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1.
BMC Microbiol ; 21(1): 267, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607556

RESUMO

BACKGROUND: Tuberculosis (TB) is a serious chronic infectious disease caused by Mycobacterium tuberculosis complex (MTBC). Hence, the development of a novel, simple, rapid and sensitive method to detect MTBC is of great significance for the prevention and treatment of TB. RESULTS: In this study, multiple cross displacement amplification (MCDA) combined with a nanoparticle-based lateral flow biosensor (LFB) was developed to simultaneously detect two target genes (IS6110 and mpb64) of MTBC (MCDA-LFB). One suite of specific MCDA primers designed for the IS6110 and mpb64 genes was validated using genomic DNA extracted from the reference strain H37Rv. The MCDA amplicons were analyzed using a real-time turbidimeter, colorimetric indicator (malachite green, MG) and LFBs. The optimal amplification temperature and time were confirmed, and the MCDA-LFB method established in the current report was evaluated by detecting various pathogens (i.e., reference strains, isolates and clinical sputum samples). The results showed that the two sets of MCDA primers targeting the IS6110 and mpb64 genes could effectively detect MTBC strains. The optimal reaction conditions for the MCDA assay were determined to be 67 °C for 35 min. The MCDA assay limit of detection (LoD) was 100 fg per reaction for pure genomic DNA. The specificity of the MCDA-LFB assay was 100%, and there were no cross-reactions for non-MTBC strains. For sputum samples and MTBC strain detection, the positive rate of MCDA-LFB for the detection of MTBC strains was consistent with seminested automatic real-time PCR (Xpert MTB/RIF) and higher than acid-fast staining (AFS) and culture assays when used for sputum samples. The MCDA-LFB assay was a rapid tool, and the whole procedure for MCDA-LFB, including DNA template preparation, MCDA reaction and amplification product analysis, was completed within 70 min. CONCLUSION: The MCDA-LFB assay targeting the IS6110 and mpb64 genes is a simple, rapid, sensitive and reliable detection method, and it has potential significance for the prevention and treatment of TB.

2.
Tuberculosis (Edinb) ; 131: 102123, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34555658

RESUMO

BACKGROUND: Macrophages play an important role in the host immune response against mycobacterial infection, and this process is regulated by various factors, including circular RNAs (circRNAs). We intended to explore the role of circ_0001490 in tuberculosis (TB) using Mycobacterium tuberculosis (M.tb)-infected THP-1 macrophages. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to measure RNA and protein expression, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to analyze the viability of THP-1 macrophages. Flow cytometry was performed to analyze the apoptosis rate of THP-1 macrophages. Enzyme-linked immunosorbent assay (ELISA) was conducted to assess the release of inflammatory cytokines. Colony-forming unit (CFU) assay was conducted to analyze the survival of M.tb in THP-1 macrophages. Intermolecular target interaction was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0001490 expression was down-regulated in the serum samples of TB patients and M.tb-infected THP-1 macrophages. Circ_0001490 overexpression suppressed M.tb survival and promoted the viability and inflammatory response of THP-1 macrophages. Circ_0001490 interacted with microRNA-579-3p (miR-579-3p), and circ_0001490 overexpression-induced protective effects in M.tb-infected THP-1 macrophages were largely overturned by the overexpression of miR-579-3p. miR-579-3p interacted with the 3' untranslated region (3'UTR) of follistatin-like protein 1 (FSTL1). FSTL1 silencing largely overturned miR-579-3p knockdown-induced effects in M.tb-infected THP-1 macrophages. Circ_0001490 acted as miR-579-3p sponge to up-regulate FSTL1 in THP-1 macrophages. CONCLUSION: In conclusion, our results demonstrated that circ_0001490 suppressed M.tb survival and promoted the viability and inflammatory response of M.tb-infected THP-1 macrophages partly by regulating miR-579-3p/FSTL1 axis.

3.
Medicine (Baltimore) ; 100(35): e27187, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477178

RESUMO

ABSTRACT: It is well-known that microRNAs are able to regulate the expression of target mRNAs through complementary base-pairing to their 3'-untranslated regions (3'UTR) sequences. This study aimed to investigate whether single nucleotide polymorphisms resided in the 3'UTR sequences in patients with chronic hepatitis B viruses (HBV) infection are associated with the development and metastasis of hepatocellular carcinoma (HCC). Seventeen single nucleotide polymorphisms in the 3'UTR sequence of 10 genes regulated or affected by hepatitis B virus X protein were found by bioinformatics methods. Two hundred fifteen patients with HBV-related HCC and 216 patients with chronic HBV infection were recruited. Through case-control study, only found that the von Hippel-Lindau gene rs1642742 (G>A) may be associated with the occurrence and metastasis of HCC. The ORs of the frequencies of rs1642742 A allele versus G allele were 1.424 (P = .038, 95% confidence interval [CI] = 1.019-1.989) between HBV-related HCC and chronic HBV infection group and were 2.004 (P = .037, 95%CI = 1.031-3.895) between tumor metastasis and non-metastasis group, respectively. Through multivariate regression analysis, we also found that rs1642742 AA genotype was an independent risk factor for tumor metastasis (odds ratio = 2.227, 95% CI = 1.043-4.752, P = .038) in HBV-related HCC group. Our study suggested that Von Hippel-Lindau rs1642742 contributed to susceptibility to developing HCC and correlated with tumor metastasis.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B Crônica/complicações , Neoplasias Hepáticas/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Polimorfismo de Nucleotídeo Único
4.
J Control Release ; 339: 1-13, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34536449

RESUMO

Cell-based therapies could overcome the limitations of traditional drugs for the treatment of refractory diseases. Cell exchange between the bone marrow and blood is bidirectional. Several kinds of cells in the blood have the capability to enter the bone marrow by interacting with sinusoidal cells under specific physiological or pathological conditions. These cells are the potential living therapeutics or delivery vehicles to treat or prevent bone marrow-related hematologic diseases. In this review, we summarized the in vivo molecular mechanisms and kinetics of these cells in entering the bone marrow. The advances in the fabrication of living cell drugs and the strategies to design cell-based carriers into the bone marrow were discussed. The latest studies on how to use blood cells as living drugs or as drug carriers to improve therapeutic outcomes of hematologic diseases inside the bone marrow were highlighted.

5.
Arch Pharm Res ; 44(7): 633-654, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269984

RESUMO

Atractylodes macrocephala Koidz is a widely used as a traditional Chinese medicine. Atractylenolides (-I, -II, and -III) are a class of lactone compounds derived from Atractylodes macrocephala Koidz. Research into atractylenolides over the past two decades has shown that atractylenolides have anti-cancer, anti-inflammatory, anti-platelet, anti-osteoporosis, and antibacterial activity; protect the nervous system; and regulate blood glucose and lipids. Because of structural differences, both atractylenolide-I and atractylenolide-II have remarkable anti-cancer activities, and atractylenolide-I and atractylenolide-III have remarkable anti-inflammatory and neuroprotective activities. We therefore recommend further clinical research on the anti-cancer, anti-inflammatory and neuroprotective effects of atractylenolides, determine their therapeutic effects, alone or in combination. To investigate their ability to regulate blood glucose and lipid, as well as their anti-platelet, anti-osteoporosis, and antibacterial activities, both in vitro and in vivo studies are necessary. Atractylenolides are rapidly absorbed but slowly metabolized; thus, solubilization studies may not be necessary. However, due to the inhibitory effects of atractylenolides on metabolic enzymes, it is necessary to pay attention to the possible side effects of combining atractylenolides with other drugs, in clinical application. In short, atractylenolides have considerable medicinal value and warrant further study.

6.
Brain Res Bull ; 174: 281-295, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216649

RESUMO

Rehmannia glutinosa, the fresh or dried root of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & Mey., and Gardenia, the fruit of Gardenia jasminoides Ellis from Rubiaceae, both are famous traditional Chinese medicines that have been traditionally used in China. Catalpol and geniposide, as two kinds of iridoid glycosides with high activities, are the main bioactive components in Rehmannia glutinosa and Gardenia jasminoides Ellis, respectively. Over the past few decades, catalpol and geniposide have been widely studied for their therapeutic effects. The preclinical experiments demonstrated that they possessed significant neuroprotective activities against Alzheimer's disease, Parkinson's disease, stroke, and depression, etc. In this paper, the pharmacological effects and mechanisms of catalpol and geniposide on Alzheimer's disease and Parkinson's disease from 2005 to now were systematically summarized and comprehensively analyzed. At the same time, the pharmacokinetic characteristics of the analyzed compounds were also described, hoping to provide some enlightenment for the design, research, and development of iridoid glycosides.

7.
Braz J Microbiol ; 52(3): 1315-1325, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34176103

RESUMO

Tuberculosis (TB) is the deadliest infectious caused by Mycobacterium tuberculosis complex (MTBC). Because most TB cases occur within low-income populations, developing a specific, sensitive, cost-saving, and rapid point-of-care test for the early diagnosis of TB is important for achieving the WHO's End Tuberculosis Strategy. In the current study, a novel nucleic acid detection strategy that includes multiplex loop-mediated isothermal amplification combined with a nanoparticle-based lateral flow biosensor (mLAMP-LFB) was used to detect MTBC. The two sets of LAMP primers specific to the IS6110 and gyrB genes of MTBC were successfully designed and validated for the detection of MTBC. The preferred reaction conditions for this assay were confirmed to be 65 °C for 40 min, and the amplification products could be visually identified through LFB within 2 min. The full assay process, including genomic DNA template extraction, LAMP reaction, and product detection, could be completed in 80 min. The limit detection of the assay was 100 fg of DNA in pure culture. The specificity of the assay was 100%, and it had no cross-reactions to other strains. Thus, the m-LAMP-LFB technology established in the present study was an objective, rapid, simple, and sensitive assay for MTBC identification, which could be applied in a clinical setting, especially in resource-constrained regions of the world.

8.
Anal Chem ; 93(7): 3378-3385, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33560116

RESUMO

Thienoisoindigo as a popular conjugated skeleton has been constantly applied in the construction of organic optoelectronic materials. Exploring its new applications in fluorescent sensors and bioimaging is helpful to extend its potential. In this work, a thienoisoindigo fluorophore was first selected as a building block to be applied in the construction of the near-infrared fluorescent materials with an aggregation-induced emission manner through introducing triarylamine, thiophene-bridged triarylamine, and N,N-dimethyl styrene, respectively. These fluorescent agents showed the near-infrared emission and possessed typical aggregation-induced emission behavior. Although they had low band gaps and near-infrared emission, they presented remarkable photostability. Especially, thiophene-bridged triarylamine and N,N-dimethyl styrene-coated thienoisoindigos exhibited strong lysosomal targeting capability, and they could also serve for fluorescence imaging in vivo.


Assuntos
Diagnóstico por Imagem , Corantes Fluorescentes , Imagem Óptica
9.
J Cell Physiol ; 236(2): 1158-1183, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32710499

RESUMO

The pathogenic mechanisms of Helicobacter pylori infection remain to be defined, and potential interventional microbiota are just beginning to be identified. In this study, gene-set enrichment analysis (GSEA) was used to integrate three H. pylori infection microarray data sets from the gene expression omnibus database and identified ten hallmark gene sets and 35 Kyoto encyclopedia of genes and genomes (KEGG) pathways that differed between healthy and Helicobacter pylori-infected individuals. Weighted gene co-expression network analysis (WGCNA) performed on two of the data sets identified three key gene coexpression modules. These modules contained 54 enriched KEGG pathways, 25 of which overlapped with the GSEA analysis, suggesting potentially important roles in H. pylori-infection. We selected 116 hub genes from the three key modules for in vitro validation at the transcriptional level using H. pylori Sydney Strain 1 and verified the upregulation of 80. WGCNA of the microbiomes based on 20 mucosal samples and a sequence read archive data set revealed four microbiota modules correlated with H. pylori infection. The negatively correlated modules contained 11 microbiome families. These findings provide new insight into the pathogenesis of H. pylori infection and systematically identify 25 key pathways, 80 upregulated hub genes, and 11 families of candidate interventional microbiota for further research.


Assuntos
Redes Reguladoras de Genes/genética , Predisposição Genética para Doença , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Adulto , Idoso , Biologia Computacional , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Ontologia Genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Análise em Microsséries , Microbiota/genética , Pessoa de Meia-Idade , Transdução de Sinais/genética
10.
Expert Rev Anti Infect Ther ; 19(7): 911-925, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33346681

RESUMO

Introduction: Calycosin (CA), a typical phytoestrogen extracted from root of Astragalus membranaceus. On the basis of summarizing the pharmacological and pharmacokinetic studies of CA in recent years, we hope to provide useful information for CA about treating different diseases and to make suggestions for future research.Areas covered: We collected relevant information (January 2014 to March 2020) on CA via the Internet database. Keywords searched includ pharmacology, pharmacokinetics and toxicology, and the number of effective references was 118. CA is a phytoestrogen with wide range of pharmacological activities. By affecting PI3K/Akt/mTOR, WDR7-7-GPR30, Rab27B-ß-catenin-VEGF, etc. signaling pathway, CA showed the effect of anticancer, anti-inflammatory, anti-osteoporosis, neuroprotection, hepatoprotection, etc. Therefore, CA is prospective to be used in the treatment of many diseases.Expert opinion: Research shows that CA has a therapeutic effect on a variety of diseases. We think CA is a promising natural medicine. Therefore, we propose that the research directions of CA in the future include the following. Carrying out clinical research trials in order to find the most suitable medicinal concentration for different diseases; Exploring the synergistic mechanism of CA in combination with other drugs; Exploring ways to increase the blood circulation concentration of CA.


Assuntos
Medicamentos de Ervas Chinesas/química , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Animais , Humanos , Isoflavonas/efeitos adversos , Isoflavonas/isolamento & purificação , Fitoestrógenos/efeitos adversos , Fitoestrógenos/isolamento & purificação
11.
Pharmacol Res ; 164: 105373, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33316380

RESUMO

Lupeol is a natural triterpenoid that widely exists in edible fruits and vegetables, and medicinal plants. In the last decade, a plethora of studies on the pharmacological activities of lupeol have been conducted and have demonstrated that lupeol possesses an extensive range of pharmacological activities such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. Pharmacokinetic studies have indicated that absorption of lupeol by animals was rapid despite its nonpolar characteristics, and lupeol belongs to class II BCS (biopharmaceutics classification system) compounds. Moreover, the bioactivities of some isolated or synthesized lupeol derivatives have been investigated, and these results showed that, with modification to C-3 or C-19, some derivatives exhibit stronger activities, e.g., antiprotozoal or anticancer activity. This review aims to summarize the advances in pharmacological and pharmacokinetic studies of lupeol in the last decade with an emphasis on its anticancer and anti-inflammatory activities, as well as the research progress of lupeol derivatives thus far, to provide researchers with the latest information, point out the limitations of relevant research at the current stage and the aspects that should be strengthened in future research.

12.
Cancer Biol Ther ; 21(11): 1005-1013, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33054568

RESUMO

BACKGROUND: There is an unmet need to identify novel mechanism-based prognostic genes associated with hepatocellular carcinoma (HCC) recurrence that can predict patient outcomes and provide therapeutic targets. This study aims to identify potential novel driver genes and mutations in HCC. METHODS: Single nucleotide variations (SNVs) contributing to HCC recurrence were identified using whole-exome sequencing of 5 DNA samples extracted from a single HCC patient with HBV-induced cirrhosis. SNVs were verified in primary HCC (n = 87), recurrent HCC (n = 34), and benign liver disease with cirrhosis tissues (n = 43). A candidate gene was identified, and its association and function in HCC development and recurrence were examined. RESULTS: 177 SNVs were identified and 70 SNVs were verified. A MPPE1 missense mutation on chr18_11897016 was the most frequent mutation (16.5%) in primary and recurrent HCC tissues, occurring with a higher frequency in recurrent HCC than primary HCC or benign liver tumor tissues. The MPPE1 mutation was significantly associated with HCC recurrence (P = .003), TNM stage (P = .002), and Child-Pugh classification (P = .039), and was an independent risk factor for HCC recurrence (HR = 1.969; 95%CI = 1.043-3.714, P = .037). Analysis of publically available data deposited in the GEO and TCGA showed MPPE1 expression levels were significantly increased in HCC tumor samples compared to adjacent nontumor tissues. The knockdown of MPPE1 in HCC cell lines significantly inhibited cell proliferation, migration and invasion, induced cell cycle arrest and apoptosis in vitro, and inhibited xenograft tumor growth in nude mice in vivo (P < .05). CONCLUSIONS: MPPE1 is a novel gene associated with HCC malignancy and recurrence.

13.
J Thorac Dis ; 12(8): 4057-4069, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32944317

RESUMO

Background: To estimate the incidence and susceptible factors of fatal toxic effects related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods: PubMed and Embase were thoroughly searched for clinical trials based on the following terms and corresponding Medical Subject Heading ones: "erlotinib", "gefitinib", "afatinib", "dacomitinib", "osimertinib", and "non-small-cell lung cancer (NSCLC)". A total of 53 eligible cohorts with 9,569 participants were collected. Results: A total of 105 cases of fatal toxic effects related to EGFR-TKIs occurred in 53 cohorts. The overall incidence was 1.33% [95% confidence interval (CI): 1.08-1.63%]. The odds and incidence were apparently higher in Japanese group (compared with non-East Asian group) [2.72 vs. 1.30, P=0.015; odds ratio (OR): 2.26, 95% CI: 1.17-4.37, P=0.015], in first-line treatment group (compared with EGFR-TKI retreatment group) (1.54 vs. 0.69, P=0.028; OR: 2.41, 95% CI: 1.10-5.26, P=0.028), and in the trial phase II (compared with trial phase III) (1.82% vs. 1.11%, P=0.009; OR: 1.73, 95% CI: 1.15-2.62, P=0.009). Notably, the Japanese group was higher than non-East Asian group after controlling for the treatment-line and trial phase (OR: 2.16, 95% CI: 1.12-4.16, P=0.022). Interstitial lung disease (ILD) was predominant in 29 fatal causes followed by pneumonia, respiratory failure and diarrhea. Conclusions: The overall incidence of fatal toxic effects related to EGFR-TKIs was 1.33%, and the major fatal cause was ILD, followed by pneumonia, respiratory failure and diarrhea. The susceptible factor of fatal toxic effects related to EGFR-TKIs was the Japanese group. This study provided a capability for clinicians to predict and detect high-risk populations of fatal toxic effects.

14.
Chin Med ; 15: 102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32994803

RESUMO

Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.

15.
J Clin Nurs ; 29(21-22): 4161-4170, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32757428

RESUMO

AIMS AND OBJECTIVES: To evaluate the mental health status, stressors and self-adjustment of nurses in isolation wards at different periods in Wuhan, China. BACKGROUND: Mental health issues easily occurred among the frontline medical workers of a major epidemic. However, the stressors and psychological adjustments experienced by nurses have not been well described. This is crucial to improving clinical quality and nursing safety and ensuring nurses' physical and psychological health. METHODS: We performed a cross-sectional prospective study using the Self Reporting Questionnaire-20, stressor and self-adjustment questionnaire administered to frontline nurses in Wuhan at two time points: after they had worked in isolation wards for 7-10 days (T1 ) and 2 months (T2 ). This paper complies with the STROBE reporting guideline for cross-sectional studies. RESULTS: T1 has 92 respondents, and T2 has 86. The positive rates of mental health problems were 26.09% and 9.30%, respectively, showing significantly different in the two periods. The main factors influenced mental health were self-perceived stress and only child status. The most common stressors were as follows: a large infected population, high infectivity; concerned about family's health status; high mortality if not treated in time (T1 ); and long duration of the epidemic, separate from family for a long time (T2 ). In terms of self-adjustment, 97.83%(T1 )/88.04%(T2 ) of nurses thought it was necessary, but 9(T1 ) /5(T2 ) chose to avoid addressing it, and 8(T1 ) /5(T2 ) utilised a professional psychological counselling hotline. CONCLUSIONS: Mental health problems among frontline nurses fighting COVID-19 need special attention, so administrators should offer timely counselling and strengthen effective psychosocial support to improve their mental resilience. RELEVANCE TO CLINICAL PRACTICE: This study surveyed the mental problems and self-adjustment status among nurses working Wuhan during the outbreak of COVID-19, to provide administrators with a scientific basis to effectively intervene.


Assuntos
COVID-19/enfermagem , Ajustamento Emocional , Recursos Humanos de Enfermagem no Hospital/psicologia , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Inquéritos e Questionários
16.
Medicine (Baltimore) ; 99(28): e21023, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664107

RESUMO

Multidrug-resistant tuberculosis (MDR-TB) threatens global public health. Poor access to health care due to financial hardship contributes to further transmission of the disease. The study aimed to:A cross-sectional study was conducted in 2 hospitals designated for MDR-TB from January to August 2018. Data were collected by interviewing eligible MDR-TB outpatients and reviewing the medical records. The magnitude of financial burden was documented by total cost and distribution of cost components. Catastrophic payments were measured by 2 indicators: catastrophic health expenditure (CHE) and catastrophic total costs (CTC), both of which were estimated by incidence and intensity. Their associated factors were determined using logistic regression models.Of 161 households affected by MDR-TB, the average total costs due to MDR-TB treatment in the first year was US$ 8266 and consisted of 72% direct medical costs, 5% direct non-medical costs and 23% indirect costs (income loss). Thirty seven percent of direct medical costs were covered by insurance. Overall, the incidence of CHE and CTC was 68.3% and 87.0%, respectively. Both incidence and intensity for the 2 defined catastrophic costs increased when a households income decreased. Five significant factors of catastrophic costs were low household income, absence of students in a family, hospital length of stay, male gender, and job/productivity loss.Households with MDR-TB patients shouldered a high financial burden which was mainly driven by direct medical costs and income loss in Guizhou. Greater catastrophic payments were associated with hospital length of stay and socioeconomic status, especially had a dose-response relationship with households income. Our findings suggest that financial and social protection of local policies for MDR-TB should be improved by preparing a uniform and comprehensive insurance package to cover sufficiently direct medical costs, and introducing social pro-poor assistance policies for risk families to protect them from financial hardship.


Assuntos
Efeitos Psicossociais da Doença , Tuberculose Resistente a Múltiplos Medicamentos/economia , Adulto , China , Estudos Transversais , Características da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Clin Chim Acta ; 507: 194-198, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32360157

RESUMO

BACKGROUND: The etiology of Autoimmune thyroid disease (AITD) in pediatric age is multifactorial and mainly implicated with immune disorder. Previous studies have reported that interleukin-21 (IL-21) and vitamin D play crucial roles in autoimmune diseases. We investigated the correlation between IL and 21 and 25(OH)D and their potential role in the pathogenesis of AITD. METHODS: Total of 54 primary Graves disease (GD) patients, 36 Hashimato's thyroditis (HT) cases and 30 healthy subjects from The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University from September through November 2017 to 2019. The serum concentrations of IL-21, 25(OH)D, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antibodies against receptor for TSH (TRAb) and thyroglobulin antibody (TGAb) were determined. RESULTS: The serum concentration of 25(OH)D was lower while IL-21 was higher in the GD patients and HT patients than in the control patients. Serum 25(OH)D concentration was negatively correlated with TPOAb and TGAb while serum IL-21 concentration was positively correlated with TPOAb, TGAb and TRAb in the HT group. Moreover, the serum concentration of 25(OH)D had a significant negative correlation with serum IL-21 concentration in the HT and GD children before or after treatment. Therefore, we studied the correlation between IL and 21 and 25(OH)D, and infer that they play a role in AITD. Moreover, adding Vitamin D could inhibit the expression concentrations of TPOAb, TGAb and IL-21. CONCLUSION: IL-21 and Vitamin D may be involved in the occurrence and development of AITD. Targeting IL-21 and Vitamin D may be a promising therapeutic approach for AITD in the future.


Assuntos
Interleucinas/sangue , Tireoidite Autoimune/sangue , Vitamina D/sangue , Grupo com Ancestrais do Continente Asiático , Criança , Feminino , Humanos , Masculino , Tireoidite Autoimune/diagnóstico
18.
J Cancer Res Clin Oncol ; 146(7): 1867-1876, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32221744

RESUMO

PURPOSE: Approximately 30% of NSCLC patients cannot obtain tissue sample or sufficient tissue sample for molecular subtyping. Cell-free circulating tumor DNA (ctDNA) in plasma is a potential alternative specimen type to assess genomic variants in patients with non-small cell lung cancer (NSCLC). The purpose of this study was to identify the genomic alteration profile of ctDNA in real-world Chinese NSCLC patients. METHODS: A total of 325 subjects with pathological diagnosis of NSCLC were enrolled. 10 ml Peripheral blood was collected in streck tube, and ctDNA NGS analysis was carried out using an Ampliseq-based 11-gene panel. RESULTS: 295 out of 325 patients (90.8%) had detected ctDNA results. In 62.1% (183/295) of these cases, at least one genomic alterations was detected. Frequency altered genes were EGFR (27.8%), TP53 (22.7%), KRAS (21.36%), and PIK3CA (4.75%). EGFR mutation was associated with female, younger age (< 65 years), and adenocarcinoma. The most common mutations in EGFR were L858R (39.4%), exon19 deletions (31.73%), and T790M (18.3%); G13S was the most common alterations in KRAS. TP53 mutation was most occurred in exon7 and exon8. TP53 mutation was significantly more common in patients with history of radiochemotherapy/chemotherapy therapy, and T790M was mainly found in patients with TKIs treatments. Co-existence EGFR mutation with KRAS and different multiple gene co-mutation panels were detected. CONCLUSION: In Chinese NSCLC patients, EGFR mutation was significantly associated with female, younger age (< 65 years), and adenocarcinoma. Genomic profiles of NSCLC were associated with the treatment history; TP53 mutation was significantly more frequent in the patients with history of radiochemotherapy/chemotherapy therapy. Various multiple genes co-mutation panels, especially EGFR and KRAS co-mutation, were observed in the ctDNA of Chinese NSCLC patients.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante , DNA de Neoplasias , Genômica , Neoplasias Pulmonares/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Progressão da Doença , Feminino , Frequência do Gene , Genômica/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos
19.
J Viral Hepat ; 27(3): 224-232, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31954089

RESUMO

Covalently closed circular DNA (cccDNA), which is stably present in the nucleus of hepatocytes, is an important indicator for evaluating antiviral efficacy. Since cccDNA quantification requires an invasive procedure, serum biological markers that can effectively reflect the transcriptional activity of intrahepatic virus and the efficacy of treatment are required. Here, from the aspects of virus and host, we outline the focus of clinical research of HBV in recent years, including HBV RNA, empty virus, hepatitis B core-related antigen and changes in the immune response. We briefly discuss their significance in predicting disease activity and monitoring treatment response in chronic hepatitis B. On this basis, some issues worthy of attention in laboratory diagnosis are proposed.


Assuntos
Hepatite B Crônica/diagnóstico , RNA Viral/sangue , Biomarcadores/sangue , Técnicas de Laboratório Clínico , DNA Circular/análise , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/terapia , Hepatócitos/virologia , Humanos
20.
Int J Oncol ; 56(1): 18-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746420

RESUMO

Hepatitis B virus (HBV)­related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non­coding RNAs (lncRNAs), which are non­coding RNAs >200 nt in length that were previously considered to be transcriptional noise, have been found to be dysregulated in HBV­related HCC with the help of high­throughput omics techniques. Subsequent investigations revealed that aberrant expression of lncRNAs may affect the risk of HBV­related HCC through diverse mechanisms, including epigenetic silencing of transcriptional activation, alternative splicing, molecular sponging, modulating protein stability, and by serving as precursors of miRNAs. Although the sensitivity and specificity of lncRNAs must be further validated, a number of circulating lncRNAs have been identified as useful biomarkers for HBV­related HCC. In addition to these findings, recent studies also unveiled that certain genetic polymorphisms in lncRNAs may affect the occurrence and prognosis of HBV­related HCC. The aim of the present review was to provide an overview of the mechanisms underlying the involvement of lncRNAs in HBV­related HCC. Subsequently, lncRNAs found to be dysregulated in HBV­related HCC were focused on and current findings on circulating lncRNAs and their genetic polymorphisms were discussed.


Assuntos
Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Interações Hospedeiro-Patógeno , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , RNA Longo não Codificante/genética
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