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Anti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.
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Autoanticuerpos , Interferón gamma , Micosis , Talaromyces , Células TH1 , Humanos , Talaromyces/inmunología , Células TH1/inmunología , Interferón gamma/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Masculino , Adulto , Femenino , China , Micosis/inmunología , Micosis/microbiología , Persona de Mediana Edad , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/inmunología , Factor de Transcripción STAT1/inmunología , Factor de Transcripción STAT1/genéticaRESUMEN
Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.
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OBJECTIVES: Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians. METHODS: We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022. RESULTS: A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative. CONCLUSION: TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative.
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Infecciones por VIH , Micosis , Talaromyces , Humanos , Micosis/complicaciones , Micosis/diagnóstico , Micosis/microbiología , Micosis/patología , Estudios Retrospectivos , Infecciones por VIH/complicaciones , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
Introduction: Considering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza-Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD. Methods: In this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5-7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza-S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months. Results: Among all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD. Conclusion: The influenza-S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03449459.
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Background: Although anti-IFN-γ autoantibodies predispose patients to Talaromyces marneffei infection, whether this is mediated by T cell attenuation remains elusive. Methods: Total peripheral blood mononuclear cells (PBMCs) from healthy donors or patients with T. marneffei infection were stimulated with M158-66, and immunodominant influenza H1N1 peptide, or heat-inactivated T. marneffei in the presence of serum from anti-IFN-γ autoantibody-positive patients or healthy controls. The percentages of IFN-γ+TNF+CD8+ T cells and IFN-γ+CD4+ T cells were determined by flow cytometry and cytokines released in the supernatant were detected by Cytometric Bead Array. Furthermore, PBMCs from patients with T. marneffei infection and healthy individuals were stimulated with IFN-γ and anti-CD3/CD28 beads, and the levels of STAT1 and STAT3 phosphorylation were detected by Western blot. Results: The M1-reactive CD8+ T cells that expressed IFN-γ+ TNF-α+ of healthy controls were clearly reduced in serum with high-titer anti-IFN-γ autoantibodies. In addition, the CD4+ T cell response, designated by the expression of IFN-γ, against T. marneffei in PBMCs of patients were significantly decreased when cultured in high-titer anti-IFN-γ autoantibody serum culture, compared to the healthy compartments. Moreover, the release of the cytokines IFN-γ, TNF-α and IL-2 was significantly decreased, while IL-10 was significantly increased. There was no significant difference in the phosphorylation levels of STAT1 and STAT3 protein between patients and healthy controls after IFN-γ or anti-CD3/CD28 beads stimulation. Conclusion: Anti-IFN-γ autoantibodies presence in the serum inhibited CD4+ Th1 and CD8+ T cell immune responses. There was no congenital dysfunction of STAT1 and STAT3 in anti-IFN-γ autoantibody-positive patients with T. marneffei infection. These results suggest that the production of anti-IFN-γ autoAbs impair T-lymphocyte responses.
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Background: Diagnosing chronic pulmonary aspergillosis is a major challenge in clinical practice. The development and validation of a novel, sensitive and specific assay for diagnosing chronic pulmonary aspergillosis is urgently needed. Methods: From April 2018 to June 2019, 53 patients with chronic pulmonary aspergillosis (CPA), 32 patients with community-acquired pneumonia (CAP) and 48 healthy controls were recruited from the First Affiliated Hospital of Guangzhou Medical University. Clinical characteristics and samples were collected at enrollment. All exhaled breath samples were analyzed offline using thermal desorption single-photon ionization time-of-flight mass spectrometry; to analyze the metabolic pathways of the characteristic volatile organic compounds, serum samples were subjected to ultrahigh-performance liquid chromatography. Results: We identified characteristic volatile organic compounds in patients with chronic pulmonary aspergillosis, which mainly consisted of phenol, neopentyl alcohol, toluene, limonene and ethylbenzene. These compounds were assessed using a logistic regression model. The sensitivity and specificity were 95.8 and 96.9% for discriminating patients in the CPA group from those in the CAP group and 95.8 and 97.9% for discriminating patients in the CPA group from healthy controls, respectively. The concentration of limonene (m/z 136) correlated significantly positively with anti-Aspergillus fumigatus IgG antibody titers (r = 0.420, P < 0.01). After antifungal treatment, serum IgG and the concentration of limonene (m/z 136) decreased in the subgroup of patients with chronic pulmonary aspergillosis. Conclusions: We identified VOCs that can be used as biomarkers for differential diagnosis and therapeutic response prediction in patients with chronic pulmonary aspergillosis.
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Increasing attention has been directed to Talaromyces marneffei (T. marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. marneffei infection in HIV-negative patients.
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Infecciones por VIH , Talaromyces , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Micosis , EsfingolípidosRESUMEN
BACKGROUND: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China. METHODS: Between January 2018 and September 2020, we enrolled patients with T. marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. RESULTS: Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. CONCLUSION: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.
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Síndromes de Inmunodeficiencia/etiología , Interferón gamma/inmunología , Micosis/inmunología , Adulto , Autoanticuerpos/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Among three monofluoroanilines, 2-fluoroaniline (2-FA) and 3-fluoroaniline (3-FA) exhibit relatively poor biodegradability. This work examined their degradation characteristics in a mixed culture system and also analyzed the microorganism community. After acclimation for 58 d and 43 d, the high removal efficiency of 100% of 2-FA and 95.3% of 3-FA was obtained by adding 25 mg L-1 of 2-FA or 3-FA to the two reactors, respectively. In addition, the high defluorination rates of 2-FA and 3-FA were observed to be 87.0% and 89.3%, respectively. The degradation kinetics showed that the maximum specific degradation rates of 2-FA and 3-FA were (21.23 ± 0.91) mg FA (gâ¢VSS·h)-1, and (11.75 ± 0.99) mg FA (gâ¢VSS·h)-1, respectively. PCR-DGGE analysis revealed that the unique bacteria degrading 2-FA were mainly composed of six genera (Novosphingobium, Bradyrhizobium, Aquaspirillum, Aminobacter, Ochrobactrum, and Labrys), and five genera that degraded 3-FA (Ochrobactrum, Aquaspirillum, Lachnobacterium, Bradyrhizobium, and Variovorax). Analysis of the key catabolic enzyme activities indicated that the simultaneous hydroxylation and dehalogenation were involved in monooxygenase elimination of 2-FA and conversion of 3-FA to 4-fluorocatechol by dioxygenase, indicating that enriched mixed cultures were effective to metabolize 2-FA or 3-FA by unconventional pathways to prevent the accumulation of toxic metabolites.
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Compuestos de Anilina/metabolismo , Fluorobencenos/metabolismo , Microbiota , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Biodegradación Ambiental , Reactores Biológicos/microbiología , Halogenación , Hidroxilación , Cinética , Microbiota/genéticaRESUMEN
The interest of fluoroanilines in the environment is due to their extensive applications in industry and their low natural biodegradability. A pure bacterial strain capable of degrading 3-fluoroaniline (3-FA) as the sole source of carbon and energy was isolated from a sequencing batch reactor operating for the treatment of 3-FA. The strain (designated as JF-3) was identified by 16S rRNA gene analysis as a member of the genus Rhizobium. When grown in 3-FA medium at concentrations of 100-700 mg/L, strain JF-3 almost completely removed 3-FA within 72 h. However, the obvious cell growth inhibition was observed in cultures treated with 3-FA concentrations greater than 500 mg/L. The degradation kinetics of 3-FA were consistent with Haldane's model with the maximum degradation rate as 67.66 mg/(g dry cell h). The growth kinetics of strain JF-3 followed Andrew's model with the maximum growth rate as 30.87 h-1. Also, strain JF-3 was able to degrade 4-fluoroaniline, aniline, and catechol, but hardly grew on 2-fluoroaniline, 2,4-dfluoroaniline, 2,3,4-trifluoroaniline, 3-fluorocatechol, and 4-fluorocatechol. Additionally, it was able to grow over a wide pH range (pH 6-10), and also showed tolerance to salinity with lower than 1.0%. This result, in combination with the enzyme assays and analysis of metabolite intermediates, indicated an unconventional pathway for 3-fluoroaniline metabolism that involved conversion to 3-aminophenol and resorcinol by monooxygenase, and which was subsequently metabolized via the ortho-cleavage pathway. To our knowledge, this is the first report on the utilization of 3-FA as a growth substrate by Rhizobium sp.
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Hidrocarburos Aromáticos , Rhizobium , Biodegradación Ambiental , Cinética , ARN Ribosómico 16SRESUMEN
A series of novel quinolone derivatives (8a-j) were synthesized, and their anticancer activities were tested in human cancer cell lines, human lung carcinoma cell (A549), human promyelocytic leukemia cell (HL-60), and human cervical cancer cell (Hela). Compound 8i was found to be 5-times more potent in cell-killing activity for cell lines A549, HL-60, and Hela than the positive control irinotecan or cisplatin, with IC50 of 0.009, 0.008 and 0.010 µM, respectively. The docking study revealed that compound 8i might have strong interactions with the active site of DNA-topoisomerase I.
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Antineoplásicos/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , Simulación del Acoplamiento Molecular , Quinolonas/farmacología , Inhibidores de Topoisomerasa I/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Quinolonas/síntesis química , Quinolonas/química , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I/síntesis química , Inhibidores de Topoisomerasa I/químicaRESUMEN
With the continuous development of DNA extraction and testing technology, the DNA left at a crime scene plays a decisive role in the determination of criminal suspects in criminal investigation. But in the meanwhile, the anti-reconnaissance awareness of suspect is growing, which leads to a decrease of evidence left at scene during and after a crime. Therefore, in the process of evidence collection at scene, the finding and extraction of touch biological evidence, and the DNA detection are more and more important. At present, the proportion of touch evidence at the crime scene increases, which plays an increasingly important role in the detection of cases. However, with the characteristics of minute quantities, small size and secrecy, these touch evidence is difficult to be observed. What's more, various forms of pollution at the scene greatly accelerate the degradation rate of trace material, thus, the test and analysis of such material has become the emphasis and difficulty of the forensic evidence identification. This article reviews different kinds, collection and extraction methods of touch DNA, the factors that affect the detection and the problems may meet in the detection for providing an application prospect to the forensic practice.
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Humanos , Crimen , Criminales , ADN/aislamiento & purificación , Dermatoglifia del ADN , Genética Forense/métodos , TactoRESUMEN
Objective Construct a mRNA multiplex amplification system to identify different types of semen stains. Methods First, collect normal, oligozoospermia and azoospermia semen samples to make semen stains. Second, extract total RNA with Qiagen RNeasy Micro Kit. Then use reverse transcript PCR to amplify goal mRNA markers: 2 markers for sperm(PRM1, PRM2), 2 markers for seminal plasma(TGM4, SEMG1) and 2 housekeeping genes(TEF, UCE). Results All semen mRNA markers can be detected in normal semen samples. The RFU of sperm mRNA markers are lower in oligozoospermia semen samples than that in normal controls. No sperm mRNA markers can be detected in the azoospermia semen samples, only seminal plasma specific can be detected. Conclusion The differentiation of normal and azoospermia semen can be achieved by using multiplex mRNA fluorescence amplification system. While normal semen and oligozoospermia semen compared to no statistical difference.
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BACKGROUND: Since the identification in early 2013 of severe disease caused by influenza A(H7N9) virus infection, there have been few attempts to characterize the full severity profile of human infections. Our objective was to estimate the number and severity of H7N9 infections in Guangzhou, using a serological study. METHODS: We collected residual sera from patients of all ages admitted to a hospital in the city of Guangzhou in southern China in 2013 and 2014. We screened the sera using a haemagglutination inhibition assay against a pseudovirus containing the H7 and N9 of A/Anhui/1/2013(H7N9), and samples with a screening titer ≥10 were further tested by standard hemagglutination-inhibition and virus neutralization assays for influenza A(H7N9). We used a statistical model to interpret the information on antibody titers in the residual sera, assuming that the residual sera provided a representative picture of A(H7N9) infections in the general population, accounting for potential cross-reactions. RESULTS: We collected a total of 5360 residual sera from December 2013 to April 2014 and from October 2014 to December 2014, and found two specimens that tested positive for H7N9 antibody at haemagglutination inhibition titer ≥40 and a neutralization titer ≥40. Based on this, we estimated that 64,000 (95 % credibility interval: 7300, 190,000) human infections with influenza A(H7N9) virus occurred in Guangzhou in early 2014, with an infection-fatality risk of 3.6 deaths (95 % credibility interval: 0.47, 15) per 10,000 infections. CONCLUSIONS: Our study suggested that the number of influenza A(H7N9) virus infections in Guangzhou substantially exceeded the number of laboratory-confirmed cases there, albeit with considerable imprecision. Our study was limited by the small number of positive specimens identified, and larger serologic studies would be valuable. Our analytic framework would be useful if larger serologic studies are done.
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Anticuerpos Antivirales/sangre , Aves/virología , Subtipo H7N9 del Virus de la Influenza A/inmunología , Subtipo H7N9 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/inmunología , Gripe Humana/virología , Adolescente , Adulto , Anciano , Animales , Anticuerpos Antivirales/inmunología , Niño , Preescolar , China/epidemiología , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Recién Nacido , Gripe Aviar/epidemiología , Gripe Aviar/inmunología , Gripe Aviar/virología , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
The identiifcation of body lfuid and their tissue resource is an important part of forensic medicine research. Conventional methods have imperfections like high false positive rate and may destroy biomaterial, which should be replaced by a new conifrmatory test. Highly-differentiated cells express speciifc mRNA molecules that can be used for body lfuid identiifcation. These mRNA markers can identify body lfuids like peripheral blood, menstrual blood, semen, saliva, vaginal secretion, skin-contact stains. This method have favorable sensitivity, speciifcity and can be detected after years, made it a ideal way to identify current body lfuids in the future. This review focus on the application of mRNA in body lfuid identiifcation and tissue resource.
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Virus de la Influenza A/genética , Gripe Aviar/virología , Aves de Corral/virología , Animales , China , Humanos , Virus de la Influenza A/patogenicidad , Gripe Aviar/epidemiología , Gripe Aviar/genética , Gripe Aviar/patología , Gripe Humana/epidemiología , Gripe Humana/genética , Gripe Humana/patología , Zoonosis/genética , Zoonosis/patologíaRESUMEN
BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014).
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Antivirales/uso terapéutico , Gripe Humana/terapia , Medicina Tradicional China , Oseltamivir/uso terapéutico , Fitoterapia , Adulto , Protocolos Clínicos , Método Doble Ciego , Humanos , Gripe Humana/tratamiento farmacológico , Persona de Mediana EdadRESUMEN
The fate of fluorinated compounds in the environment, especially polyfluorinated aromatics, is a matter of great concern. In this work, 4-Fluoroaniline (4-FA), 2,4-Difluoroanilines (2,4-DFA), and 2,3,4-Trifluoroanilines (2,3,4-TFA), were chosen as the target pollutants to study their biodegradability under aerobic conditions. The required enriched time of the mixed bacterial culture for degrading 4-FA, 2,4-DFA, and 2,3,4-TFA was 26, 51, and 165 days, respectively, which suggested that the longer enrichment time was required with the increase of fluorine substitution. At the initial concentrations of 100-200 mg L(-1), the 4-FA, 2,4-DFA, and 2,3,4-TFA could be degraded completely by the mixed bacterial culture. The maximum specific degradation rates of 4-FA, 2,4-DFA, and 2,3,4-TFA were 22.48 ± 0.55, 15.27 ± 2.04, and 8.84 ± 0.93 mg FA (g VSS h)(-1), respectively. Also, the three FAs enriched cultures showed certain potential of degrading other two FAs. The results from enzyme assay suggested the expression of meta-cleavage pathways during three FAs degradation. The denaturing gradient gel electrophoresis analysis revealed that unique bacterial communities were formed after FAs enrichment and these were principally composed of ß-Proteobacteria, Oscillatoriophycideae, δ-Proteobacteria, α-Proteobacteria, Thermales, Xanthomonadales, Deinococci, Flavobacteriia, and Actinobacteridae. The Shannon-Wiener indexes in three FAs enriched culture decreased with the increase of fluorine substitution, indicating the significant effect of fluorine substitution on the microbial diversity. These findings supply important information on the fate of three FAs under aerobic environment, and the bacterial communities in their degradation systems.