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1.
Brief Funct Genomics ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32058568

RESUMO

CRISPR/Cas9, as a new genome-editing tool, offers new approaches to understand and treat diseases, which is being rapidly applied in various areas of biomedical research including sepsis field. The type II prokaryotic CRISPR/Cas system uses a single-guide RNA (sgRNA) to target the Cas9 nuclease to a specific genomic sequence, which is introduced into disease models for functional characterization and for testing of therapeutic strategies. This incredibly precise technology can be used for therapeutic research of gene-related diseases and to program any sequence in a target cell. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. In this review, we focus on the basic principles, advantages and limitations of CRISPR/Cas9 and the use of the CRISPR/Cas9 system as a powerful tool in sepsis research and as a new strategy for the treatment of sepsis.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 12-17, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027246

RESUMO

OBJECTIVE: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS). METHODS: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (<60 years old) were compared. RESULTS: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively. CONCLUSION: The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

3.
Mol Med Rep ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32016472

RESUMO

Non­small cell lung cancer (NSCLC) is prevalent worldwide. Lung squamous cell carcinoma (LUSC) is one of the main subtypes of NSCLC yet, currently, few biomarkers are available for the diagnosis of LUSC. The present study aimed to investigate the expression and role of adenosine deaminase RNA specific B1 (ADARB1) in lung squamous cell carcinoma (LUSC). Integrative bioinformatics analysis was used to identify the effects of ADARB1 expression on the occurrence and prognosis of LUSC. The expression of ADARB1 was further examined by immunohistochemistry (IHC). Bioinformatics analysis suggested that ADARB1 was downregulated in LUSC, serving as a potential tumor suppressor, and these results were verified by IHC performed on a lung cancer tissue array. Clinical studies suggested that ADARB1 expression and methylation levels were significantly associated with patient characteristics in LUSC. Moreover, ADARB1 global methylation levels were upregulated in LUSC tissues compared with normal lung tissues. Higher methylation levels of cg24063645 were associated with shorter overall survival time of patients with LUSC. A negative correlation was identified between ADARB1 and epidermal growth factor receptor (EGFR) expression in LUSC. Using the Gene Expression Omnibus database, it was suggested that the expression of ADARB1 in LUSC was significantly different compared with that in lung adenocarcinoma. Furthermore, protein­protein interactions were studied and a biological process annotation analysis was conducted. The present study suggested that ADARB1 was downregulated in LUSC; therefore, ADARB1 may serve as a specific biomarker and a potential therapeutic target for LUSC.

4.
Biomed Pharmacother ; 125: 109825, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32036208

RESUMO

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It has been reported that carvacrol (CAR) possesses a wide range of biological activities. The effects of CAR on diabetes-induced vasculopathy remain unknown. In this study, diabetic mice were created by the intraperitoneal injection of streptozotocin (STZ) in male C57BL/6 J mice to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and to investigate the underlying mechanisms. We found that CAR decreased blood glucose levels in diabetic mice. Moreover, CAR ameliorated diabetes-induced aortic morphological alterations, as evidenced by an increased thickness in the intima-media width and an increased number of vascular smooth muscle cells (VSMCs) layers. Further studies revealed that CAR inhibited hypercontractility in the aortas of diabetic mice and VSMCs in response to hyperglycemia, as evidenced by the relaxation of phenylephrine(PE)-induced vasoconstriction, the decreased expression of smooth muscle (SM)-α-actin, and the increased expression of Ki67 and proliferating cell nuclear antigen (PCNA). Furthermore, the PI3K/Akt signaling pathway was inhibited in the aortas of diabetic mice and VSMCs in response to hyperglycemia, while CAR treatment activated the PI3K/Akt signaling pathway. In conclusion, our results strongly suggest that CAR plays a protective role in diabetes-induced aortic hypercontractility, possibly by activating the PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy.

5.
Respir Med ; 162: 105871, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32056672

RESUMO

BACKGROUND: Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication. OBJECTIVE: Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis. METHODS: We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation. RESULTS: The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 µg/ml. CONCLUSIONS: Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa.

6.
Colloids Surf B Biointerfaces ; 189: 110819, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32023509

RESUMO

To improve mechanical, tribological and biological performances of polyetheretherketone (PEEK) for artificial joints applications, molybdenum disulfide (MoS2, MS) nanosheets were incorporated into PEEK to fabricate MS/PEEK biocomposites (MPC) with MS content of 4 w% (MPC4) and 8 w% (MPC8). The results revealed that the MS nanosheets with the size of about 400 nm and sheet thickness of about 70 nm were distributed into PEEK matrix, and surface roughness as well as hydrophilicity of MPC increased with the MS content increasing. Moreover, the compressive strength and shore hardness of the MPC were accordingly enhanced. Furthermore, the coefficient of friction of the MPC decreased while the wear resistance of the MPC increased with the MS content increasing in both water-sliding and dry-sliding contact. In addition, rat bone marrow derived stromal cells adhered and proliferated on the composites, indicating that the MPC had no adverse influences on cell behaviors, indicating good cytocompatibility. The results demonstrated that incorporation of MS nanosheets into PEEK produced biocomposites with improved mechanical, tribological and biological performances. MPC8 with no cytotoxicity would have a great potential for artificial joints applications.

7.
J Bone Miner Res ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020683

RESUMO

Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

8.
Eur J Pharm Biopharm ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006605

RESUMO

We have observed an interesting phenomenon in which grinding of freeze-dried monoclonal antibody X (mAb-X) formulation powder resulted to significant protein sub-visible particles (SbVPs) in the reconstituted liquid, which could only be observed by sensitive particle analytical methods such as MFI and DLS. Effects of grinding temperature and the free radical scavengers methionine and 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidin-yloxy free radical (CTPO) on the formation of SbVPs were also evaluated. Free radicals were observed by EPR and the amount of free radicals was correlated to the sample temperature prior to grinding. Formation of SbVPs could be partially inhibited by methionine and CTPO. The amount of SbVPs formed was dependent on the amount of free radicals / sample temperature prior to grinding. At higher temperatures, more free radicals and SbVPs formed. Other than the previously known protein degradation due to high temperature formed during mechanical grinding, we propose an unreported and supplementary mechanism, i.e., the formation of free radicals (i.e., due to break of C-O or C-S bonds) in the dried state during mechanical grinding, leading to protein particle formation in the reconstituted solution. Our observation suggested that mechanical grinding of protein powder should be avoided or used cautiously (i.e., grinding temperature, strength and time) and the effects on radical and particle formation be fully evaluated.

9.
Asian J Androl ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32031084

RESUMO

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32036417

RESUMO

INTRODUCTION: Open fractures are associated with high rates of complication, morbidity and high economic costs. To improve outcomes, an open extremity fracture clinical pathway that protocolized surgical management and encouraged multidisciplinary collaboration was implemented in our institution. This study evaluates the clinical outcomes before and after the implementation of the pathway. METHODOLOGY: Retrospective review of open tibial and femur fractures covering the 2 year periods before and after pathway implementation was conducted. Patient demographics, fracture location, fixation methods and Gustilo-Anderson classification type were recorded. Primary outcomes include complications of wound infection, implant infection, delayed/non-union and flap failure occurring in a 1 year follow-up period. Secondary outcomes include length of hospital stay, time from emergency department (ED) entrance to first wound debridement, time from ED to flap coverage and total number of operations required. RESULTS: A total of 43 pre-pathway and 46 post-pathway patients were included in this study. There was a significant reduction in length of hospital stay, a 37.5% decrease from a median of 11.2 to 7 days after pathway implementation. There was also a significant decrease in the number of fractures fixed with external fixators from 47 to 26%. No significant differences were found for the other secondary variables. In a subgroup analysis of type III fractures, there was a significant decrease in length of hospital stay as well as the number of operations required. Median length of hospital stay decreased by 46.7% from 15 to 8 days and total number of operations decreased by 50% from a median of four operations to two operations. CONCLUSION: This study demonstrates that the implementation of an open extremity fracture clinical pathway significantly reduces the proportion of external fixation surgeries, length of hospital stay, and number of operations in patients with open tibial and femur fractures, without compromising complication rates.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32037278

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Increasing evidence indicates a close relationship between HCC and the human microbiota. Herein, we reviewed the important potential of the human microbiota as a diagnostic biomarker of HCC. DATA SOURCES: Several innovative studies have investigated the characteristics of the gut and oral microbiomes in patients with HCC and proposed that the human microbiome has the potential to be a diagnostic biomarker of HCC. Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords "microbiota" or "microbiome" or "microbe" and "liver cancer" or "hepatocellular carcinoma", and the results of clinical and experimental studies were analyzed. RESULTS: Specific changes occur in the human microbiome of patients with HCC. Moreover, the gut microbiome and oral microbiome can be used as non-invasive diagnostic biomarkers for HCC. Furthermore, they also have certain diagnostic potential for precancerous diseases of HCC. The diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future. CONCLUSIONS: The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC. The human microbiome may be widely used in the diagnosis, treatment and prognosis for multiple system diseases or cancers in the future.

12.
J Hazard Mater ; 390: 122190, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32014653

RESUMO

Metal-organic framework based carbon material UC-X was prepared by template method, and adopted to remove cephalosporins from aqueous solution. The effect of templates including cetyltrimethyl ammonium bromide and sodium laurate was discussed. The UC-0.1 with the pore size of 5.38 nm has the best adsorption. According to FTIR spectrum, with the gradual increase of sodium laurate, the functional groups like CO increased, which promoted the adsorption capacity of cefepime in UC-X materials from 42.52 to 84.23 mg⋅g-1. The optimal conditions for the adsorption of cefepime were determined by the response surface method: the adsorption temperature was 25.8 °C, the initial pH value was 6.11, and the ionic strength was 1.13 g·L-1. Under the best adsorption condition, the adsorption-desorption experiments showed that the adsorption capacity of UC-0.1 material decreased by less than 10 % after five times usage, which indicated that its recycling property was competitive. The adsorption process conformed to the mixed-order kinetic model, and the error of equilibrium adsorption capacity between model fitting and actual experiments is not more than 1 %. The overall results of adsorption isotherm model and thermodynamic analysis demonstrated that Redlich-Peterson isothermal model could describe the adsorption process better.

13.
Sci Total Environ ; 716: 137027, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32044485

RESUMO

Exposure to fine particulate matter (PM2.5) is associated with cardiovascular disease risk. To date, there are few studies on short-term PM2.5 exposure in different microenvironments and its impact on immediate health effects, particularly in the Southeast Asia region. This study assessed PM2.5 concentrations in different microenvironments in a densely populated city in the tropics using low-cost personal PM2.5 sensors as well as their associations with acute cardiovascular health outcomes. A total of 49 adult participants affiliated with the National University of Singapore (NUS) community were recruited. Personal low-cost sensors were used to measure PM2.5 concentrations between September 2017 and March 2019. Demographic information and time-activity patterns were collected using questionnaires. Wilcoxon pairwise comparisons were used to determine statistical differences between PM2.5 exposures at 18 different microenvironments. Generalized Estimating Equations (GEE) models were used to assess the association between PM2.5 exposure and blood pressure as well as heart rate. All models were adjusted for age, sex, body mass index, physical activity, temperature, duration of exposure, and baseline cardiovascular parameters. Significant differences in PM2.5 concentrations were observed across different microenvironments. Air-conditioned offices and tertiary teaching spaces had the lowest (median = 13.1 µg/m3) and hawker centres had the highest (median = 32.0 µg/m3) PM2.5 concentrations. Significant positive associations between PM2.5 exposure and heart rate (ß = 0.40, p = 4.6 × 10-5) as well as diastolic blood pressure (ß = 0.16, p = 0.0077) were also observed. Short-term exposure to PM2.5 was significantly associated with higher heart rate and blood pressure. Further work is needed to investigate the variations within each type of microenvironment and expand the study to other sub-populations such as the elderly and children.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31919982

RESUMO

CO adlayers on Pt(111) electrode surfaces are an important electrochemical system and of great relevance to electrocatalysis. The potential-dependent structure and dynamics of these adlayers are complex and still controversial, especially in the CO pre-oxidation regime. We here employ in situ high-speed scanning tunneling microscopy for studying the surface phase behavior in CO-saturated 0.1 M H 2 SO 4 on the millisecond time scale. At potentials near the onset of CO pre-oxidation local fluctuations in the (2 × 2)-CO adlayer are observed, which increase towards more positive potentials. Above 0.20 V (vs. Ag/AgCl), this leads to an adlayer where CO ad apparently reside on every top site, but still exhibit a (2 × 2) superstructure modulation. We interpret this observation as a dynamic effect, caused by a small number of highly mobile point defects in the (2 × 2)-CO adlayer. As shown by density functional theory calculations, the CO lattice near such defects relaxes into a local (1 × 1) arrangement, which can rapidly propagate across the surface. This scenario, where a static (2×2) CO ad sublattice coexists with a highly dynamic sublattice of partially occupied top sites, explains the pronounced CO ad surface mobility during electrooxidation.

16.
Jpn J Clin Oncol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894237

RESUMO

BACKGROUND: Cadherin-11 (CDH11) is a type II cadherin and reported to function as an oncogene in various cancers. Our present study aims to investigate the role of CDH11 in bladder cancer (BCA). METHODS: Bioinformatics analysis was performed in four independent microarray data including 56 non-muscle-invasive bladder cancer (NMIBC) and 132 muscle-invasive bladder cancer (MIBC) tissues from Gene Expression Omnibus to screen out differentially expressed genes. Next, we detected CDH11 expression in BCA specimens and cell lines by qPCR and western blotting assays. Immunohistochemical analyses were performed in 209 paraffin-embedded BCA samples and 30 adjacent normal bladder tissues. RESULTS: Bioinformatics analysis revealed that CDH11 had a higher expression level in MIBC tissues than in NMIBC, which was consistent with our clinical BCA specimens and cell lines at both mRNA and protein levels. Immunohistochemical analysis demonstrated that over-expression of CDH11 was closely related to the histological grade, pT status, tumour size and poor outcomes of BCA patients. What's more, CDH11 (area under curve (AUC) = 0.673 and 0.735) had a better predictive value than E-cadherin (AUC = 0.629 and 0.629) and a similar discrimination with the European Organization for Research and Treatment of Cancer (EORTC) score system (AUC = 0.719 and 0.667) in evaluating potential recurrence and progression of NMIBC. Moreover, combination of CDH11 and EORTC score system was the best predictive model in predicting recurrence of NMIBC (AUC = 0.779) among the three models. CONCLUSIONS: CDH11 was a reliable therapeutic target in BCA and a useful index to predict the possibilities of recurrence and progression in NMIBC patients.

17.
Biosens Bioelectron ; 152: 111994, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941614

RESUMO

Polynucleotide kinase (PNK) plays a crucial role in phosphorylation-related DNA repair, while its real time tracking and monitoring is unexplored for limited sensitivity and robustness of current PNK sensing strategies in complex biological environment. Herein, we proposed a concatenated hybridization chain reaction (Con-HCR)-based PNK sensing platform for ultra-sensitive PNK assay and intracellular imaging. In the presence of PNK, the 5'-hydroxyl termini of hairpin Hp was phosphorylated for λ exonuclease (λ Exo)-mediated DNA cleavage reaction. This leads to the generation of initiator I for stimulating the subsequent Con-HCR-motivated assembly of branched dsDNA nanostructures with tremendously amplified Förster resonance energy transfer (FRET) signal. Owing to the multiple-responsive recognitions of PNK/exonuclease and the dual amplification of Con-HCR, the proposed method realized the sensitive and selective PNK assay as well as the screening of PNK inhibitors. This FRET-based signal transduction provides a straightforward and accurate procedure for analyzing PNK from complex cell lysate. Furthermore, the robust feature of the present system enabled their extensive application in monitoring the varied expression levels of intracellular PNK in living cells. In view of these remarkable characters, our Con-HCR-mediated PNK sensing strategy shows more potential applications in clinical diagnosis and new drug discovery researches.

18.
J Viral Hepat ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31981279

RESUMO

Noninvasive tests (NITs) for liver fibrosis are highly needed for chronic hepatitis B (CHB) patients. We aimed to investigate whether plateletcrit (PCT) could be used as a NIT in predicting liver fibrosis for CHB patients. Five hundred and sixty-seven treatment-naïve CHB patients with available liver biopsies were included. Patients were randomly divided into a derivation cohort (n = 378) and a validation cohort (n = 189). The diagnostic accuracy of PCT was evaluated using receiver operating characteristic (ROC) curves. In the derivation cohort, PCT in CHB patients with S2-S4 (0.14%), S3-S4 (0.13%) and S4 (0.12%) was lower than patients with S0-S1 (0.17%, P < .001), S0-S2 (0.17%, P < .001) and S0-S3 (0.16%, P < .001), respectively. PCT was an independent predictor of significant fibrosis (≥S2), advanced fibrosis (≥S3) and cirrhosis (S4). The area under the ROC curve (AUROC) of PCT in predicting significant fibrosis, advanced fibrosis and cirrhosis was 0.645, 0.709 and 0.714, respectively. The AUROC of PCT was higher than the aspartate transaminase to platelet ratio index (APRI) in identifying advanced fibrosis and cirrhosis, while this was comparable with APRI in identifying significant fibrosis. The diagnostic value of PCT was comparable with fibrosis-4 score (FIB-4) in predicting significant fibrosis, advanced fibrosis and cirrhosis. In the validation cohort, PCT could also identify significant fibrosis, advanced fibrosis and cirrhosis with similar diagnostic accuracy as in the derivation cohort. PCT represents a simple and inexpensive indictor for liver fibrosis in CHB patients. PCT is just as good or better than other more complex tools for staging liver fibrosis in CHB patients.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31961495

RESUMO

OBJECTIVE: To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to all-cause mortality and identify mediators in the causal pathway. METHODS: Participants from the Osteoarthritis Initiative were divided into four groups: (1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren and Lawrence grade ≥2] and knee pain); (2) knee pain only; (3) radiographic knee OA only; and (4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to all-cause mortality using a multivariable Cox-proportional model and assessed the extent to which the association was mediated by disability, physical (PCS) and mental component summary scores (MCS) of quality of life (QoL), and oral pain-relief medications (i.e. nonsteroidal anti-inflammatory drugs and opioids) use. RESULTS: Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [CI]: 1.6-3.1) for symptomatic knee OA, 0.9 (95%CI: 0.6-1.4) for knee pain only, and 2.0 (95%CI: 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95%CI: 1.0-1.4) and 1.2 (95%CI: 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use. CONCLUSION: Participants with either symptomatic or radiographic knee OA were at an increased risk of all-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31961985

RESUMO

DNAzymes have been recognized as promising transducing agents for visualizing endogenous biomarkers, while their inefficient intracellular delivery (including blunt responsibility) and limited amplification capacity (including insufficient cofactor supply) preclude their extensive biological applications. Here an exquisite autocatalytic DNAzyme (ACD) biocircuit is constructed for in vivo amplified microRNA imaging based on honeycomb MnO 2 nanosponge (hMNS)-sustained hybridization chain reaction (HCR) and DNAzyme biocatalysis. The versatile hMNS scaffolds not only deliver DNA probes, but also supply appropriate Mn 2+ -DNAzyme cofactors and intelligent magnetic resonance imaging (MRI) agents into cancer cells. Through the subsequent synergistic cross-activation between HCR and DNAzyme amplicons, the ACD amplifier turns the limited miRNA-recognition into tremendously amplified readout, thus contributing to the accurate tumor diagnosis. As a robust sensing strategy, the intelligent autocatalytic amplifier realized the microRNA imaging in vivo, thus showing great promise in clinical theranostic.

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