Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Math Biosci Eng ; 18(5): 6961-6977, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34517566

RESUMO

This paper elucidates that the AIDS/HIV incidence rate differences exist among different population and regions, especially among the old and college students. Due to the effect of age, the AIDS incidence peak in males aged 20-35 years and 50 years old both in Chongqing and Shenzhen, and the incidence rate and increasing spread in males was higher than that of females under period effect. In the local population in Chongqing and Shenzhen, the incidence rate of males in over 40, below and in the whole age groups are predicted to increase sharply in the future six years, while in females, the incidence rates among over 40-year-old and the whole age groups were predicted to increase as well. The incidence rate among homosexually transmitted patients reaches the peak in the 20-35, the incidence rate of patients transmitted through heterosexual reaches the peak around 50-year-old. Under the effect of period, AIDS/HIV incidence rate of patients transmitted through sexual routes showed an upward trend both in Chongqing and Shenzhen. The incidence rate of patients aged between 41 and 70 years old presents with an upward trend in the future six years. The results show great differences exist in the AIDS/HIV incidence between males and females, therefore it is necessary to take specific measures respectively.


Assuntos
Infecções por HIV , Comportamento Sexual , Adulto , Idoso , China/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Heterossexualidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
2.
Retrovirology ; 18(1): 22, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399785

RESUMO

BACKGROUND: CRF55_01B is a newly identified HIV-1 circulating recombinant form originated from MSM in China. However, its impact on the disease progression and transmission risk has not been investigated. This study aimed to determine the impact of CRF55_01B infection on viral dynamics and immunological status so as to provide scientific evidence for further control and prevention effort on CRF55_01B. Linear mixed effect models were applied to evaluate CD4 cell count decline and viral load increase by subtype. RESULTS: Of the 3418 blood samples, 1446 (42.3%) were CRF07_BC, 1169 (34.2%) CRF01_AE, 467 (13.7%) CRF55_01B, 249 (7.3%) type B, and 87 (2.5%) other subtypes (CRF_08BC, CRF_01B, C). CRF55_01B had become the third predominant strain since 2012 in Shenzhen, China. CRF55_01B-infected MSM showed lower median of CD4 count than CRF07_BC-infected MSM (349.5 [IQR, 250.2-474.8] vs. 370.0 [IQR, 278.0-501.0], P < 0.05). CRF55_01B infection was associated with slower loss of CD4 count than CRF01_AE (13.6 vs. 23.3 [cells/µl]¹/²/year, P < 0.05)among MSM with initial CD4 count of 200-350 cells/µl. On the other hand, those infected with CRF55_01B showed higher median plasma HIV RNA load (5.4 [IQR, 5.0-5.9]) than both CRF01_AE (5.3 [IQR, 4.8-5.7], P < 0.05) and CRF07_BC (5.0 log10 [IQR, 4.5-5.5], P < 0.001) at the initiation of antiretroviral therapy. Furthermore, the annual increasing rate of viral load for CRF55_01B infection was significantly higher than that of CRF07_BC (2.0 vs. 0.7 log10 copies/ml/year, P < 0.01). CONCLUSIONS: The relatively lower CD4 count and faster increase of plasma HIV RNA load of CRF55_01B-infected MSM without antiretroviral therapy suggest that CRF55_01B may lead to longer asymptomatic phase and higher risk of HIV transmission. Strengthened surveillance, tailored prevention strategies and interventions, and in-depth research focusing on CRF55_01B are urgently needed to forestall potential epidemic.

4.
BMC Microbiol ; 21(1): 194, 2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174835

RESUMO

BACKGROUND: Serological test is helpful in confirming and tracking infectious diseases in large population with the advantage of fast and convenience. Using the specific epitope peptides identified from the whole antigen as the detection antigen is sensitive and relatively economical. The development of epitope peptide-based detection kits for COVID-19 patients requires comprehensive information about epitope peptides. But the data on B cell epitope of SARS-CoV-2 spike protein is still limited. More importantly, there is a lack of serological data on the peptides in the population. In this study, we aimed to identify the B cell epitope peptides of spike protein and detect the reactivity in serum samples, for further providing data support for their subsequent serological applications. RESULTS: Two B cell linear epitopes, P104 and P82, located in non-RBD region of SARS-CoV-2 S protein were identified by indirect ELISA screening of an overlapping peptide library of the S protein with COVID-19 patients' convalescent serum. And the peptides were verified by testing with 165 serum samples. P104 has not been reported previously; P82 is contained in peptide S21P2 reported before. The positive reaction rates of epitope peptides S14P5 and S21P2, the two non-RBD region epitopes identified by Poh et al., and P82 and P104 were 77.0%, 73.9%, 61.2% and 30.3%, respectively, for 165 convalescent sera, including 30 asymptomatic patients. Although P104 had the lowest positive rate for total patients (30.3%), it exhibited slight advantage for detection of asymptomatic infections (36.7%). Combination of epitopes significantly improved the positive reaction rate. Among all combination patterns, (S14P5 + S21P2 + P104) pattern exhibited the highest positive reaction rate for all patients (92.7%), as well as for asymptomatic infections (86.7%), confirming the feasibility of P104 as supplementary antigen for serological detection. In addition, we analyzed the correlation between epitopes with neutralizing antibody, but only S14P5 had a medium positive correlation with neutralizing antibody titre (rs = 0.510, P < 0.01). CONCLUSION: Our research proved that epitopes on non-RBD region are of value in serological detection especially when combination more than one epitope, thus providing serological reaction information about the four epitopes, which has valuable references for their usage.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19 , Ensaio de Imunoadsorção Enzimática/métodos , Epitopos de Linfócito B , Glicoproteína da Espícula de Coronavírus/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Criança , Pré-Escolar , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/imunologia , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
5.
J Infect ; 83(1): 76-83, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932447

RESUMO

OBJECTIVES: Shenzhen is suffering severe HIV epidemic. No systematic surveillance on high risk populations, HIV genetic diversity, transmitted drug resistance (TDR) and molecular transmission clusters (MTCs) have been reported yet. In this study, we described them based on newly diagnosed HIV positive cases from 2011 to 2018 in Shenzhen city, China. METHODS: Plasma samples of newly reported HIV positive cases in Shenzhen, China were collected from 2011 to 2018. The HIV pol gene was amplified and sequenced for subtyping, genetic characterization, TDR and phylogenetic analysis. Demographic and risk characteristics associated with transmitted drug resistance-associated mutations (TDRAMs) and MTCs were explored by using logistic regression analyses. RESULTS: 10,378 HIV pol sequences were successfully obtained from newly diagnosed patients with available background information. The most prevalent HIV-1 subtype was CRF07_BC (40.92%). CRF07_BC, CRF55_01B and URFs increased across years. Total TDR was 6.02% during 2011 to 2018. CRF01_AE, CRF08_BC, CRF55_01B and subtype B were more likely to be associated with TDRAMs than CRF07_BC. 4460 (42.98%) patients were infected with strains included in MTCs. Patients younger than 30 and over 50 years were more likely to cluster. CONCLUSIONS: The prevalence of HIV-1 drug resistance and molecular transmission clusters in Shenzhen should raise a high alert. Interventions targeting on patients with strains locating in MTCs should be considered to improve prevention effect in Shenzhen.


Assuntos
Infecções por HIV , HIV-1 , China/epidemiologia , Farmacorresistência Viral/genética , Genes pol , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Filogenia
6.
mSphere ; 6(3)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952659

RESUMO

Altered gut virome and expanded abundance of certain viruses were found in HIV-1-infected individuals. It remains largely unknown how plasma virus composition changes during HIV-1 infection and antiretroviral therapy (ART). We performed viral metagenomic analysis on viral particles enriched from human plasma from 101 men who have sex with men (MSM) with or without HIV-1 infection and whether or not on ART and compared the differences in the plasma virome. An increased plasma viral abundance of main eukaryotic viruses was observed during HIV-1 infection in MSM, especially in AIDS patients (CD4+ T cell counts of <200). Anellovirus, pegivirus and hepatitis B virus (HBV) were the most abundant blood-borne viruses detected among MSM and HIV-1-infected individuals, and anellovirus and pegivirus were closely related to HIV-1 infection. High diversity of anelloviruses was found mostly in HIV-1-infected MSM, and their abundance was positively correlated with the HIV-1 viral load, but negatively correlated with both CD4+ T cell counts and CD4+/CD8+ ratio; in contrast, the abundance of pegivirus showed opposite correlations. ART usage could restore the plasma virome toward that of HIV-1-negative individuals. These data showed an expansion in abundance of certain viruses during HIV-1 infection, indicating the higher risk of shedding some blood-borne viruses in these individuals. These investigations indicate that both anellovirus and pegivirus may play certain roles in HIV disease progression.IMPORTANCE Though an increasing number of studies have indicated the existence of an interaction between the virome and human health or disease, the specific role of these plasma viral components remains largely unsolved. We provide evidence here that an altered plasma virome profile is associated with different immune status of HIV-1 infection. Specific resident viruses, such as anellovirus and pegivirus, may directly or indirectly participate in the disease progression of HIV-1 infection. These results can help to determine their clinical relevance and design potential therapies.

7.
PLoS One ; 16(5): e0251929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34015057

RESUMO

OBJECTIVES: To analyze the trends of HIV/syphilis/HSV-2 seropositive rate and explore the related factors with HSV-2 infection to provide the basis for adjusting STD intervention strategies and formulating prevention and control measures among MSM in Shenzhen. METHODS: Time-location sampling was conducted among MSM in Shenzhen in 2012, 2014, 2016, and 2018. Data on demographics, sexual behaviors and the laboratory test results of HIV, syphilis, HSV-2 were collected. The χ2 trend test was used to analyze the trends of HIV/syphilis/HSV-2 seropositive rate. The binary logistic regression model was used to explore the factors associated with HSV-2 infection. RESULTS: The seropositive rate of HIV fell significantly from 15.9% in 2012 to 8.7% in 2018 (Ptrend = 0.003), syphilis seropositive rate was significantly decreased from 20.4% in 2012 to 14.8% in 2018 (Ptrend = 0.025), HSV-2 seropositive rate had no significant change (16.7% in 2012 to 14.0% in 2018; Ptrend = 0.617). In principal component logistic regression analysis showed that FAC1_1 (X1 = Ever had sex with female, X2 = Gender of first sexual partner, X3 = Marital status, X4 = Age group), FAC2_1 (X5 = Education, X6 = Monthly income (RMB), X7 = Frequency of condom use in anal sex with men in the past 6 months), and FAC4_1 (X9 = History of STDs) were significantly associated with HSV-2 infection. CONCLUSIONS: The seropositive rates of HIV and syphilis have dropped significantly but are still high. HSV-2 seropositive rate had no significant change and maintained a high level. It is necessary to continue strengthening HIV and syphilis interventions among MSM in Shenzhen. HSV-2 detection and intervention are urgently required for MSM, which might be another effective biological strategy further to control the HIV epidemic among MSM in Shenzhen.

8.
AIDS Res Hum Retroviruses ; 37(7): 523-528, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33913769

RESUMO

Due to the low incidence of concurrent human immunodeficiency virus (HIV) and syphilis infection identified during the early phase, such as window period (WP), little is known about the clinical manifestations, diagnosis, and treatment efficacy at very early stages. One longitudinal study was conducted in a 42-year-old blood donor who was concurrently infected with syphilis and HIV. This blood donor was treated with a penicillin-based regimen and early antiretroviral therapy (ART). Sequential serological and nucleic acid tests were performed and the results were comparatively analyzed. A regular male donor who had two occasions of high-risk sexual behaviors 41 and 35 days before donation donated whole blood at the Shenzhen Blood Center. ART was initiated at the 28th day after donation (DAD), and syphilis treatment was received at the 49th DAD. Microbiological analysis using a fourth-generation anti-HIV enzyme-linked immunosorbent assay (ELISA) (4th GAHE) and electro-chemiluminesent immunoassay indicated a positive signal at the 6th DAD, while a third-generation anti-HIV ELISA (3rd GAHE) showed positive at the 26th DAD. All nucleic acid testing (NAT) for HIV RNA were reactive except the minipool NAT of 6 pooled samples at 117th DAD. The HIV viral load declined more than 4-log in copies per milliliter over 3 months, until reaching nondetectable levels at 246th DAD. Nevertheless, HIV-1 DNA was still detectable at 403rd DAD. Among all methods utilized, anti-treponema pallidum ELISA detected syphilis infection at the earliest time. A successful serological response to syphilis treatment was reached around the 80th DAD. Concurrent infection with syphilis and HIV during early phases did not significantly change the sensitivity of reagents in detection nor alter the therapeutic efficacy for the treatment of both pathogens, but might result in delayed HIV serological WP.


Assuntos
Infecções por HIV , Sífilis , Sorodiagnóstico da AIDS , Adulto , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Longitudinais , Masculino , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico
9.
Biochemistry ; 60(15): 1165-1177, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33792309

RESUMO

Differential scanning calorimetry and differential scanning fluorimetry were used to measure the thermal stability of human retinoid X receptor-α ligand binding domain (RXRα LBD) homodimer in the absence or presence of rexinoid and coactivator peptide, GRIP-1. The apo-RXRα LBD homodimer displayed a single thermal unfolding transition with a Tm of 58.7 °C and an unfolding enthalpy (ΔH) of 673 kJ/mol (12.5 J/g), much lower than average value (35 J/g) of small globular proteins. Using a heat capacity change (ΔCp) of 15 kJ/(mol K) determined by measurements at different pH values, the free energy of unfolding (ΔG) of the native state was 33 kJ/mol at 37 °C. Rexinoid binding to the apo-homodimer increased Tm by 5 to 9 °C and increased the ΔG of the native homodimer by 12 to 20 kJ/mol at 37 °C, consistent with the nanomolar dissociation constant (Kd) of the rexinoids. GRIP-1 binding to holo-homodimers containing rexinoid resulted in additional increases in ΔG of 14 kJ/mol, a value that was the same for all three rexinoids. Binding of rexinoid and GRIP-1 resulted in a combined 50% increase in unfolding enthalpy, consistent with reduced structural fluidity and more compact folding observed in other published structural studies. The complexes of UAB110 and UAB111 are each more stable than the UAB30 complex by 8 kJ/mol due to enhanced hydrophobic interactions in the binding pocket because of their larger end groups. This increase in thermodynamic stability positively correlates with their improved RXR activation potency. Thermodynamic measurements are thus valuable in predicting agonist potency.


Assuntos
Peptídeos/farmacologia , Multimerização Proteica/efeitos dos fármacos , Receptor X Retinoide alfa/química , Concentração de Íons de Hidrogênio , Cinética , Estabilidade Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína/efeitos dos fármacos , Termodinâmica
10.
J Chem Inf Model ; 61(4): 1762-1777, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33720715

RESUMO

Cystic Fibrosis (CF) is caused by mutations to the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. CFTR is composed of two membrane spanning domains, two cytosolic nucleotide-binding domains (NBD1 and NBD2) and a largely unstructured R-domain. Multiple CF-causing mutations reside in the NBDs and some are known to compromise the stability of these domains. The ability to predict the effect of mutations on the stability of the cytosolic domains of CFTR and to shed light on the mechanisms by which they exert their effect is therefore important in CF research. With this in mind, we have predicted the effect on domain stability of 59 mutations in NBD1 and NBD2 using 15 different algorithms and evaluated their performances via comparison to experimental data using several metrics including the correct classification rate (CCR), and the squared Pearson correlation (R2) and Spearman's correlation (ρ) calculated between the experimental ΔTm values and the computationally predicted ΔΔG values. Overall, the best results were obtained with FoldX and Rosetta. For NBD1 (35 mutations), FoldX provided R2 and ρ values of 0.64 and -0.71, respectively, with an 86% correct classification rate (CCR). For NBD2 (24 mutations), FoldX R2, ρ, and CCR were 0.51, -0.73, and 75%, respectively. Application of the Rosetta high-resolution protocol (Rosetta_hrp) to NBD1 yielded R2, ρ, and CCR of 0.64, -0.75, and 69%, respectively, and for NBD2 yielded R2, ρ, and CCR of 0.29, -0.27, and 50%, respectively. The corresponding numbers for the Rosetta's low-resolution protocol (Rosetta_lrp) were R2 = 0.47, ρ = -0.69, and CCR = 69% for NBD1 and R2 = 0.27, ρ = -0.24, and CCR = 63% for NBD2. For NBD1, both algorithms suggest that destabilizing mutations suffer from destabilizing vdW clashes, whereas stabilizing mutations benefit from favorable H-bond interactions. Two triple consensus approaches based on FoldX, Rosetta_lpr, and Rosetta_hpr were attempted using either "majority-voting" or "all-voting". The all-voting consensus outperformed the individual predictors, albeit on a smaller data set. In summary, our results suggest that the effect of mutations on the stability of CFTR's NBDs could be largely predicted. Since NBDs are common to all ABC transporters, these results may find use in predicting the effect and mechanism of the action of multiple disease-causing mutations in other proteins.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Humanos , Transporte de Íons , Mutação
11.
Curr HIV Res ; 19(3): 238-247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33461468

RESUMO

BACKGROUND: The latent reservoir of HIV-1 is a major barrier to achieving the eradication of HIV-1/AIDS. One strategy is termed "shock and kill", which aims to awaken the latent HIV-1 using latency reversing agents (LRAs) to replicate and produce HIV-1 particles. Subsequently, the host cells containing HIV-1 can be recognized and eliminated by the immune response and anti-retroviral therapy. Although many LRAs have been found and tested, their clinical trials were dissatisfactory. OBJECTIVE: To aim of the study was to investigate how resveratrol reactivates silent HIV-1 transcription and assess if resveratrol could be a candidate drug for the "shock" phase in "shock and kill" strategy. METHODS: We used established HIV-1 transcription cell models (HeLa-based NH1 and NH2 cells) and HIV-1 latent cell models (J-Lat A72 and Jurkat 2D10 cells). We performed resveratrol treatment on these cell lines and studied the mechanism of how resveratrol stimulates HIV-1 gene transcription. We also tested resveratrol's bioactivity on primary cells isolated from HIV-1 latent infected patients. RESULTS: Resveratrol promoted HIV-1 Tat protein levels, and resveratrol-induced Tat promotion was found to be dependent on the AKT/FOXO1 signaling axis. Resveratrol could partially dissociate P-TEFb (Positive Transcription Elongation Factor b) from 7SK snRNP (7SK small nuclear Ribonucleoprotein) and promote Tat-SEC (Super Elongation Complex) interaction. Preclinical studies showed that resveratrol potentiated Vorinostat to awaken HIV-1 latency in HIV-1 latent infected cells isolated from patients. CONCLUSION: We found a new mechanism of resveratrol stimulating the production of HIV-1. Resveratrol could be a promising candidate drug to eradicate HIV-1 reservoirs.

12.
Emerg Microbes Infect ; 9(1): 2368-2378, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33151135

RESUMO

Managing recovered COVID-19 patients with recurrent-positive SARS-CoV-2 RNA test results is challenging. We performed a population-based observational study to characterize the viral RNA level and serum antibody responses in recurrent-positive patients and evaluate their viral transmission risk. Of 479 recovered COVID-19 patients, 93 (19%) recurrent-positive patients were identified, characterized by younger age, with a median discharge-to-recurrent-positive length of 8 days. After readmission, recurrent-positive patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in recurrent-positive patients ranged from 1.8 to 5.7 log10 copies/mL (median: 3.2), which was significantly lower than the corresponding values at disease onset. There are generally no significant differences in antibody levels between recurrent-positive and non-recurrent-positive patients, or in recurrent-positive patients over time (before, during, or after recurrent-positive detection). Virus isolation of nine representative specimens returned negative results. Whole genome sequencing of six specimens yielded only genomic fragments. 96 close contacts and 1,200 candidate contacts of 23 recurrent-positive patients showed no clinical symptoms; their viral RNA (1,296/1,296) and antibody (20/20) tests were negative. After full recovery (no longer/never recurrent-positive), 60% (98/162) patients had neutralizing antibody titers of ≥1:32. Our findings suggested that an intermittent, non-stable excretion of low-level viral RNA may result in recurrent-positive occurrence, rather than re-infection. Recurrent-positive patients pose a low transmission risk, a relatively relaxed management of recovered COVID-19 patients is recommended.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , RNA Viral/análise , Adulto , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Feminino , Genoma Viral/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , Recidiva , SARS-CoV-2 , Sequenciamento Completo do Genoma , Adulto Jovem
13.
J Cell Biochem ; 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32830348

RESUMO

Müller cells are closely related to diabetic retinopathy (DR). Aquaporin-4 (AQP4) can effectively promote the diffusion of water across cellular membranes. However, the dynamic balance of water plays key role in many diseases, such as cerebral edema. Meanwhile, the unusual expression and distribution of AQP4 in the retina are the significant causes of ocular hypertension and reperfusion injury. To explore the functional significance between microRNA-320a (miR-320a) and AQP4 in pathological hypoxia-induced DR related retinal edema, we hypothesized that miR-320a regulates AQP4 expression and internalization to relieve the edema of Müller cells under the pathological retinal hypoxia stress by targeting AQP4, thereby attenuate the damage of Müller cells. Results demonstrated that miR-320a mimics inhibited the expressions of AQP4 in Müller cells. Furthermore, overexpression miR-320a protected Müller cells by suppressing superoxide anion. In addition, overexpression miR-320a markedly attenuated hypoxia-induced injury, significantly increased the cell viability, and promoted the internalization of AQP4. Furthermore, miR-320a can also regulate the stable anchoring of AQP4 on the cell membrane. Our study indicated that miR-320a may be a potential modulator which can mediate AQP4 expression and attenuate the hypoxia damage of Müller cells. In conclusion, miR-320a may be a potential target for DR therapy by targeting AQP4.

14.
Sci Rep ; 10(1): 11887, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681141

RESUMO

Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , RNA Viral/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , COVID-19 , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Coronavirus/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/genética , Recidiva , Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto Jovem
15.
Transfusion ; 60(7): 1633-1638, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32358857

RESUMO

BACKGROUND: Discrepancies can occur with the use of clinical human immunodeficiency virus (HIV) diagnostic reagents for the HIV window period (WP; time from RNA to antibody detection by diagnostic or blood screening assays). Antiretroviral therapy (ART) during acute HIV infection can impact HIV-specific antibodies, antigens, and DNA/RNA detection. In this study, an HIV WP blood donor who initiated ART was monitored, evaluating the immunological and nucleic acid testing (NAT) results for early ART and discussing the potential effects on blood safety. STUDY DESIGN AND METHODS: This was a follow-up study of a HIV WP donor detected 36 hours after high-risk sexual behavior, who was subsequently treated with ART. Immunological and NAT methods were comparatively analyzed. RESULTS: The 4th generation HIV serologic assays were positive at Day 11, and the 3rd generation domestic anti-HIV assay was positive at Day 33. Individual donation (ID) NAT and minipool (MP) NAT of six samples were reactive, but 12-sample MP-NAT was nonreactive. ART resulted in a slow decline of HIV RNA, but HIV DNA was still detected on Day 757. CONCLUSION: After ART, ID-NAT was more sensitive than MP-NAT or serologic detection; however, HIV DNA detection was more sensitive, with DNA but not RNA persistently detectable.


Assuntos
Antirretrovirais/administração & dosagem , Doadores de Sangue , Segurança do Sangue , DNA Viral/sangue , Infecções por HIV , RNA Viral/sangue , Adulto , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico
16.
Int J Med Sci ; 17(3): 383-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32132873

RESUMO

Objective: The proportion of hepatitis e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients in China has increased rapidly. However, the response of these patients to peginterferon (peg-IFN) treatment is poor, and the antiviral treatment strategies are inconsistent. This study aimed to investigate the role of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) in early prediction of response in HBeAg-negative CHB patients receiving peg-IFN α-2a. Patients and Methods: Treatment-naïve HBeAg-negative patients were involved in this prospective study during 2014-2018. The HBV DNA and HBsAg were quantified at baseline and during treatment (weeks 12, 24 and 48) in sera. The factors associated with HBV DNA undetectable and HBsAg <100 IU/ml at treatment 48 weeks were assessed. Results: This study involved 45 patients. There was HBV DNA undetectable in 36 cases (80%), including 19 (52.8%) with HBsAg <100 IU/ml at week 48. The HBV DNA <2.0 log10IU/ml at week 24 (PPV = 96.9%, NPV = 66.7%, P = 0.018) was an independent predictor of HBV DNA undetectable at week 48. The HBsAg <800 IU/ml at baseline (PPV = 92.1%, NPV = 69.7%, P = 0.054) and HBsAg decline >5.00-fold at week 24 (PPV = 83.3%, NPV = 77.8%, P = 0.038) were independent predictors of HBsAg <100 IU/ml and HBV DNA undetectable at week 48. Conclusion: Early on-treatment quantification of HBV DNA and HBsAg in patients with HBeAg-negative CHB treated with peg-IFN α-2a may help identify those likely to be cured by this method and optimize therapy strategies.


Assuntos
Antivirais/uso terapêutico , DNA Viral/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
17.
BMJ Open ; 9(8): e028933, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31446409

RESUMO

OBJECTIVES: To investigate the relationship between gay app use and HIV testing among men who have sex with men (MSM). DESIGN: Serial cross-sectional study. SETTING: A newly well-developed city in China. PARTICIPANTS: 4935 MSM were recruited through offline sampling methods from 2015 to 2017. PRIMARY AND SECONDARY OUTCOMES: The primary outcome is the difference in HIV testing between app and non-app users. RESULTS: 2872 (58.2%) and 2159 (43.7%) participated MSM had been tested for HIV within lifetime and the past year, respectively. Compared with non-app-using MSM, app-using MSM had a significantly higher prevalence of HIV testing within lifetime (adjusted OR (AOR): 1.48, 95% CI 1.27 to 1.72) and the past year (AOR: 1.36, 95% CI 1.18 to 1.57). App-using MSM were more likely to take an HIV test at the Centers for Disease Control and Prevention (AOR: 1.48, 95% CI 1.24 to 1.76) and community-based organisations (AOR: 1.71, 95% CI 1.44 to 2.03), but less often at gay venues (AOR: 0.49, 95% CI 0.37 to 0.63). Meanwhile, app-using MSM were more likely to take self-testing (AOR: 1.61, 95% CI 1.21 to 2.14). Predictors of HIV testing in the past year were: having an education level of college or higher (AOR: 1.29, 95% CI 1.01 to 1.65), being self-identified as a homosexual (AOR: 1.23, 95% CI 1.02 to 1.46), being recruited through clinic-based sampling (AOR: 1.30, 95% CI 1.06 to 1.60), using gay app (AOR: 1.49, 95% CI 1.21 to 1.83), engaging in group sex (AOR: 1.64, 95% CI 1.23 to 2.19), having received HIV-related service (AOR: 5.49, 95% CI 4.57 to 6.60), having a high level of HIV-related knowledge (AOR: 1.33, 95% CI 1.10 to 1.61) and high-risk perception (AOR: 2.95, 95% CI 1.40 to 6.23). CONCLUSIONS: Gay app use was significantly associated with increased HIV testing among MSM hard to reach by traditional outreach. Therefore, it is imperative to expand HIV testing among non-app-using MSM. Continued efforts, innovative strategies and increased resource are highly needed to realise the first '90' target.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Aplicativos Móveis/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adulto , China/epidemiologia , Estudos Transversais , Escolaridade , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Humanos , Masculino , Percepção , Prevalência , Fatores de Risco , Adulto Jovem
18.
Sex Transm Infect ; 95(7): 496-504, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30918120

RESUMO

OBJECTIVES: Geosocial networking application specific to men who have sex with men (MSM) (gay app) has revolutionised the social networking of MSM globally, much concern was raised over its linkage to HIV/syphilis risk. This study sought to examine the association between use of gay app and sexual behaviours and HIV/syphilis risk among Chinese MSM. METHODS: Eligible MSM were recruited through combined offline methods from 2015 to 2017 in Shenzhen, China, with data collected including demographics, sexual behaviours, app use, recreational drug use and HIV testing. All participants are required to sign a written informed consent and take a confidential HIV and syphilis testing. RESULTS: The prevalence of app use among non-commercial MSM (NcMSM) has rapidly increased from 12.5% in 2015 to 52.6% in 2017. The primary four apps used were Blued (97.2%), Aloha (18.4%), Jack'd (14.1) and Zank (14.1%). After controlling for confounders, HIV prevalence was still significantly lower among app users than non-app users (adjusted odds ratios [AOR]: 0.77, 95% CI 0.61 to 0.97), yet the lower prevalence of syphilis was not significant (AOR: 0.97, 95% CI 0.76 to 1.23). App-using NcMSM were more likely to be younger, unmarried, self-identified as homosexuality and having higher education level and income than non-app-using NcMSM. App-using NcMSM had higher rate of consistent condom use and HIV testing, higher level of knowledge on HIV/AIDS prevention and condom use; however, they were more likely to have multiple sexual partners, practice receptive role in anal sex and use recreational drug. CONCLUSIONS: App-using NcMSM are more likely to have sexual risk behaviours as well as risk-reduction behaviours such as consistent condom use and HIV testing. Scaled-up and innovative venue-based HIV interventions are warranted for these high-risk MSM frequent social venues with less condom use and fewer HIV tests. Meanwhile, gay app should alternatively serve as an intervention and education platform for the MSM hard-to-reach via venue-based approaches.


Assuntos
Infecções por HIV/epidemiologia , Homossexualidade Masculina , Internet/estatística & dados numéricos , Rede Social , Sífilis/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Adulto Jovem
19.
Lancet Glob Health ; 7(4): e436-e447, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30879508

RESUMO

BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. Previous reviews investigating the role of circumcision in preventing HIV and other STIs among MSM were inconclusive. Many new studies have emerged in the past decade. To inform global prevention strategies for HIV and other STIs among MSM, we reviewed all available evidence on the associations between circumcision and HIV and other STIs among MSM. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, BioMed Central, Scopus, ResearchGate, Cochrane Library, Embase, PsycINFO, Google Scholar, and websites of international HIV and STI conferences for studies published before March 8, 2018. Interventional or observational studies containing original quantitative data describing associations between circumcision and incident or prevalent infection of HIV and other STIs among MSM were included. Studies were excluded if MSM could not be distinguished from men who have sex with women only. We calculated pooled odds ratios (ORs) and their 95% CIs using random-effect models. We assessed risk of bias using the Newcastle-Ottawa scale. FINDINGS: We identified 62 observational studies including 119 248 MSM. Circumcision was associated with 23% reduced odds of HIV infection among MSM overall (OR 0·77, 95% CI 0·67-0·89; number of estimates [k]=45; heterogeneity I2=77%). Circumcision was protective against HIV infection among MSM in countries of low and middle income (0·58, 0·41-0·83; k=23; I2=77%) but not among MSM in high-income countries (0·99, 0·90-1·09; k=20; I2=40%). Circumcision was associated with reduced odds of herpes simplex virus (HSV) infection among MSM overall (0·84, 0·75-0·95; k=5; I2=0%) and penile human papillomavirus (HPV) infection among HIV-infected MSM (0·71, 0·51-0·99; k=3; I2=0%). INTERPRETATION: We found evidence that circumcision is likely to protect MSM from HIV infection, particularly in countries of low and middle income. Circumcision might also protect MSM from HSV and penile HPV infection. MSM should be included in campaigns promoting circumcision among men in countries of low and middle income. In view of the substantial proportion of MSM in countries of low and middle income who also have sex with women, well designed longitudinal studies differentiating MSM only and bisexual men are needed to clarify the effect of circumcision on male-to-male transmission of HIV and other STIs. FUNDING: National Natural Science Foundation of China, National Science and Technology Major Project of China, Australian National Health and Medical Research Council Early Career Fellowship, Sanming Project of Medicine in Shenzhen, National Institutes of Health, Mega Projects of National Science Research for the 13th Five-Year Plan, Doris Duke Charitable Foundation.


Assuntos
Circuncisão Masculina/tendências , Infecções por HIV/prevenção & controle , Herpes Simples/prevenção & controle , Homossexualidade Masculina/estatística & dados numéricos , Doenças Sexualmente Transmissíveis/prevenção & controle , Humanos , Masculino , Comportamento Sexual
20.
J Biol Chem ; 293(46): 17685-17704, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-29903914

RESUMO

Many disease-causing mutations impair protein stability. Here, we explore a thermodynamic strategy to correct the disease-causing F508del mutation in the human cystic fibrosis transmembrane conductance regulator (hCFTR). F508del destabilizes nucleotide-binding domain 1 (hNBD1) in hCFTR relative to an aggregation-prone intermediate. We developed a fluorescence self-quenching assay for compounds that prevent aggregation of hNBD1 by stabilizing its native conformation. Unexpectedly, we found that dTTP and nucleotide analogs with exocyclic methyl groups bind to hNBD1 more strongly than ATP and preserve electrophysiological function of full-length F508del-hCFTR channels at temperatures up to 37 °C. Furthermore, nucleotides that increase open-channel probability, which reflects stabilization of an interdomain interface to hNBD1, thermally protect full-length F508del-hCFTR even when they do not stabilize isolated hNBD1. Therefore, stabilization of hNBD1 itself or of one of its interdomain interfaces by a small molecule indirectly offsets the destabilizing effect of the F508del mutation on full-length hCFTR. These results indicate that high-affinity binding of a small molecule to a remote site can correct a disease-causing mutation. We propose that the strategies described here should be applicable to identifying small molecules to help manage other human diseases caused by mutations that destabilize native protein conformation.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Nucleotídeos de Timina/metabolismo , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Ligação de Hidrogênio , Ligantes , Mutação , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Estabilidade Proteica , Desdobramento de Proteína , Termodinâmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...