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1.
Gene ; 722: 144127, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525397

RESUMO

Complement factor H (CFH) serves as a major down-regulator in the complement system, often utilized by bacterial pathogens to evade complement attack. Yet, little is currently known about the genetic correlation of CFH polymorphisms with sepsis due to various microbial infections. A case-control method (488 septic patients and 527 healthy individuals) was carried out in this study to investigate the genetic relationship between CFH polymorphisms (rs3753394 C/T, rs1065489 G/T and rs1061170 C/T) and susceptibility to sepsis caused by bacterial infections in Chinese Han populations. Our findings indicated that the frequency of rs3753394 CT/TT genotype in the septic patients with P. aeruginosa was significantly higher than that in the control individuals (P = 0.033, OR = 2.668, 95%CI = 1.072-6.334). The rs3753394 T allele frequency in the P. aeruginosa-infected patients was significantly increased, compared to that in the healthy controls (P = 0.014, OR = 1.68, 95%CI = 1.118-2.538). Moreover, these significant differences of rs3753394 genotype and allele frequencies remained after multiple testing corrections [P (corr.) = 0.033 for genotype; P (corr.) = 0.033 for allele]. The current study highlighted the significance of CFH polymorphism rs3753394 as a potential biomarker for targeting P. aeruginosa infection in critically ill patients.


Assuntos
Predisposição Genética para Doença , Infecções por Pseudomonas/genética , Pseudomonas aeruginosa , Sepse/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/etnologia , Fator H do Complemento/genética , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/etnologia , Sepse/diagnóstico , Sepse/etnologia , Sepse/microbiologia
3.
Virol Sin ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828587

RESUMO

HIV-1 Rev is an accessory protein that plays a key role in nuclear exportation, stabilization, and translation of the viral mRNAs. Rev of HIV-1 clade BC often shows a truncation of 16 AAs due to a premature stop codon at residue 101. This stop codon presents the highest frequency in clade BC and the lowest frequency in clade B. In order to discover the potential biological effect of this truncation on Rev activity and virus replication of clade BC, we constructed Rev expression vectors of clade BC with or without 16 AAs within C-terminal separately, and replaced the stop codon by Q in a CRF07_BC infectious clone. We found that 16 AAs truncation had no effect on expression and activity of Rev in clade BC. Also, the mutation from the stop codon to Q had no effect on virus replication of clade BC. Next, to investigate the effect of this truncation on Rev activity and replication capacity of clade B, Rev expression vectors of clade B carrying or lacking 16 AAs in C-terminal were constructed respectively, and residue Q at position 101 within Rev was substituted by the stop codon in a clade B infectious clone. It was found that 16 AAs truncation significantly down-regulated Rev expression and impaired clade B Rev activity. Furthermore, a Q-to-stop codon substitution within Rev significantly reduced viral replication fitness of clade B. These results indicate that the premature stop codon at residue 101 within Rev exerts diverse impact on viral replication among different HIV-1 clades.

4.
Mediators Inflamm ; 2019: 5306541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780861

RESUMO

Background: Previous studies have demonstrated pivotal roles of disintegrin and metalloproteinase 10 (ADAM10) in the pathogenesis of sepsis. MicroRNA- (miR-) 23b has emerged as an anti-inflammatory factor that prevents multiple autoimmune diseases. However, the underlying mechanisms of miR-23b in the regulation of ADAM10 and sepsis remain uncharacterized. Methods: The expression levels of ADAM10 and miR-23b were detected by quantitative RT-PCR and western blot analysis. Cytokine production and THP-1 cell apoptosis were measured by enzyme-linked immunosorbent and annexin V apoptosis assays. Bioinformatics analyses and qRT-PCR, western blot, and luciferase reporter assays were performed to identify ADAM10 as the target gene of miR-23b. Results: miR-23b expression was downregulated in the peripheral blood mononuclear cells of sepsis patients and LPS-induced THP-1 cells and was negatively correlated with the expression of ADAM10 and inflammatory cytokines. miR-23b regulated ADAM10 expression by directly binding to the 3'-UTR of ADAM10 mRNA. The overexpression of miR-23b alleviated the LPS-stimulated production of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and apoptosis by targeting ADAM10 in THP-1 cells. The inhibitor or knockdown of ADAM10 elicited effects similar to those of miR-23b on THP-1 cells upon LPS stimulation. Conclusions: The present study demonstrated that miR-23b negatively regulated LPS-induced inflammatory responses by targeting ADAM10. The molecular regulatory mechanism of miR-23b in ADAM10 expression and sepsis-induced inflammatory consequences may provide potential therapeutic targets for sepsis.

5.
Curr HIV Res ; 17(6): 441-451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778107

RESUMO

BACKGROUND: Pretreatment drug resistance (PDR) poses an increasing threat to the success of antiretroviral treatment (ART) programs in China. We aimed to conduct a survey of PDR among HIV patients in an area in Southwest China with extensive drug trafficking. METHODS: Consecutive cross-sectional surveys were conducted in Liangshan Prefecture of Sichuan Province from 2009 to 2018 based on the WHO-recommended method. PDR was identified by testing pol region sequences with the Stanford HIVdb algorithm (version 7.0). PDR prevalence and related factors were assessed by multivariable logistic regression. The transmission of HIV drug resistance was analyzed using a genetic transmission network. RESULTS: HIV-1 pol genes from 1889 patients were successfully amplified. The distribution of HIV- 1 genotypes was as follows: CRF07_BC (94.0%), CRF08_BC (2.3%), CRF01_AE (2.0%) and others (1.4%). Of the participants, 6.9% (95% CI: 4.1-8.1%) had pretreatment resistance to 12 antiretroviral drugs recommended by the WHO, and nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) resistance were identified among 1.4% (95% CI: 0.7-3.4%), 5.8% (95% CI: 1.2-8.7%) and 0.4% (95% CI: 0.1- 3.0%) of the patients, respectively. In the multivariate logistic model, the prevalence of PDR was 1.52-fold higher among intravenous drug users (IDUs) than among patients infected by heterosexual transmission (95% CI: 1.07-2.38; P=0.049), and the prevalence of PDR among patients diagnosed from 2017-2018 was 2.03-fold higher than that among patients diagnosed from 2009-2016 (95% CI: 1.18-5.76; P=0.018). A total of 26 clusters containing PDR and a rapidly growing drug resistancerelated cluster containing the E138Q and V179D mutations were identified by genetic transmission network analysis. CONCLUSION: The results show a moderate overall level of PDR prevalence and rapidly growing drug resistance over time. Preventive intervention should be focused on controlling the HIV epidemic among drug users, and surveillance is urgently needed to monitor the trend of PDR.

6.
AIDS Res Hum Retroviruses ; 35(11-12): 1095-1102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544479

RESUMO

Older people living with HIV (PLWH) may have delayed diagnosis and access to care and therefore have poorer disease outcomes. Little is known about HIV care and disease outcomes among older PLWH in China. This retrospective cohort study used data from all adult HIV/AIDS cases during 1988-2017 in Chongqing, China from two national databases. We compared demographic and behavioral profiles, HIV care, virologic suppression, and mortality between two age groups of 18-49 and ≥50 years. Multivariate logistic and cox regression analyses were used to calculate adjusted odds ratio (AOR) and adjusted hazard ratio (AHR) among older versus younger PLWH. Of 46,580 adult HIV/AIDS cases, 76.1% were men and 38.2% were 50 years of age or older. The proportion of older cases in men increased from 2.4% in 2002 to 51.8% in 2017, and in women from 3.3% to 57.9%. Older PLWH had a lower CD4 count than their younger counterparts at HIV diagnosis (median 323 vs. 391 cells/µL; p < .001). The average time from HIV diagnosis to initiation of antiretroviral therapy (ART) were 6.3 months among older and 12.8 months among younger PLWH (p < .001). Nearly one tenth (9.6%) had virologic failure within 12 months of ART initiation, and the odds of virologic failure among older PLWH was 80% higher [AOR 1.8; 95% confidence interval (CI), 1.1-3.0] than among younger ones after controlling for calendar year of initiating ART and other covariates. The mortality rate within 12 months of initiating ART was 9.8 deaths per 100 person years, and the risk of mortality among older PLWH was three times among younger ones (AHR, 3.1; 95% CI, 2.1-4.6). Older people represented an increasing proportion of new HIV/AIDS cases and were more likely to have virologic failure and mortality within 12 months of ART initiation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31482718

RESUMO

We reported a novel HIV-1 circulating recombinant form (CRF) among three epidemiologically unlinked patients through men having sex with men in Hebei Province, China. It was named CRF103_01B (this is temporary as we have not received the CRF number from HIV databases). A near full-length genome phylogenetic tree showed that CRF103_01B was generated by three B (Western origin) segments and CRF01_AE that was described as cluster 5 lineage of CRF01_AE (CRF01-5). The emergence of CRF103_01B increased the complexity of the HIV-1 epidemic in China.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31482723

RESUMO

In this study, we report a novel HIV-1 second-generation recombinant form composed of CRF01_AE and subtype B detected from a married HIV-positive male subject infected through homosexual behavior in Tianjin in northern China. The near full-length genome analyses showed that two regions of subtype B inserted into the CRF01_AE backbone with four recombinant breakpoints observed in the pol gene region. Subregion tree analyses demonstrated that the CRF01_AE regions of the recombinant were greatly clustered with the CRF01_AE subcluster 4 lineage, which was found primarily among men who have sex with men (MSM) in northern China. To the best of our knowledge, this is the first detection of a novel HIV-1 second-generation recombinant form (CRF01AE/B) in Tianjin, which indicates active transmission networks of HIV-1 infection among MSM in this region. The emergence of the novel second-generation recombinant form highlights the increasing complexity of HIV-1 epidemic among MSM population and the importance to monitor potential novel circulating recombinant forms.

9.
mBio ; 10(4)2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387910

RESUMO

Increasing evidence has indicated that single nucleotide polymorphisms (SNPs) are related to the susceptibility of sepsis and might provide potential evidence for the mechanisms of sepsis. Our recent preliminary study showed that the ADAM10 genetic polymorphism was clinically associated with the development of sepsis, and little is known about the underlying mechanism. The aim of this study was to confirm the association between the ADAM10 promoter rs653765 G→A polymorphism and the progression of sepsis and to discover the underlying mechanism. Clinical data showed that the rs653765 G→A polymorphism was positively correlated with the development of sepsis, as evidenced by a multiple-center case-control association study with a large sample size, and showed that EGR1 and ADAM10 levels were associated well with the different subtypes of sepsis patients. In vitro results demonstrated that the rs653765 G→A variants could functionally modulate ADAM10 promoter activity by altering the binding of the EGR1 transcription factor (TF) to the ADAM10 promoter, affecting the transcription and translation of the ADAM10 gene. Electrophoretic mobility shift assay (EMSA) followed by chromatin immunoprecipitation (ChIP) assay indicated the direct interaction. Functional studies further identified that the EGR1/ADAM10 pathway is important for the inflammatory response. EGR1 intervention in vivo decreased host proinflammatory cytokine secretion and rescued the survival and tissue injury of the mouse endotoxemia model.IMPORTANCE Sepsis is characterized as life-threatening organ dysfunction, with unacceptably high mortality. Evidence has indicated that functional SNPs within inflammatory genes are associated with susceptibility, progression, and prognosis of sepsis. These mechanisms on which these susceptible sites depended often suggest the key pathogenesis and potential targets in sepsis. In the present study, we confirmed that a functional variant acts as an important genetic factor that confers the progression of sepsis in a large sample size and in multiple centers and revealed that the variants modulate the EGR1/ADAM10 pathway and influence the severity of sepsis. We believe that we provide an important insight into this new pathway involving the regulation of inflammatory process of sepsis based on the clinical genetic evidence, which will enhance the understanding of nosogenesis of sepsis and provide the potential target for inflammation-related diseases.

10.
Curr HIV Res ; 17(2): 85-93, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269884

RESUMO

The aim of this review is to describe long-term HIV epidemiology and prevention trends in Guangxi, a provincial-level region located along a major drug trafficking corridor in southwestern China. Between 1996 and 2006, HIV transmission in Guangxi was primarily fueled by Injection Drug Use (IDU). Since 2006, heterosexual sex has become the dominant mode of HIV transmission, followed by drug injection. Moreover, older, heterosexual adults appear to be at increased risk for HIV. The vast majority of new HIV cases are attributed to local HIV subtypes already circulating within Guangxi (93%), though imported subtypes are associated with younger age groups. Since 2011, HIV incidence in Guangxi has stabilized, due in part to HIV prevention efforts that include expanded HIV testing, antiretroviral treatment, and other intervention measures. Between 1996 and 2017, Guangxi, China experienced dramatic changes in the primary HIV transmission mode and at-risk age group. Due in part to local and National AIDS control and prevention campaigns, HIV incidence trends in Guangxi no longer appear to be increasing.

11.
AIDS Res Hum Retroviruses ; 35(9): 865-869, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154808

RESUMO

Surprisingly, more new unique recombinant forms (URFs) of CRF01_AE/CRF07_BC recombinant viruses were found in Tianjin, China, recently. Here we identified another novel HIV-1 recombinant virus (TJ20170315) isolated from an HIV-1 positive man who has sex with men in Tianjin, China. Phylogenetic analysis of the near full-length genome of TJ20170315 showed that it formed a monophyletic branch within the cluster of CRF01_AE reference sequences. Recombinant analysis showed that the virus kept the CRF01_AE parental backbone, and one CRF07_BC segment was inserted into gag, pol genes of the CRF01_AE backbone. Nowadays, multiple kinds of circulating recombinant forms (CRFs) and URFs were identified among men who has sex with men in China. The emergency of URFs highlights the complexity of HIV-1 infection in Tianjin, China, and implies that the next new CRF and HIV-1 epidemic are coming on the road.

12.
Front Microbiol ; 10: 1096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178836

RESUMO

Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen. Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient. In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor. Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database). Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database. A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies. The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites. Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies. For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.

13.
AIDS Res Hum Retroviruses ; 35(8): 780-784, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31187637

RESUMO

We report in this study a novel HIV-1 second-generation recombinant form (TJIH0172) composed of CRF01_AE and CRF07_BC isolated from a married HIV-positive male subject infected through homosexual behavior in Tianjin, China. The phylogenetic analysis of the near full-length genome of TJIH0172 reveals that one region of CRF07_BC inserted into the CRF01_AE backbone with two recombinant breakpoints observed in the vpu and env gene regions, respectively. The CRF01_AE regions (the regions I and III) of the recombinant are greatly clustered with the CRF01_AE subcluster 4 lineage, which is mainly circulating among men who have sex with men (MSM) in northern China. The CRF07_BC region (II) is clustered with two sequences (JX960600 and KF250366), which were discovered in the MSM population in Liaoning Province and Beijing city in northern China, respectively. The emergence of the novel recombinant strain from a married man who has sex with men in Tianjin, China, highlights the increasing complexity of the HIV-1 epidemic between MSM and their female partners and further molecular epidemiological investigation should be taken to track married MSM and their female partners to prevent HIV transmit from HIV high-risk populations to general populations.

14.
AIDS Res Hum Retroviruses ; 35(10): 972-977, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31187643

RESUMO

We report here a novel HIV-1 recombinant form (18GXD4705) composed of CRF01_AE and subtype B, acquired from an unmarried HIV-positive young man subject infected through homosexual contact in Guangxi Province of eastern China. The phylogenetic analysis of the near full-length genome of 18GXD4705 indicated that one subtype B segment was inserted into the CRF01_AE backbone, with one recombinant breakpoint demonstrated in the pol region. The CRF01_AE region (I and III) of recombinant correlated with a previously reported subcluster 4 lineage. The B subregions (II) are greatly clustered together, with B strain references. The continued generation of this novel recombinant increases the genetic complexity and diversity of the HIV epidemic in Guangxi. In addition, further molecular epidemiological investigations should be conducted to continuously monitor the dynamic transmission of HIV-1 in the region.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31212664

RESUMO

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.

16.
Nat Commun ; 10(1): 2257, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113957

RESUMO

A major barrier to human immunodeficiency virus (HIV) cure is the existence of viral reservoirs that lead to viral rebound following discontinuation of antiretroviral therapy (ART). We postulate that enhancing cytotoxic T lymphocytes (CTL) targeting conserved envelope (Env) regions can eliminate HIV infected cells in latency. Here, we evaluate the use of adoptively transferred HIV vaccine-induced subtype C Env-specific CTLs in a macaque subtype B simian-human immunodeficiency virus (SHIV) model to determine whether plasma viremia can be controlled after ART interruption. We demonstrate that adoptive cellular therapy (ACT) using autologous Env-specific T cells augmented by therapeutic vaccination can suppress ART-free viral rebound in the SHIV model. Furthermore, phenotypic and functional characterization of adoptively transferred cells in ACT-responsive and nonresponsive animals support a critical role for cross-reactive central memory T cells in viremia control. Our study offers an approach to potentiate immunological suppression of HIV in the absence of antiviral drugs.

17.
Nat Plants ; 5(4): 414-423, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30936437

RESUMO

Lateral root (LR) emergence is a highly coordinated process involving precise cell-cell communication. Here, we show that MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6, and their upstream MAP-kinase kinases (MAPKKs), MKK4 and MKK5, function downstream of HAESA (HAE)/HAESA-LIKE2 (HSL2) and their ligand INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) during LR emergence. Loss of function of MKK4/MKK5 or MPK3/MPK6 results in restricted passage of the growing lateral root primordia (LRP) through the overlaying endodermal, cortical and epidermal cell layers, leading to reduced LR density. The MKK4/MKK5-MPK3/MPK6 module regulates the expression of cell wall remodelling genes in cells overlaying LRP and therefore controls pectin degradation in the middle lamella. Expression of constitutively active MKK4 or MKK5 driven by the HAE or HSL2 promoter fully rescues the LR emergence defect in the ida and hae hsl2 mutants. In addition, the MKK4/MKK5-MPK3/MPK6 module is indispensable in auxin-facilitated LR emergence. Our study provides insights into the auxin-governed and IDA-HAE/HLS2 ligand-receptor pair-mediated LR emergence process.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Sistema de Sinalização das MAP Quinases , Raízes de Plantas/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Raízes de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia
18.
BMJ Open ; 9(3): e025666, 2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30928945

RESUMO

OBJECTIVES: China has continued to expand antiretroviral therapy (ART) services and optimise ART guidelines in an effort to significantly reduce and prevent mortality and transmission rates among HIV patients. However, no study to date has compared treatment outcomes of initial differential antiretroviral regimens among HIV patients in a real-world setting in China. This study aimed to compare the effects of different ART regimens on treatment outcomes among adults. DESIGN: Observational retrospective cohort study. SETTING: Data from 2011 to 2013 in Guangxi, China. PARTICIPANTS: Patients aged ≥18 years (n=25 732) were selected. RESULTS: A total of 25 732 patients were included in this study. The average mortality and attrition rate were 2.64 and 4.98, respectively, per 100 person-years. Using Cox proportional hazard models, zidovudine-based (AZT-based) regimen versus stavudine-based (D4T-based) regimen had an adjusted HR (AHR) for death of 0.65 (95% CI 0.58 to 0.73); the AHR of tenofovir-based (TDF-based) versus D4T-based regimens was 0.81 (95% CI 0.71 to 0.92), and of lopinavir-ritonavir-based (LPV/r-based) versus D4T-based regimens, 1.19 (95% CI 1.04 to 1.37). AZT-based versus D4T-based regimens had an AHR for dropout of 0.89 (95% CI 0.81 to 0.97); this ratio for TDF-based versus D4T-based regimens was 0.88 (95% CI 0.80 to 0.98), and for LPV/r-based versus D4T-based regimens, 1.42 (95% CI 1.27 to 1.58). AZT-based and TDF-based regimens had a lower risk compared with D4T-based regimens, while LPV/r-based regimens had a higher risk. High gastrointestinal reactions and poor adherence were observed among HIV patients whose initial ART regimen was LPV/r-based. CONCLUSIONS: Our study found that the treatment outcomes of initial ART regimens that were AZT-based or TDF-based were significantly better than D4T-based or LPV/r-based regimens. This finding could be related to the higher rates of gastrointestinal reactions and poorer adherence associated with the LPV/r-based regimens compared with other initial ART regimens.

19.
Sex Transm Dis ; 46(4): 234-239, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30870324

RESUMO

BACKGROUND: Increasing risk of human immunodeficiency virus (HIV) heterosexual transmission can raise the potential for a more diffuse and generalized epidemic. In response to the paucity of data on HIV incidence among heterosexuals in China, we conducted a large-scale, population-based cohort study located in rural southwest China. METHODS: Baseline enrollment for the study was conducted from 2013 to 2014 and follow-up at 12 months was from 2014 to 2015 among adults 20 years or older in 3 rural counties of Southwest China. Study participants were informed of the study by brochures and leaflets distributed in outreach activities. Interviews and blood collection were conducted in private rooms. Blood samples were tested for HIV infection. RESULTS: The HIV prevalence of the sample was 0.29% (95% confidence interval [CI], 0.27-0.30) (2063 of 722,795) among the total adult population of 1,090,296 potential participants 20 years or older at baseline. Of the 720,732 individuals who tested HIV-negative at baseline, 493,990 (69%) completed the follow-up. Overall HIV incidence was 2.73 (95% CI, 2.38-3.08) per 10,000 person-years (PY) (235 of 860,627 PY). Human immunodeficiency virus incidence was associated with males, older age, less than secondary schooling and not currently being married. Human immunodeficiency virus incidence was 71.28 (95% CI, 35.21-107.35) per 10,000 PY among males aged 50 to 69 years who had less than secondary schooling and were divorced or widowed. Heterosexual sex was the dominant transmission mode for HIV seroconversions (99.0%). CONCLUSIONS: Older heterosexual males were at disproportionate risk of HIV infection. Health authorities in China need to develop and implement innovative interventions suitable for the broader population of older heterosexuals.

20.
Toxicol Appl Pharmacol ; 370: 1-13, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30862457

RESUMO

To date, the connection between inorganic mercury (Hg) and social behavior remains incompletely understood. The aim of this study was to investigate the influence of maternal autoimmunity by inorganic Hg (Hg2+) exposure on social behavior of offspring. Wild-type (WT) and immunoglobulin deficient (Ig-/-) B10.S dams fertilized by male WT B10.S or SJL mice were treated with 50 µM Hg chloride (HgCl2). Non-pregnant female WT B10.S mice were used to investigate factors regulating HgCl2-induced autoimmunity to brain. HgCl2 selectively impaired social behavior in male offspring, but not female offspring from WT B10.S dams × male SJL, in that only male offspring displayed reduced time distribution with the stranger mouse, decreased sniffing to the stranger mouse and increased self-grooming. HgCl2 did not disrupt social behavior of male or female offspring from WT B10.S dams × male WT B10.S or Ig-/- B10.S dams × male SJL. The offspring from WT and Ig-/- B10.S dams × male SJL had equivalent autoimmunity to brain antigens during HgCl2 exposure, indicating that maternal, but not offspring-derived anti-brain antibodies (Ab) impaired social behavior of the offspring. Non-pregnant WT B10.S mice treated with HgCl2 had increased anti-brain Ab dependent on increase in CD4 T cell activation and IFNγ signaling to macrophages. IFNγ interaction with macrophages drove B cells and plasma cells to produce IgG. Therefore, HgCl2 selectively impaired social behavior in males with certain genetic background via maternally derived anti-brain Ab production, thus providing a novel insight into our current understanding of Hg toxicity.

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