via indirect mechanisms.In this review,we address the discovery of endogenous retroviruses in vertebrates,and the classification and genomic structure of HERVs.Among HERV family members,HERV-K is the latest type of HERV integrated into the human genome and it has the strongest transcriptional activity.We explore the currently known expression of HERV-K proto-oncogenes in HMTs and further address potential research and therapeutic approaches.However,much remains to be learned about not only the impact of HERVs on the occurrence of HMTs,but also the potential value of HERVs as diagnostic and therapeutic targets for HMTs.展开更多
基金Supported by the Projects of Ministry of Science and Tech-nology for 10th Five-year Plan (2001BA701A18)
文摘Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detoxication） in treating HIV/AIDS patients in the early or middle stage. Methods： Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group （36 patients） treated with ZY-4 and the control group （36 patients） treated with placebo. The treatment course was six months. The index of OD4^＋, OD8^＋ counts, body weight, clinical symptom scoring were estimated at 4 time points （0, 1, 3 and 6 month in the course）, and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group. Results： OD4^＋ count in the ZY-4 group got elevated by 7.70 4±150.96/mm^3 on average, while that in the control group lowered by 27.33 4±85.28 /mm^3 . Fifteen out of the 30 patients in the ZY-4 group had their OD4^＋ count increased, which was evidently much higher than that in the control group （8/33, P〈0. 05）, suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating OD4^＋ count. Moreover, ZY-4 showed actions in elevating OD45RA^＋ and OD8^＋ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion： ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.
基金Supported by National Natural Science Foundation of China(No.81803953,81873289,81873187)China Postdoctoral Science Foundation(No.2015M582190,2017M612406)Special Scientific Research of Traditional Chinese Medicine of Henan Province in China(No.2015ZY02097,2016ZY2036,2018ZY2080)
文摘OBJECTIVE: To estimate the prevalence of liver injury among patients with acquired immunodeficiency syndrome(AIDS) who received highly active antiretroviral therapy(HAART) in rural Henan Province in China, and to explore whether Traditional Chinese Medicine(TCM) treatment based on HAART would increase this risk.METHODS: This was a retrospective cross-sectional study. We collected medical information on patients with AIDS from two treatment databases in2014. Criteria established by the AIDS Clinical Trials Group in 1996 were used for grading liver injury,classified based on the limit of normal(ULN) for alanine transaminase and aspartate aminotransferase:grade 1(1.25-2.5 × ULN); grade 2(2.6-5 × ULN);grade 3(5.1-10 × ULN); and grade 4(> 10 × ULN).Factors associated with liver injury were evaluated using a logistic regression model.RESULTS: A total 6953 patients with AIDS(3324 male and 3629 female patients) were enrolled into this study. The prevalence of liver injury was 22.0%(18.0% grade 1, 3.1% grade 2, 0.9% grade 3). In multivariate analysis, patients aged 34-45 years were more likely to have liver injury than patients in other age groups [adjusted odds ratio(AOR), 1.39; 95%CI, 1.01-1.91)]. Other factors associated with liver injury included male sex(AOR, 1.64; 95% CI,1.46-1.85), HIV infection via blood(AOR, 1.47; 95%CI, 1.19-1.82), hepatitis B virus antibody positive(AOR, 1.07; 95% CI, 0.85-1.36), and hepatitis C virus(HCV) antibody positive(AOR, 2.76; 95% CI,2.28-3.34).CONCLUSION: The prevalence of liver injury was relatively high among HAART-experienced patients. Several factors associated with liver injury included male sex, age 35-45 years old, HIV infection through blood, and concurrent HCV infection. TCM had no relationship with liver injury in patients receiving HAART.
基金supported by the Department of Health and Family Counseling,Chongqing[2016HBRC009,2017ZDXM001]
文摘To evaluate the HIV pandemic in Chongqing, the pooled PCR, IgG-capture BED enzyme immunoassay （BED-CEIA）, and cohort observations were used to estimate the HIV incidences among men who have sex with men （MSM）. 617 MSM subjects completed the survey at a voluntary counseling and testing （VCT） site. The observed HIV incidence was 12.5 per 100 P-Ys （95% CI = 9.1-15.7）.
基金supported by the Applied Basic Research Programs of the Science and Technology Department of Yunnan Province(Grant No.2013FZ217)National Key S&T Special Projects on Major Infectious Diseases(Grant No.2012ZX10001-002)approved by the ethics committees of Health Department of Yunnan Province
文摘Dear Editor,Recombination contributes greatly to the diversity of human immunodeficiency virus type 1（HIV-1）.A large number of recombinant strains have been found in China,particularly in Yunnan,which is considered the HIV-1 epicenter of China.Surveillance of unique recombinant forms is helpful for prediction of new circulating recombinant forms.
文摘Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-a by peripheral blood mononuclear cell （PBMC）; however, whether the difference of gp120 gene could affect the secretion of TNF-a and IL-113 by glial cells is unknown. The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines. Methods In this study, we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex （ADC）. Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120, pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells. Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately. Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree. Compared to the pMIG retrovirus （gp120-negative） or U87 cells, all the gp120-positive recombinant retroviruses induced more TNF-a （P 〈0.01） and IL-113 （P 〈0.01）. In addition, compared with the L/MIG retrovirus, all the three brain gp120-positive recombinant retroviruses induced less TNF-α （P 〈0.01） and IL-1β （P 〈0.01）. Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again. The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1 β, which might supply a novel idea helping understand the pathogenesis of ADC.
文摘BACKGROUND Lipids increase the risk of sleep apnea;however,the causality between them is still inconclusive.AIM To explore the causal relationship between serum lipids and sleep apnea using two-sample Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphism(SNP)data related to serum lipids were obtained from the Global Lipids Genetics Consortium study,which included 188578 individuals of European ancestry.Additionally,sleep apnea-related SNP data were collected from the United Kingdom Biobank study,which comprised 463005 individuals of European ancestry.Two-sample MR analysis was performed to assess the causality between serum lipids and sleep apnea based on the above public data.RESULTS Genetically predicted low-density lipoprotein(odds ratio[OR]=0.99,95%confidence interval[CI]=0.99 to 1.00;P=0.58),high-density lipoprotein(OR=0.99,95%CI=0.99 to 1.00;P=0.91),triglyceride(OR=1.00,95%CI=0.99 to 1.00;P=0.92),and total cholesterol(OR=0.99,95%CI=0.99 to 1.00;P=0.33)were causally unrelated to sleep apnea.CONCLUSION Our MR analysis suggests that genetically predicted serum lipids are not risk factors of sleep apnea.
基金supported in part by the National Key S&T Special Projects on Major Infectious Diseases (Grant No. 2008ZX10001-002, 2008ZX10001-012)the National Natural Science Foundation of China (No. 30700706)
文摘Neutralizing antibodies are considered to be an important protective parameter used in HIV-1 vaccine evaluation. However, the exact role that neutralizing antibodies plays in controlling the disease progression of HIV-1 infected peoples is still undetermined. In this paper, we compared the protective function of the neutralizing antibody response in the plasma from LTNP and TP against clade B and clade C pseudoviruses. No difference in the neutralizing activities between the plasma from LTNP and TP was found, which was consistent with the most recent reports. In addition, no correlations between the titer or breadth and CD4+ or viral load in HIV-1 infected individuals were found. The protective roles played by neutralizing antibodies in controlling disease progression of HIV-1 infected people need to be considered in a new viewpoint.
基金The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2013 ~Supported by the National Special S＆T Program on Major Infectious Diseases （No. 2013ZX10005001-001 and No. 2012ZX10005010-001-002）, the Research Project for Practice Development of National Traditional Chinese Medicine Clinical Research Bases （No. JDZX2012023）, and the Innovation Scientists and Technicians Troop Construction Projects of Zhengzhou City （No.10CXTD140）
文摘Chinese medicine （CM） has been used in the treatment of human immunodeficiency virus （HIV） infection and acquired immunodeficiency syndrome （AIDS） for 30 years and the demonstrated therapeutic effects of CM, such as reducing plasma HIV viral load, increasing CD4＊T cell counts, promoting immunity reconstitution, ameliorating symptoms and signs, improving the health related quality of life （HRQOL） and counteracting against the effects of anti-retroviral drugs, were summarized and reviewed in this article. The authors point out that it had been a good opportunity to use CM for the treatment of HIV infection and AIDS in the past and also there are huge challenges ahead for CM research and clinicians to discover more effective CM and its underlying mechanisms for treatment of AIDS.
文摘Men who have sex with men （MSM） are at high risk for infection with human immunodeficiency virus type 1 （HIV-1） because of risk behaviors such as multiple partners and unprotected anal intercourse （UAI）. Approximately 5% to 10% of all new HIV-1 infections are transmitted by male homosexual behaviors globally.1 The HIV epidemic in China is currently spreading from high risk groups to the general population.
基金This work was supported by the National Grand Fundamental Research 973 Program of China （No. 2006CB504206） and the National Natural Science Foundation of China （No. 30830088）.
文摘Background Virus with nucleoside reverse transcriptase inhibitors （NRTIs） or nonnucleoside reverse transcriptase inhibitors （NNRTIs） resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine （3TC） or nevirapine （NVP） resistant mutations. Methods 3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay. Results 3TC-resistant （M184I mutation） and NVP-resistant （Y181I mutation） virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages. Conclusions The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.
基金supported by the Natural Science Foundation of China International/Regional Research Collaboration Project(72061137001)Natural Science Foundation of China Excellent Young Scientists Fund(82022064)+2 种基金Chongqing Talents Program for Innovative and Entrepreneurial Pioneers(cstc2021ycjh-bgzxm0097)Chongqing Natural Science Foundation Project(cstc2021jcyj-msxmX1171)Chinese State Key Laboratory of Infectious Disease Prevention and Control(2021SKLID303).
文摘Sexual lifestyles are closely related to overall human health and well-being.Few studies have focused on sexual lifestyles among older adults living with HIV(OALHIV),especially in low-and middle-income countries.This study is a part of the sexual well-being among older adults in China(SWELL)study,which is a multicenter cross-sectional study focused on sexual health among older adults aged 50 years and older.Participants were 680 OALHIV(≥50 years old)from the SWELL study conducted from June 2020 to December 2022.Data were collected through one-on-one interviews.We used logistic regression to assess the correlates of sexual activity and sexual satis-faction.Among all participants,37.1%were sexually active.Being older,male,in a steady relationship and employed were associated with being sexually active.The prevalence of sexual satisfaction was 69.8%among sexually active OALHIV.Being homosexual and reporting a better general health status were associated with sexual satisfaction.The OALHIV who have depressive symptoms were less likely to report sexual satisfaction.To support holistic healthy aging among OALHIV,it is important for healthcare providers to be educated about the importance of enquiring about sexual activity,satisfaction and problems and addressing concerns while conveying sex-positive attitudes during clinical reviews,as these are still critical aspects of their health and well-being.
文摘Background： CD4 count is used to determine antiretroviral therapy （ART） eligibility. In China, flow cytometers are mostly located in urban areas with limited access by patients residing in remote areas. In an attempt to address this issue, we conducted a study to validate the performance ofAlere PIMA point-of-care CD4 analyzer. Methods： Venous and finger-prick blood specimens were collected from HIV-positive participants from two voluntary counseling and testing sites in Yunnan Province. Both venous and finger-prick blood specimens were tested with the PIMA analyzer. Venous blood specimens tested with the Becton Dickinson FACSCalibur were used as a reference. Results： Venous specimens from 396 and finger-prick specimens from 387 persons were available for analysis. CD4 counts by PIMA correlated well with those from FACSCalibur with an R2 of 0.91 for venous blood and 0.81 for finger-prick blood. Compared to FACSCalibur, the PIMA analyzer yielded lower counts with a mean bias of- 47.0 cells/μl （limit of agreement, [LOA]： -204-110 cells/μl） for venous blood and -71.0 cells/μl （LOA： -295-153 cells/μl） for finger-prick blood. For a CD4 threshold of 350 cells/μl, the positive predictive value （PPV） of PIMA was 84.2% and 75.7% and the negative predictive value （NPV） was 97.6% and 95.8% for venous and finger-prick blood, respectively. For an ART threshold of 500 cells/μl, the corresponding PPV was 90.3% and 84.0% and NPV was 94.3% and 93.4%, respectively. Conclusions： CD4 counting using venous blood with PIMA analyzers is a feasible alternative to a large flow cytometer to determine ART eligibility.
基金Supported by the grants from the National Key Research and Development Project(No.2017YFB1304300)Conversion Fund of PLA General Hospital(No.2017tm-018)the Clinical Research Support Fund of PLA General Hospital(No.2017fc-tsys-2013).
文摘Background:The casein kinase 2-interacting protein-1(CKIP-1)is important in the development of osteoblasts and cardiomyocytes.However,the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells(MSCs)remain unclear.This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation.Methods:Bone marrow MSCs of CKIP-1 wild type(WT)and knockout(KO)mice were cultivated in vitro.Cell phenotype was analyzed by flow cytometry,colony formation was detected to study the proliferative ability.Osteogenic and adipogenic induction were performed.The osteogenic ability was explored by alizarin red staining,alkaline phosphatase(ALP)staining and ALP activity detection.Quantitative real-time polymerase chain reaction(qRT-PCR)was carried out to determine the mRNA expression levels of osteoblast marker genes.The adipogenic ability was detected by oil red O staining.Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume(BV/TV),bone surface area fraction/trabecular BV,trabecular number(Tb.N),and trabecular spacing(Tb.sp).Interleukin(IL)-1b was injected on WT mice of 2 months old and 18 months old,respectively.Difference in CKIP-1 expression was detected by RT-PCR and western blot.The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot.Results:ALP assays,alizarin red staining,and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis.Micro-computed tomography detection showed that among 18-month-old mice,CKIP-1 KO mice presented significantly higher bone mass compared withWTmice(P=0.02).No significant difference was observed in 2-month-old mice.In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice(4.3-fold increase at themRNA level,P=0.04).Finally,the expression levels of CKIP-1 in bone marrow(3.2-fold increase at themRNA level,P=0.03)and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1b.Conclusions:CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects.Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.
基金Supported by the National Science and Technology Major Project of the 13th Five-year Plan(grants 2017ZX10201101-002-003 and 2018ZX10721102-003-002)。
文摘Introduction:A novel recombinant antigen-based capture enzyme immunoassay(RAg-CEIA)was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1(HIV-1)incidence in China.Methods:We employed orthogonal experimental design to optimize RAg-CEIA by adjusting raw material dilution ratios.The assay was used to measure normalized optical density(ODn)values in 171 longitudinal plasma specimens from 51 HIV-1 seroconverting individuals,plotted against estimated days post-seroconversion.We determined the optimal ODn threshold value for differentiating recent from long-term infections and calculated the mean duration of recent infection(MDRI)for incidence estimation.The false recent rate(FRR)was determined using 481 HIV-1 antibody-positive specimens with infection durations exceeding twice the MDRI.Results:Optimal RAg-CEIA parameters were established with a raw material dilution ratio of 1/12 for calibrator preparation and an enzyme conjugate titer of 1:1200.ODn values demonstrated consistent temporal increases across HIV-1 seroconverting individuals,though with notable kinetic heterogeneity in individual responses.The optimal ODn threshold value of 0.8 for distinguishing recent from long-term infections corresponded to an MDRI of 205 days and an FRR of 4.78%.Conclusions:The optimized RAg-CEIA effectively differentiates recent from long-term HIV-1 infections at the population level,enabling reliable HIV-1 incidence estimation in China.
基金This work was supported in part by the Mega-Projects of the National Science Research for the 13th Five-Year Plan(No.2017ZX10201101),Innovation Team Development Program of the Ministry of Education(No.IRT_16R70)the National Natural Science Foundation of China(No.81871637)Central Publicinterest Scientific Institution Basal Research Fund(No.2018PT31042).
文摘Precise identification of HIV transmission among populations is a key step in public health responses.However,the HIV transmission network is usually difficult to determine.HIV molecular networks can be determined by phylogenetic approach,genetic distance-based approach,and a combination of both approaches.These approaches are increasingly used to identify transmission networks among populations,reconstruct the history of HIV spread,monitor the dynamics of HIV transmission,guide targeted intervention on key subpopulations,and assess the effects of interventions.Simulation and retrospective studies have demonstrated that these molecular network-based interventions are more cost-effective than random or traditional interventions.However,we still need to address several challenges to improve the practice of molecular network-guided targeting interventions to finally end the HIV epidemic.The data remain limited or difficult to obtain,and more automatic real-time tools are required.In addition,molecular and social networks must be combined,and technical parameters and ethnic issues warrant further studies.
文摘Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.
文摘Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral therapy.Methods:Polypeptides that covered the amino acid sequence on the interface of Vpu-tetherin complex were designed.Phenotypic susceptibilities and cellular toxicities to the polypeptides were measured.The mechanisms of the anti-HIV-1 polypeptides were determined by the Western blot analysis and laser confocal scanning.Seven 20-mer polypeptides from wild-type Vpu amino acid sequence were designed.Results:We report the design and identification of 3 novel anti-HIV-1 polypeptides that derived from Vpu se-quence which can efficiently inhibit HIV-1 infection.A pilot mechanism study showed that the active polypeptide could counteract Vpu-mediated tetherin downregulation.Laser confocal image scanning study showed that the polypeptides bound on the cell surface with a receptor specific binding manner,which may target tetherin that expressed on cell surface.Conclusion:Our work provided first evidence that counteracting Vpu-mediated tetherin downregulation could be a target for novel anti-HIV-1 drug design.Future works to provide direct evidence of inhibitors interact with teth-erin at atomic resolution and the development of small molecules inhibitors targeting Vpu-tetherin interactions may open a new avenue for novel antiretroviral therapy.
文摘Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of the human genome.Most integrated HERVs have lost their coding capacity and remain silent due to frame shifts,mutations,and sequence deletions or insertions over the millions of years,but their expression is highly regulated by epigenetic and host defense mechanisms.However,there are still some HERV genes that have intact open reading frames due to recent integration into the human genome or positive selective pressure.The abnormal activation of HERVs may contribute to diseases or their pathology,such as malignant tumors,autoimmune diseases,and nervous system diseases.The occurrence and development of hematological malignant tumors(HMTs)is a complex process involving interactions of multiple genetic and environmental factors.The abnormal activation of HERVs may contribute to the pathology of HMTs via indirect mechanisms.In this review,we address the discovery of endogenous retroviruses in vertebrates,and the classification and genomic structure of HERVs.Among HERV family members,HERV-K is the latest type of HERV integrated into the human genome and it has the strongest transcriptional activity.We explore the currently known expression of HERV-K proto-oncogenes in HMTs and further address potential research and therapeutic approaches.However,much remains to be learned about not only the impact of HERVs on the occurrence of HMTs,but also the potential value of HERVs as diagnostic and therapeutic targets for HMTs.
