RESUMO
Microbial inoculation plays a significant role in promoting the efficiency of biowaste conversion. This study investigates the function of Streptomyces-Bacillus Inoculants (SBI) on carbon (C) and nitrogen (N) conversion, and microbial dynamics, during cow manure (10% and 20% addition) and corn straw co-composting. Compared to inoculant-free controls, inoculant application accelerated the compost's thermophilic stage (8 vs 15 days), and significantly increased compost total N contents (+47%) and N-reductase activities (nitrate reductase: +60%; nitrite reductase: +219%). Both bacterial and fungal community succession were significantly affected by DOC, urease, and NH4+-N, while the fungal community was also significantly affected by cellulase. The contribution rate of Cupriavidus to the physicochemical factors of compost was as high as 83.40%, but by contrast there were no significantly different contributions (â¼60%) among the top 20 fungal genera. Application of SBI induced significant correlations between bacteria, compost C/N ratio, and catalase enzymes, indicative of compost maturation. We recommend SBI as a promising bio-composting additive to accelerate C and N turnover and high-quality biowaste maturation. SBI boosts organic cycling by transforming biowastes into bio-fertilizers efficiently. This highlights the potential for SBI application to improve plant growth and soil quality in multiple contexts.
Assuntos
Carbono , Compostagem , Nitrogênio , Streptomyces , Streptomyces/metabolismo , Nitrogênio/metabolismo , Carbono/metabolismo , Esterco , Bacillus/metabolismo , Bactérias/metabolismoRESUMO
BACKGROUND: Blueberry is one of the most important fruit crops worldwide. Anthocyanin is an important secondary metabolites that affects the appearance and nutritive quality of blueberries. However, few studies have focused on the molecular mechanism underlying anthocyanin accumulation induced by light intensity in blueberries. RESULTS: The metabolic analysis revealed that there were 134 significantly changed metabolites in the natural light compared to the control, and flavone, flavonol, and anthocyanins were the most significantly increased. Transcriptome analysis found 6 candidate genes for the anthocyanin synthesis pathway. Quantitative reverse transcription PCR (qRT-PCR) results confirmed changes in the expression levels of genes encoding metabolites involved in the flavonoid synthesis pathways. The flavonoid metabolic flux in the light intensity-treatment increased the accumulation of delphinidin-3-O-arabinoside compared to under the shading-treatment. Furthermore, we performed qRT-PCR analysis of anthocyanin biosynthesis genes and predicted that the gene of VcF3'5'H4 may be a candidate gene for anthocyanin accumulation and is highly expressed in light intensity-treated fruit. Through the co-expression analysis of transcription factors and anthocyanin synthesis pathway genes, we found that the VcbHLH004 gene may regulate VcF3'5'H4, and then we transformed VcbHLH004 heterologously into tomato to verify its function. CONCLUSION: These results provide novel insights into light intensity regulation of blueberry anthocyanin accumulation and represent a valuable data set to guide future functional studies and blueberry breeding.
Assuntos
Mirtilos Azuis (Planta) , Vaccinium , Antocianinas/metabolismo , Mirtilos Azuis (Planta)/genética , Mirtilos Azuis (Planta)/metabolismo , Flavonoides/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Metaboloma , Vaccinium/genética , Vaccinium/metabolismoRESUMO
Long non-coding RNAs (lncRNAs) are vital regulators of different biological processes during bronchopulmonary dysplasia (BPD). This study was conducted to probe the biological roles of lncRNA CASC2 in the pathogenesis of BPD and neonatal lung injury. Firstly, a hyperoxia-induced mouse model with BPD was established. LncRNAs with differential expression in lung tissues of normal and BPD mice were analyzed by microarray. An adenovirus vector overexpressing CASC2 was constructed and its functions on BPD symptoms in model mice were analyzed. Gain- and loss-of function studies of CASC2 were performed in a bronchial epithelial cell line BEAS-2B to determine its role in cell apoptosis and proliferation under normoxic and hyperoxic conditions. The downstream mechanical molecules of lncRNA CASC2 were predicted on bioinformatics systems and confirmed by luciferase assays. The functional interactions among lncRNA CASC2, miR-194-5p, and CAV1 in BPD were determined by rescue experiments. Consequently, lncRNA CASC2 was found to be poorly expressed in BPD mice. Besides, overexpressed CASC2 was found to relieve the symptoms of BPD in neonatal mice and suppress apoptosis as well as promote proliferation in hyperoxia-induced BEAS-2B cells. Importantly, CASC2 was found to regulate CAV1 expression by competitively binding to miR-194-5p and downregulate the activity of the TGF-ß1 signaling pathway, thereby suppressing lung injury. Either miR-194-5p upregulation or CAV1 downregulation blocked the roles of CASC2. To sum up, this study evidenced that CASC2 alleviates hyperoxia-induced lung injury in mouse and cell models with the involvement of a miR-194-5p-CAV1 crosstalk and the TGF-ß1 inactivation.
Assuntos
Caveolina 1/antagonistas & inibidores , Hiperóxia/fisiopatologia , Lesão Pulmonar/prevenção & controle , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Animais , Animais Recém-Nascidos , Apoptose , Caveolina 1/genética , Caveolina 1/metabolismo , Proliferação de Células , Feminino , Regulação da Expressão Gênica , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , MicroRNAs/genética , Transdução de SinaisRESUMO
Co-composting with exogenous microbial inoculant, presents an effective approach for the harmless utilization of livestock manure and agroforestry wastes. However, the impact of inoculant application on the variations of viral and antibiotic resistance genes (ARGs) remains poorly understood, particularly under varying manure quantity (low 10 % vs. high 20 % w/w). Thus, employing virome and metagenomic sequencing, we examined the influence of Streptomyces-Bacillus Inoculants (SBI) on viral communities, phytopathogen, ARGs, mobile genetic elements, and their interrelations. Our results indicate that SBI shifted dominant bacterial species from Phenylobacterium to thermotropic Bordetella, and the quantity of manure mediates the effect of SBI on whole bacterial community. Major ARGs and genetic elements experienced substantial changes with SBI addition. There was a higher ARGs elimination rate in the composts with low (â¼76 %) than those with high manure (â¼70 %) application. Virus emerged as a critical factor influencing ARG dynamics. We observed a significant variation in virus community, transitioning from Gemycircularvirus- (â¼95 %) to Chlamydiamicrovirus-dominance. RDA analysis revealed that Gemycircularvirus was the most influential taxon in shaping ARGs, with its abundance decreased approximately 80 % after composting. Collectively, these findings underscore the role of microbial inoculants in modulating virus communities and ARGs during biowaste co-composting.
Assuntos
Compostagem , Resistência Microbiana a Medicamentos , Esterco , Metagenômica , Streptomyces , Esterco/microbiologia , Esterco/virologia , Streptomyces/genética , Resistência Microbiana a Medicamentos/genética , Viroma/genética , Bactérias/efeitos dos fármacos , Bactérias/genética , Vírus/efeitos dos fármacos , Vírus/genética , Microbiologia do Solo , Antibacterianos/farmacologia , MetagenomaRESUMO
This study aimed to enhance the use of male sterility in pepper to select superior hybrid generations. Transcriptomic and proteomic analyses of fertile line 1933A and nucleic male sterility line 1933B of Capsicum annuum L. were performed to identify male sterility-related proteins and genes. The phylogenetic tree, physical and chemical characteristics, gene structure characteristics, collinearity and expression characteristics of candidate genes were analyzed. The study identified 2,357 differentially expressed genes, of which 1,145 and 229 were enriched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, respectively. A total of 7,628 quantifiable proteins were identified and 29 important proteins and genes were identified. It is worth noting that the existence of CaPRX genes has been found in both proteomics and transcriptomics, and 3 CaPRX genes have been identified through association analysis. A total of 66 CaPRX genes have been identified at the genome level, which are divided into 13 subfamilies, all containing typical CaPRX gene conformal domains. It is unevenly distributed across 12 chromosomes (including the virtual chromosome Chr00). Salt stress and co-expression analysis show that male sterility genes are expressed to varying degrees, and multiple transcription factors are co-expressed with CaPRXs, suggesting that they are involved in the induction of pepper salt stress. The study findings provide a theoretical foundation for genetic breeding by identifying genes, metabolic pathways, and molecular mechanisms involved in male sterility in pepper.
RESUMO
Introduction: Female empowerment can promote gender equality and realize women's comprehensive development, while the Internet has opened up an effective channel for female empowerment. Methods: Given the relative lack of women's rights in rural China and the rapid Internet development, this paper, based on the 2021 China Comprehensive Social Survey data, first analyses the effect of Internet embeddedness on rural women's non-farm employment using the Probit model. Then, it uses the mediation effect model to explore the role of women's rights perception in the mechanism between Internet embeddedness and women's non-farm employment. Finally, based on age and regional differences, we also analyze the impact of Internet embeddedness on female non-farm employment. Results: The paper draws the following conclusions: (1) Internet embedding can promote female non-farm employment, and the probability of female non-farm employment is 3.71% for each degree of Internet embedding. (2) Internet embedding can enhance women's perception of their rights and thus promote women's non-farm employment. (3) Internet embedding can enhance the perception of rights of young rural women, which can promote their nonfarm employment. However, the influence of internet embedding on middle-aged women's perception of rights is not significant. (4) Internet embedding in the eastern region can enhance women's perception of rights and realize women's non-farm employment; on the contrary, in the central and western regions, Internet embedding cannot enhance rural women's perception of rights. Discussion: Therefore, this paper proposes to release further the impact of the Internet in promoting rural women's non-farm employment to improve the deprivation of rural women's rights and promote gender equality and women's comprehensive development.
RESUMO
Wetlands are facing gradual drying, leading to large carbon loss due to the transformation from anaerobic to aerobic conditions, but the temperature and drought effects from the temperature and moisture fluctuation on soil organic carbon (SOC) mineralization remain uncertain. An incubation study with three moisture levels (100%, 60%, and 40% WHC, marked as W100, W60, and W40, respectively) and four temperature levels (5, 10, 15, 20 °C, marked as T5, T10, T15, and T20, respectively) was conducted to determine the effect of temperature and moisture interactions on SOC mineralization in the karst wetland of the Yunnan-Guizhou Plateau. Compared with T5, the cumulative mineralization CO2 in T20 increased by 83.18% (W40), 154.63% (W60), and 148.16% (W100), respectively. The mineralized CO2 at W60 and W40 significantly decreased compared to that at W100 at the four temperature levels. Temperature, moisture and their interactions had significant positive effects on SOC mineralization rates and cumulative mineralized CO2. The temperature sensitivity of SOC mineralization rates (Q10) under W40 and W60 increased by 22.03% and 24.52%, respectively, compared to that under W100. The cumulative mineralized CO2 was positively related to soil urease activity and negatively related to soil pH, N-NH4+, SOM, and catalase activity. Temperature and moisture fluctuation and soil properties explained 85.40% of the variation in SOC mineralization, among which temperature and moisture fluctuation, soil properties, and their interactions explained 19.71%, 4.81%, and 60.88%, respectively. Our results indicated that SOC mineralization is influenced by the joint effect of temperature and drought, as well as their induced changes in soil properties, in which higher temperatures can increase soil CO2 emissions by enhancing the SOC mineralization rate, but the positive effect may be weakened from the drying wetland.
Assuntos
Carbono , Solo , Carbono/análise , Solo/química , Áreas Alagadas , Temperatura , Dióxido de Carbono , ChinaRESUMO
Latent autoimmune diabetes in adults (LADA) is a heterogeneous subtype of diabetes characterized by islet cell destruction mediated by islet autoimmunity and insulin resistance. Metabolic syndrome (MetS) is a state in which many risk factors for metabolic and cardiovascular diseases accumulate in an individual. Based on clinical data, this review covers the prevalence of MetS in LADA, focusing on the risk associated with and the role of insulin resistance in the development of LADA from the perspective of inflammatory factors, environmental factors, and the gut microbiota, aiming to improve our understanding of this condition.
Assuntos
Diabetes Mellitus Tipo 1 , Intolerância à Glucose , Resistência à Insulina , Diabetes Autoimune Latente em Adultos , Síndrome Metabólica , Autoanticorpos , Humanos , Síndrome Metabólica/epidemiologiaRESUMO
The complete mitogenome of Polyozellus multiplex (Underw.) Murrill 1910, was first sequenced, assembled, and annotated in the present study. The mitogenome length was 47,054 bp with a GC content of 23.35%, including 14 conserved protein-coding genes, one ribosomal protein (RPS3), two DNA polymerases (DPO), two rRNA genes (RNS and RNL), and 24 transfer RNA (tRNA) genes. Phylogenetic analysis, based on a combined mitochondrial gene dataset from 17 taxa of four orders within the class Agaricomycetes, was conducted using maximum-likelihood (ML) and Bayesian inference (BI) methods. It is revealed that P. multiplex is closely related to Thelephora aurantiotincta Corner 1968, both of them have been clustered into Thelephorales.
RESUMO
Many plants adapted to harsh environments have evolved low seed mass ('light seeds') with specific dispersal strategies, primarily either by wind (anemochory) or water (hydrochory). However, the role of their seed microbiota in their survival, and their seed microbial abundance and structure, remain insufficiently studied. Herein, we studied the light seed microbiome of eight anemochores and two hydrochores (as controls) collected from four provinces in China, using qPCR and metagenomic sequencing targeting both bacteria and fungi. Substantial variations were found for seed endophytic fungi (9.9 × 1010~7.3 × 102 gene copy numbers per seed) and bacteria (1.7 × 1010~8.0 × 106). Seed microbial diversity and structure were mainly driven by the plant genotype (species), with weak influences from their host plant classification level or dispersal mode. Seed microbial composition differences were clear at the microbial phylum level, with dominant proportions (~75%) for Proteobacteria and Ascomycota. The light seeds studied harbored unique microbial signatures, sharing only two Halomonas amplicon sequence variants (ASVs) and two fungal ASVs affiliated to Alternaria and Cladosporium. A genome-level functional profile analysis revealed that seed bacterial microbiota were enriched in amino acid, nucleoside, and nucleotide biosynthesis, while in fungal communities the generation of precursor metabolites and respiration were more highly represented. Together, these novel insights provide a deeper understanding of highly diversified plant-specific light seed microbiota and ecological strategies for plants in harsh environments.
RESUMO
Ovate family proteins (OFPs) are transcriptional inhibitors that regulate plant growth and development and play important roles in the synthesis of secondary cell walls during pollen development. This study identified the pepper OFP gene family based on the genome-wide analysis and used bioinformatics methods to provide a fundamental profile of the gene family. 74 OFP genes with typical Ovate domain were identified in cultivated pepper Zunla-1, wild pepper Chiltepin and CM334. Chromosome mapping revealed that CazOFP genes were unevenly distributed on 11 chromosomes and Chr00 in Zunla-1, CacOFP genes on 12 chromosomes in Chiltepin, and CamOFP genes on 12 chromosomes and two Scaffflods in CM334. Gene structure analysis revealed that CaOFP genes possessed 1-3 exons, and the analysis of physicochemical properties suggested that CaOFPs were hydrophilic. Many cis-acting elements were identified in the promoter region of CaOFP genes, including ABRE, ARE, Box 4, G-box, TC-rich, and TCT-motif. The expression patterns of pepper at different growth stages showed that CaOFP genes were actively involved in the growth and fruit development of pepper, and CazOFP16 and CazOFP17 were actively involved in response to multiple hormones and stress events. qRT-PCR was also used to verify the expression of CazOFP gene in two developmental stages of seven pepper varieties with different fruit shapes, and it was found that CaOFP genes may be involved in the formation of fruit type in pepper. This study provides theoretical and practical evidence for future research on the OFP gene family.
RESUMO
To investigate the Th1/Th2 cytokine profile in patients with lymphoma during the myelosuppression stage of infection. 52 patients with gram-negative bacterial infection (G- group), 49 patients with gram-positive bacterial infection (G+ group), 51 uninfected patients with lymphoma (uninfected group) and 20 healthy controls (healthy group) were enrolled in this study. We evaluated the quantification of Th1/Th2 cytokines with flow cytometry bead assay (CBA) in the sera to explore a rapid diagnostic method to determine the type of infection and anti-infective effect. The levels of procalcitonin (PCT) were also detected simultaneously. The four groups did not differ with regard to IL-2 and IL-4 (P>0.05). The IFN-γ and TNF-α levels of patients with lymphoma were higher than those of healthy controls (P<0.05). There was significantly upregulated IL-6 and IL-10 expression in the G- group (P<0.001). A similar trend was reflected in the IL-6 of the G+ group, which was significantly increased (P<0.001). However, no significant upregulation was observed for IL-10 in the G+ group. According to the different degrees of increased IL-6 and IL-10 levels, We proposed to use the G- Bacterial Infection Cytokine Profile (G- BICP) and the G+ Bacterial Infection Cytokine Profile (G+ BICP) for the first time to differentiate between Gram-negative and Gram-positive (G-/G+) bacterial infection in adults with lymphoma in the myelosuppression stage after chemotherapy. The IL-6, IL-10 and PCT in the G- group and the IL-6, PCT in the G+ group were significantly decreased at day 4 and day 8 compared with those at day 1. IL-6 and IL-10 are closely associated with the severity and treatment efficacy in adults with lymphomas who develop infections after chemotherapy and can help distinguish between G- and G+ bacterial infections at an early stage.
Assuntos
Infecções por Bactérias Gram-Positivas , Linfoma , Adulto , Citocinas , Bactérias Gram-Positivas , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Interleucina-10 , Interleucina-6 , Linfoma/tratamento farmacológico , Pró-CalcitoninaRESUMO
The Na+/H+ exchangers (NHXs) are a class of transporters involved in ion balance during plant growth and abiotic stress. We performed systematic bioinformatic identification and expression-characteristic analysis of CaNHX genes in pepper to provide a theoretical basis for pepper breeding and practical production. At the whole-genome level, the members of the CaNHX gene family of cultivated and wild pepper were systematically identified using bioinformatics methods. Sequence alignment and phylogenetic tree construction were performed using MEGA X software, and the gene functional domain, conserved motif, and gene structure were analyzed and visualized. At the same time, the co-expression network of CaNHX genes was analyzed, and salt-stress analysis and fluorescence quantitative verification of the Zunla-1 cultivar under stress conditions were performed. A total of 9 CaNHX genes were identified, which have typical functional domains of the Na+/H+ exchanger gene. The physical and chemical properties of the protein showed that the protein was hydrophilic, with a size of 503-1146 amino acids. Analysis of the gene structure showed that Chr08 was the most localized chromosome, with 8-24 exons. Cis-acting element analysis showed that it mainly contains cis-acting elements such as light response, salicylic acid response, defense, and stress response. Transcriptom and co-expression network analysis showed that under stress, the co-expressed genes of CaNHX genes in roots and leaves were more obvious than those in the control group, including ABA, IAA, and salt. The transcriptome and co-expression were verified by qRT-PCR. In this study, the CaNHX genes were identified at the genome level of pepper, which provides a theoretical foundation for improving the stress resistance, production, development, and utilization of pepper in genetic breeding.
RESUMO
This real-world, observational study aimed to assess and compare the clinical efficacy and safety of eltrombopag with recombinant human thrombopoietin (rhTPO) in the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma. One hundred and fifty-three patients who experienced grade 3 or 4 thrombocytopenia after chemotherapy for lymphoma were enrolled, 51 of which were treated with eltrombopag, 50 with rhTPO, and 52 patients with no drug treatment were served as the control group. The lowest platelet level and mean platelet counts at Day 5, Day 7, and Day 10 were significantly higher in both the eltrombopag group (P=.041,.003,.000,.000) and rhTPO group (P=.005,.005,.000,.000) than the control, but there was no difference between treatment with eltrombopag and rhTPO. Similarly, days required for the recovery of platelet counts to ≥50×109/L and ≥75×109/L were not different between the two treatment groups but significantly higher than the control group (P <.05). Rates of bleeding and platelet transfusion were all significantly reduced in patients treated with eltrombopag (P=.031,.032) or rhTPO (P=.017,.009) when compared to the control. Treatment-related adverse events (AEs) were reported in 7 (13.7%) and 6 (12.0%) patients in the eltrombopag and rhTPO groups, respectively, all being mild and transient in nature. In conclusion, both eltrombopag and rhTPO were effective and safe in the treatment of thrombocytopenia after chemotherapy for lymphoma.
RESUMO
PURPOSE: Case reports suggest that ruxolitinib-containing treatment could increase the clinical response rate of patients with hemophagocytic syndrome (HPS). This study aimed to explore the effect of ruxolitinib-containing treatment for patients with lymphoma-associated hemophagocytic syndrome (LAHS). METHODS: This was a retrospective study of patients with LAHS hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University between October 2017 and September 2019. Patients were treated with HLH-94 (etoposide and dexamethasone) or R-DED regimen (ruxolitinib, doxorubicin, etoposide, and dexamethasone). The clinical characteristics, treatment responses, and overall survival (OS) were compared. The patients were divided into the HLH-94 group (n = 34) and the R-DED group (n = 36). RESULTS: Compared with HLH-94, R-DED might effectively improve the clinical manifestations, including fever and splenomegaly in patients with LAHS, and control the systemic cytokine storm. The response rate at 2 weeks was 54.8% in the HLH-94 group, which was lower than in the R-DED group (83.3%) (p = 0.011). The OS was significantly prolonged in the R-DED group compared with the HLH-94 group (median, 5 vs. 1.5 months, p = 0.003). The multivariable analysis showed that lower IL-10 levels [hazard ratio (HR)] = 1.000, [95% confidence interval (CI)] 1.000-1.000, p = 0.012), R-DED regimen (HR = 0.196, 95% CI 0.084-0.457, p < 0.001), and non-NK/T-cell lymphoma (HR = 0.254, 95% CI 0.102-0.628, p = 0.003) were associated with better OS. The prognosis of patients with LAHS was generally poor. CONCLUSION: Ruxolitinib can be combined with chemotherapy in HPS. It is feasible, with no early signals of increased toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma/complicações , Linfoma/tratamento farmacológico , Adulto , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirazóis/administração & dosagem , Pirimidinas , Estudos RetrospectivosRESUMO
BACKGROUND: Aromatic rice is popular worldwide because of its characteristic fragrance. Genetic studies and physical fine mapping reveal that a candidate gene (fgr/OsBADH2) homologous to betaine aldehyde dehydrogenase is responsible for aroma metabolism in fragrant rice varieties, but the direct evidence demonstrating the functions of OsBADH2 is lacking. To elucidate the physiological roles of OsBADH2, sequencing approach and RNA interference (RNAi) technique were employed to analyze allelic variation and functions of OsBADH2 gene in aroma production. Semi-quantitative, real-time reverse transcription-polymerase chain reaction (RT-PCR), as well as gas chromatography-mass spectrometry (GC-MS) were conducted to determine the expression levels of OsBADH2 and the fragrant compound in wild type and transgenic OsBADH2-RNAi repression lines, respectively. RESULTS: The results showed that multiple mutations identical to fgr allele occur in the 13 fragrant rice accessions across China; OsBADH2 is expressed constitutively, with less expression abundance in mature roots; the disrupted OsBADH2 by RNA interference leads to significantly increased 2-acetyl-1-pyrroline production. CONCLUSION: We have found that the altered expression levels of OsBADH2 gene influence aroma accumulation, and the prevalent aromatic allele probably has a single evolutionary origin.
Assuntos
Regulação para Baixo/genética , Regulação da Expressão Gênica de Plantas , Odorantes , Oryza/genética , Proteínas de Plantas/genética , Pirróis/metabolismo , Interferência de RNA , Alelos , China , Segregação de Cromossomos , Produtos Agrícolas/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Germinação , Nucleotídeos/genética , Oryza/anatomia & histologia , Oryza/crescimento & desenvolvimento , Fenótipo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plântula/crescimento & desenvolvimentoRESUMO
Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA ≥ 1000 copies/ml before switch, the proportion of viral load (VL) ≥ 1000 copies/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA < 1000 copies/ml before switch, the proportion of VL ≥ 1000 copies/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3%, and 1.1% before regimen switch to 26.8%, 18.3%, and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA ≥ 1000 copies/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , RNA Viral/antagonistas & inibidores , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , China , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/crescimento & desenvolvimento , Humanos , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , RNA Viral/genética , Ritonavir/uso terapêutico , População Rural , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
OBJECTIVE: To understand the one-year effect of HCV/HIV co-infected patients who had received AIDS second-line antiretroviral treatment after failure virologically, on the first-line therapy. METHODS: HCV and HIV antibody positive patients who had experienced virological failure but received at least one-year AIDS first-line treatment, were recruited from May to October 2012 in Xincai, Queshan and Weishi of Henan province. 6-months and 12-months follow-up programs were carried out after the regimen had been changed to AIDS second-line antiretroviral treatment, CD4⺠T lymphocyte count, HIV-1 virus load and HIV-1 drug resistance were performed. RESULTS: Eighty-one cases of eligible patients were selected and followed by an amelioration of CD4 median at 6-month and 12-month follow-up period. Data showed that the baseline, 6-months and 12-months CD4 medians were 266 cells/µl, 275 cells/µl and 299 cells/µl (χ² = 8.214, P = 0.009). The ratio of HIV virus load suppression patients at 6-months and 12-months follow-up increased to 46.84% and 50.00%, respectively. Frequencies of HIV drug resistance also decreased at the baseline, 6-months and 12-months, with ratios as 66.67%, 26.58% and 27.63% (χ² = 29.362, P = 0.000), respectively. Ratios of patients that holding NRTI and NNRTI drug resistance appeared coinstantaneous decrease at the baseline, 6-months and 12-months, as 51.85%, 18.99% and 17.11% (χ² = 14.230, P = 0.005). At the baseline, the ratios of patients resisted to 3TC, ABC and FTC were all more than 50%, with AZT, D4T and DDI between 41%-44% while TDF appeared as 33.33%, then all of them declined to 12%-18% at the 6-month and 12-month follow-up periods. 65.43% of the patients resisted to both NVP and EFV but declined to 24%-27% at 6 months and 12 months. CONCLUSION: HCV/HIV co-infected patients experienced virological failure of AIDS first-line therapy were ameliorated after changing to use second-line antiretroviral treatment for 6-months, but did not show constant positive effect at the 12-month end point.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Fármacos Anti-HIV/farmacologia , Linfócitos T CD4-Positivos , China , Coinfecção , Seguimentos , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China. DESIGN: We recruited 365 patients on cART in two rural Chinese counties in 2003-2004 and followed them every 6 months until May 2010. METHODS: Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan-Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality. RESULTS: At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (≈ 18-month median interval between each adverse milestone). Being male, having a baseline CD4 cell count of less than 50 cells/µl and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01-3.48). CONCLUSION: HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early.
Assuntos
Antirretrovirais/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Adulto , Antirretrovirais/farmacologia , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , China , Estudos de Coortes , Feminino , HIV/isolamento & purificação , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Falha de Tratamento , Carga ViralRESUMO
This study was aimed to investigate the expressions of multiple cytokines on bone marrow mesenchymal stem cells (MSC) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), and its significance. The semi-quantitative reverse transcriptase-PCR (RT-PCR) was used to detect the expressions of IL-1ß, SCF, G-CSF at mRNA level in bone marrow MSC of patients with AA and MDS. The real time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the mRNA expression of TPO in bone marrow MSC of AA and MDS patients. The results indicated that the expression of SCF in AA group was much lower than that in the normal control group (p < 0.05), and the expression of TPO in AA group was higher than that in the normal control group (p < 0.05), while the expression of IL-1ß of AA had no significant difference when compared with the normal control group (p > 0.05). Compared with normal control group, the expressions of SCF of MDS patients was lower (p < 0.05), but the expressions of IL-1ß and TPO did not show significant difference (p > 0.05). The expressions of IL-1ß, SCF and TPO were no significant difference between AA and MDS groups (p > 0.05). Neither the AA patients, MDS patients nor the normal control group had the expression of G-CSF. It is concluded that the expression of SCF and TPO in bone marrow MSC of AA patients are obviously abnormal, the expression of SCF is also abnormal in bone marrow MSC of MDS patients.