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BACKGROUND: In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. METHODS: Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1ß, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4+T subsets were measured. RESULTS: A significantly higher IL-18 level in plasma and MM level of CD4+T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MMhigh phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4+T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4+T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. CONCLUSION: An increase in MM was associated with heightened sensitivity of CD4+T cells to pyroptosis, even in early differentiated and inactivated CD4+T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy.
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Infecções por HIV , HIV-1 , Humanos , Caspase 1 , Linfócitos T , Interleucina-18 , Infecções por HIV/tratamento farmacológicoRESUMO
Piezocatalysis has increasingly gained prominence due to its enormous potential for addressing energy shortages and environmental pollution issues. Nonetheless, the low piezocatalytic activity of state-of-the-art materials seriously inhibits the practical applications of piezocatalysis. Here, it is proposed to greatly enhance the piezocatalytic activity for a perovskite ferroelectric, i.e., Sm-doped 0.68Pb(Mg1/3 Nb2/3 )-0.32PbTiO3 (Sm-PMN-PT, a solid solution with ultrahigh piezoelectricity), by introducing oxygen vacancies (OVs). The results show that the presence of OVs promotes the production of reactive oxygen species while enhancing the adsorption and activation of organic pollutants to improve piezocatalytic performance. The OV-Sm-PMN-PT is found to possess a superior piezocatalytic degradation rate constant of 0.073 min-1 under ultrasonic vibration, which is ≈4.9 times higher than that of pristine Sm-PMN-PT. Furthermore, the OV-Sm-PMN-PT can efficiently remove RhB under 400 rpm stirring, making it a promising candidate for water purification using low-frequency mechanical energy from nature. This research sheds light on the design of piezocatalytic materials via defect engineering.
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The impact of hepatitis B virus (HBV) infection on clinical outcomes of coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study is to explore this impact. For this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (VIP), and Wan Fang database for articles between 1 January 2020 and 1 February 2023. We used the Newcastle-Ottawa Quality Assessment to evaluate the study's quality. A random-effects meta-analysis was performed utilising the rates of severe/critical illness and death in COVID-19 patients with and without HBV infection. Eighteen studies with a total of 40,502 participants met the inclusion criteria. The meta-analysis showed that compared to those without HBV infection, COVID-19 patients with HBV were at increased risk of mortality (OR = 1.65, I2 = 58%, and 95% CI 1.08-2.53) and severity (OR = 1.90, I2 = 44%, and 95% CI 1.62-2.24). The region and gender may influence the outcomes of COVID-19 patients with HBV infection, but it requires more global data to confirm. In conclusion, HBV infection is significantly linked to an increased risk of severity and mortality in COVID-19.
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COVID-19 , Hepatite B , Humanos , Vírus da Hepatite B , Hepatite B/complicações , Hepatite B/epidemiologia , ChinaRESUMO
BACKGROUND: In March 2020, the WHO declared the novel coronavirus outbreak a global pandemic. While great success in coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategies in Beijing, China. METHODS: This retrospective study included all imported cases transferred to Beijing Ditan Hospital from 29 February to 20 March 2020 who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at the initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging, were collected and analysed. RESULTS: In total, 2545 cases were included, among which 71 (2.8%) were finally diagnosed with laboratory-confirmed COVID-19. The majority 63 (88.7%) were from Europe. The most common initial symptoms were cough and fever, which accounted for 49.3% and 42.3%, respectively. Only four cases (5.6%) had lymphocytopenia, and thirteen cases (18.3%) demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). At initial presentation, among the 71 confirmed cases, 59 (83.1%) had a positive RT-PCR assay, and 35 (49.3%) had a positive chest CT. Twelve (16.9%) had a negative RT-PCR assay but a positive chest CT. CONCLUSIONS: A combination of RT-PCR and chest CT is an effective strategy for the screening of imported COVID-19 cases. Our findings provide important information and clinical evidence about the infection control of imported COVID-19 cases.
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COVID-19 , Pequim/epidemiologia , China/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
Dielectric ceramics are highly desired for electronic systems owing to their fast discharge speed and excellent fatigue resistance. However, the low energy density resulting from the low breakdown electric field leads to inferior volumetric efficiency, which is the main challenge for practical applications of dielectric ceramics. Here, we propose a strategy to increase the breakdown electric field and thus enhance the energy storage density of polycrystalline ceramics by controlling grain orientation. We fabricated high-quality <111>-textured Na0.5Bi0.5TiO3-Sr0.7Bi0.2TiO3 (NBT-SBT) ceramics, in which the strain induced by the electric field is substantially lowered, leading to a reduced failure probability and improved Weibull breakdown strength, on the order of 103 MV m-1, an ~65% enhancement compared to their randomly oriented counterparts. The recoverable energy density of <111>-textured NBT-SBT multilayer ceramics is up to 21.5 J cm-3, outperforming state-of-the-art dielectric ceramics. The present research offers a route for designing dielectric ceramics with enhanced breakdown strength, which is expected to benefit a wide range of applications of dielectric ceramics for which high breakdown strength is required, such as high-voltage capacitors and electrocaloric solid-state cooling devices.
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BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.
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Brucelose , Linfócitos T Reguladores , Citocinas , Fatores de Transcrição Forkhead , Humanos , Proteínas de Checkpoint Imunológico , Leucócitos MononuclearesRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription-polymerase chain reaction (RT-PCR) method has limitations for clinical diagnosis and treatment. METHODS: A total of 323 samples from 76 COVID-19-confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based 2 target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging. RESULTS: In 95 samples that tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy number of ddPCR (ORF1ab gene, R2â =â 0.83; N gene, R2â =â 0.87). Four (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral loads ranging from 11.1 to 123.2 copies/test. The viral load of respiratory samples was then compared and the average viral load in sputum (17â 429â ±â 6920 copies/test) was found to be significantly higher than in throat swabs (2552â ±â 1965 copies/test, Pâ <â .001) and nasal swabs (651â ±â 501 copies/test, Pâ <â .001). Furthermore, the viral loads in the early and progressive stages were significantly higher than that in the recovery stage (46â 800â ±â 17â 272 vs 1252â ±â 1027, Pâ <â .001) analyzed by sputum samples. CONCLUSIONS: Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.
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Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Adulto , COVID-19 , Testes Diagnósticos de Rotina/métodos , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sistema Respiratório/virologia , SARS-CoV-2 , Testes Sorológicos/métodos , Escarro/virologia , Carga Viral/métodosRESUMO
BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.
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Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Imunidade Humoral/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Adulto , Sequência de Aminoácidos , Anticorpos Antivirais/imunologia , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase/métodos , SARS-CoV-2RESUMO
BACKGROUND: Pertussis, caused by Bordetella pertussis (B. pertussis), is a highly transmissible, acute respiratory disease that occurs in many countries. Diagnosis of pertussis continues to be a challenge using traditional tests due to their turn-around time and sensitivity. Herein, we rapidly and accurately screened a family cluster of pertussis from a child and her mother. METHODS: We used an automated nested multiplex PCR system which included B. pertussis, influenza A virus, and 19 other respiratory pathogens. RESULTS: We detected B. pertussis, influenza A virus H1-2009 (FluA-2009), adenovirus, and respiratory syncytial virus (RSV) in the child, and the mother of the child was positive for B. pertussis and FluA-2009. CONCLUSIONS: Active and timely screening for pertussis of adult family members should be considered. The detection of multiple respiratory pathogens may guide effective antibiotic therapies. This could be a novel test for the prevention of pertussis.
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Adenoviridae/isolamento & purificação , Antibacterianos , Antivirais/administração & dosagem , Bordetella pertussis/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Vírus Sinciciais Respiratórios/isolamento & purificação , Coqueluche , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/fisiopatologia , Coinfecção/terapia , Hotspot de Doença , Saúde da Família , Feminino , Hospitalização , Humanos , Lactente , Técnicas Microbiológicas/métodos , Índice de Gravidade de Doença , Coqueluche/diagnóstico , Coqueluche/microbiologia , Coqueluche/fisiopatologia , Coqueluche/terapiaRESUMO
BACKGROUND: Tuberculosis is one of the main infectious diseases threatening human health, especially in HIV co-infected patients. Xpert® MTB/RIF assay amplifies the rpoB gene of MTB was recommended by the World Health Organization as the initial diagnostic test in cases of suspected infections with Mycobacterium tuberculosis (MTB) or HIV-coinfected TB. METHODS: A 44-year-old male HIV-positive patient co-infected with MTB presented with low-grade fever for 3 months. Rifampicin (RIF) resistance was detected in the celiac pus but not in the pleural effusion using Xpert® MTB/RIF assay. The same samples were then sequenced by next-generation sequencing (NGS) and in-house PCR for rpoB gene. RESULTS: The results of NGS and in-house PCR, however, were paradoxical in the same samples with low or no mutation sequences of RIF resistance. The patient's tuberculosis (TB) therapy was optimized based on first-line anti-TB drugs and antiretroviral treatment. The patient improved with this therapy. CONCLUSIONS: Even with high specificity, false positive results remain possible and RIF resistance detection by Xpert must be considered for clinical interpretation.
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Antibióticos Antituberculose , Infecções por HIV , Mycobacterium tuberculosis , Adulto , Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Testes Diagnósticos de Rotina , Farmacorresistência Bacteriana/genética , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Sensibilidade e Especificidade , EscarroRESUMO
Previous studies have shown that the CareStart™ G6PD Deficiency rapid diagnostic test has high diagnostic accuracy on G6PD deficiency in Africa and Thailand, but not in China. As there are regional differences of G6PD genotype distribution, we are attending to verify the effectiveness of the kit in Chinese population. The study cohort included 247 newborns admitted to our hospital for jaundice. The quantitative detection of G6PD enzyme activity and G6PD gene mutations analysis was used to classify the status of G6PD deficiency. The performance of CareStart™ assays was verified by calculating the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) based on the corrected G6PD deficiency status. In male newborns, the sensitivity of the CareStart™ assay was 98.9%, the specificity was 94.2% and the AUC was 0.97. In female newborns, the sensitivity was 58.5% when the cutoff value of residual enzyme activity was 100%; however, the sensitivity was 100% when the cutoff value was 60%. Therefore, the CareStart™ test can effectively screen G6PD deficiency in male newborns and female infants with less than 60% residual enzyme activity, female infants with residual enzyme activities of 60-100% are more likely to be missed diagnosed among Chinese newborns.
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Testes Diagnósticos de Rotina/normas , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Reação em Cadeia da Polimerase/métodos , Povo Asiático , China/epidemiologia , Testes Diagnósticos de Rotina/métodos , Feminino , Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/etnologia , Humanos , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeAssuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Fezes/virologia , Faringe/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Escarro/virologia , Adolescente , Adulto , Idoso , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Criança , Técnicas de Laboratório Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , SARS-CoV-2 , Carga Viral , Adulto JovemRESUMO
A comprehensive immune landscape for Brucella infection is crucial for developing new treatments for brucellosis. Here, we utilized single-cell RNA sequencing (scRNA-seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute (n = 10), sub-acute (n = 9), and chronic (n = 10) phases as well as six healthy donors. Enzyme-linked immunosorbent assays were applied for validation within this cohort. Brucella infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of S100A8/A9, primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9-TLR4-MyD88 signaling pathway. Moreover, monocytic myeloid-derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN-γ and Th1 signatures as well as a high exhausted state. Additionally, Brucella infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen-presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8+ T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of Brucella at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection.
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Cartilage repair is a significant clinical issue due to its restricted ability to regenerate and self-heal after cartilage lesions or degenerative disease. Herein, a nano-elemental selenium particle (chondroitin sulfate Aselenium nanoparticle, CSA-SeNP) is developed by the supramolecular self-assembly of Na2SeO3 and negatively charged chondroitin sulfate A (CSA) via electrostatic interactions or hydrogen bonds followed by in-situ reducing of l-ascorbic acid for cartilage lesions repair. The constructed micelle exhibits a hydrodynamic particle size of 171.50 ± 2.40 nm and an exceptionally high selenium loading capacity (9.05 ± 0.03 %) and can promote chondrocyte proliferation, increase cartilage thickness, and improve the ultrastructure of chondrocytes and organelles. It mainly enhances the sulfation modification of chondroitin sulfate by up-regulating the expression of chondroitin sulfate 4-O sulfotransferase-1, -2, -3, which in turn promotes the expression of aggrecan to repair articular and epiphyseal-plate cartilage lesions. The micelles combine the bio-activity of CSA with selenium nanoparticles (SeNPs), which are less toxic than Na2SeO3, and low doses of CSA-SeNP are even superior to inorganic selenium in repairing cartilage lesions in rats. Thus, the developed CSA-SeNP is anticipated to be a promising selenium supplementation preparation in clinical application to address the difficulty of healing cartilage lesions with outstanding repair effects.
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Cartilagem Articular , Selênio , Ratos , Animais , Sulfatos de Condroitina/metabolismo , Selênio/metabolismo , Cartilagem/metabolismo , Agrecanas/metabolismo , Condrócitos/metabolismo , Cartilagem Articular/metabolismoRESUMO
Introduction: In November 2021, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was identified as the variant of concern and has since spread globally, replacing other cocirculating variants. To better understand the dynamic changes in viral load over time and the natural history of the virus infection, we analyzed the expression of the open reading frames 1ab (ORF1ab) and nucleocapsid (N) genes in patients infected with Omicron. Methods: We included patients initially admitted to the hospital for SARS-CoV-2 infection between November 5 and December 25, 2022. We collected daily oropharyngeal swabs for quantitative reverse transcriptase-polymerase chain reaction tests using commercial kits. We depicted the cycle threshold (Ct) values for amplification of ORF1ab and N genes from individual patients in age-specific groups in a time series. Results: A total of 480 inpatients were included in the study, with a median age of 59 years (interquartile range, 42 to 78; range, 16 to 106). In the <45-year-old age group, the Ct values for ORF1ab and N gene amplification remained below 35 for 9.0 and 11.5 days, respectively. In the ≥80-year-old age group, the Ct values for ORF1ab and N genes stayed below 35 for 11.5 and 15.0 days, respectively, which was the longest among all age groups. The Ct values for N gene amplification took longer to rise above 35 than those for ORF1ab gene amplification. Conclusion: The time to test negative varied among different age groups, with viral nucleic acid shedding taking longer in older age groups compared to younger age groups. As a result, the time to resolution of Omicron infection increased with increasing age.
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Introduction: Integrase strand transfer inhibitors (INSTIs) are important drugs that are currently used as the first line treatment for HIV-1 patients. The aim of this study was to characterize HIV-1 INSTI mutations among ART-naive patients in Beijing from 2019-2021. Methods: 865 ART-naive patients were enrolled in this study between January 2019 and June 2021 in Beijing. The amplification of the entire pol gene containing the reverse transcriptase, protease and integrase regions was performed using a validated In-house SBS method. HIV-1 subtypes and circulating recombinant forms (CRFs) were determined using the COMET online tool (http://comet.retrovirology.lu). Stanford HIV-1 drug resistance database (HIVdb version 8.9) was used to analyze the mutations. Results: 865 HIV-1 pol sequences were successfully amplified and sequenced. Among them, no major INSTI-related mutations were identified, but 12 polymorphic accessory mutations were found. Two patients have E138A and G163R mutations respectively and both could cause low-level resistance to RAL and EVG. Furthermore, one patient having S230R mutation resulted in low-level resistance to RAL, EVG, DTG and BIC. Conclusion: The prevalence of INSTIs mutations remains low, which demonstrated that INSTIs have good applicability currently in our city. Nevertheless, it is very important to monitor the INSTI-related mutations in Beijing.
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BACKGROUND: Evidence of lymphopoiesis, exhaustion, and premature aging in Chinese patients with human immunodeficiency virus (HIV) is very limited. OBJECTIVE: To assess biological aging and immune senescence in Chinese healthy controls (HC) and ART-naïve HIV-infected men who have sex with men (MSM). METHODS: This case-control study was conducted in Beijing Ditan Hospital from March 2018 to June 2019. The percentages of naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated memory (TemRA) subsets of CD4 and CD8 T cells were studied, along with markers of senescence (CD28-CD57+) and activation (HLA-DR+). Telomere length of naïve (CD45RA+) and memory (CD45RO+) CD8 T cells were quantified by real-time PCR. RESULTS: A total of 26 HIV-infected and 20 age-matched HC MSM were included. Compared to the HC group, the CD4/CD8 ratio of the HIV-infected group was significantly reduced (0.30 vs. 1.70, P<0.001); significant differences emerged among all CD8 but not CD4 T cell subsets (all P<0.05). In the HIV-infected group, the percentages of senescent cells (CD28-CD57+) in TN, TCM, TEM, and TemRA subsets of CD8 T cells were higher (all P<0.05); while a significant difference was only found in naïve CD4 T cells (P<0.05). HLA-DR expression was increased significantly in all CD4 and CD8 T cell subsets. Both naïve (CD45RA+) and memory (CD45RO+) CD8 T cells in this population had significantly shorter telomere lengths (P<0.01) compared to the HC group. CONCLUSION: HIV-infected MSM exhibit signs of accelerated immune senescence and biological aging, which particularly affects the CD8 T-cell subsets.
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Infecções por HIV , Minorias Sexuais e de Gênero , Envelhecimento , Antígenos CD28 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Estudos de Casos e Controles , China/epidemiologia , Antígenos HLA-DR/análise , Homossexualidade Masculina , Humanos , Antígenos Comuns de Leucócito , Masculino , Subpopulações de Linfócitos TRESUMO
INTRODUCTION: Repeat positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following COVID-19 initial viral clearance (re-positivity) poses a public health management challenge. The objective was to determine factors associated with neutralizing antibody (Nab) level and re-positivity among patients infected with a single strain SARS-CoV-2. METHODS: During a single strain SARS-CoV-2 cluster in Beijing, China, longitudinal individual clinical, virological, and immunological data were collected from 368 infections from June 13 to September 22, 2020. Factors associated with Nab level and re-positivity were analyzed using generalized estimating equations. RESULTS: A total of 353 (96%) SARS-CoV-2 infections had demographic, clinical, and laboratory data available. Among the 353 infections, 55 (15.5%) were re-positive, and blood draws were taken from 346 individuals (98.0%) during hospitalization and/or during the follow-up period. Symptoms were milder for the second-time admission for the re-positives, although 36.4% of re-positives presented with radiographic appearance of pneumonia manifestation. Compared to non-re-positive patients, NAb titers were lower among re-positives; NAb was positively associated with clinical severity. Samples from the lower respiratory tract manifested higher viral load than that from the upper respiratory tract. Multivariable analysis showed re-positivity was positively associated with being female [odd ratio (OR)=1.7, 95% confidence interval (CI) 1.1-2.8] and being aged <18 years (OR=5.2, 95% CI 1.5-18.1); having initially asymptomatic infection (OR=13.7, 95% CI 1.6-116.3); and negatively associated with a higher NAb level (OR=0.9, 95% CI 0.5-1.7). CONCLUSIONS: NAb may be important for sustained viral clearance. Lower respiratory tract infection was associated with higher viral load among all infections when compared to upper respiratory tract infection. Continuous lower respiratory and intermittent upper respiratory viral shedding among COVID-19 infections may occur.
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PURPOSE: Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment. PATIENTS AND METHODS: Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array. RESULTS: In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05). CONCLUSION: Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.
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ABSTRACT: It is presently unknown whether imported cases of the 2019 coronavirus disease (COVID-19) have different characteristics when compared with local cases. To compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad.This was a retrospective study of confirmed cases of COVID-19 admitted at the Beijing Ditan Fever Emergency Department between February 29th, 2020, and March 27th, 2020. The clinical characteristics of the patients were compared between local and imported cases.Compared with local cases, the imported cases were younger (27.3â±â11.7 vs. 43.6â±â22.2âyears, Pâ<â.001), had a shorter interval from disease onset to admission (1.0 (0.0-2.0) vs 4.0 (2.0-7.0) days, Pâ<â.001), lower frequencies of case contact (17.4% vs 94.1%, Pâ<â.001), fever (39.1% vs 82.4%, Pâ<â.001), cough (33.3% vs 51.0%, Pâ=â.03), dyspnea (1.9% vs 11.8%, Pâ=â.01), fatigue (7.5% vs. 27.5%, Pâ=â0.001), muscle ache (4.7% vs. 25.5%, Pâ<â0.001), and comorbidities (Pâ<â.05). The imported cases were less severe than the local cases, with 40.4% versus 5.9% mild cases, 2.8% versus 15.7% severe cases, and no critical cases (Pâ<â.001). The length of hospital stay was longer in imported cases than in local cases (32.3â±â14.5 vs 21.7â±â11.2âdays, Pâ<â.001). The imported cases showed smaller biochemical perturbations than the local cases. More imported cases had no sign of pneumonia at computed tomography (45.0% vs 14.9%, Pâ=â.001), and none had pleural effusion (0% vs 14.9%, Pâ<â.001).Compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs.