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1.
J Occup Environ Med ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33149009

RESUMO

OBJECTIVE: We aimed to examine the associations between ambient air pollutants and daily mortality in Northeast China from 2014 to 2018. METHODS: A two-stage approach was used to estimate particulate matter with an aerodynamic diameter of 10 µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) exposure and daily mortality. RESULTS: An increase of 10 µg/m of PM10 exposure and NO2 at lag of 0 to16 days was associated with the cumulative relative risk (RR) of 1.011 (95% confidence interval [CI]: 1.004, 1.019) and 1.026 (95% CI: 1.004, 1.049), respectively, in non-accident mortality. Meanwhile, significant association was observed in people aged under 60 years between SO2 exposure and respiratory mortality at lag of 0 to 9 days. CONCLUSIONS: Our findings strengthen the evidence of PM10 and NO2 exposures were independent risk for daily mortality.

2.
In Vivo ; 34(6): 3639-3648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144479

RESUMO

BACKGROUND/AIM: The association between ejection fraction (EF) and mortality in TTS patients as compared to ACS is limited. This study aims to investigate the association between EF and clinical outcomes in patients with TTS as compared to ACS. PATIENTS AND METHODS: This study compared in-hospital, and long-term incidence of clinical outcomes for 5 years in patients with TTS and ACS. The study was composed of two groups EF≥35% and EF<35%. RESULTS: The long-term mortality of the EF≥35% for 5 years was significantly higher in TTS patients as compared to ACS (18.1% vs. 7.7%, log-Rank; p<0.01). Irrespective of EF, a non-cardiovascular death was significantly higher in TTS as compared to ACS patients with EF≥35 (6.4% vs. 2.1%; p=0.02) and with EF<35% (21.4% vs. 7.5%; p=0.03). CONCLUSION: The long-term mortality is significantly higher in TTS as compared to ACS dominated by a non-cardiovascular cause of death at 5-years-follow-up.

3.
Mol Med Rep ; 22(6): 4567-4578, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33173977

RESUMO

The present study aimed to explore the biological functions and molecular mechanisms of the long non­coding RNA VIM antisense RNA 1 (VIM­AS1) in gastric cancer (GC). The expression of VIM­AS1 was analyzed in tissues from patients with GC and GC cell lines by reverse transcription­quantitative (RT­q)PCR. The relationship between VIM­AS1 expression and overall survival time of patients with GC was also assessed. To determine the biological functions of VIM­AS1, Cell Counting Kit­8 assay, colony formation assay, flow cytometry, wound healing assay and Transwell assay were employed. The targeting relationship among VIM­AS1, microRNA (miR)­8052 and frizzled 1 (FZD1) was verified by the dual luciferase reporter gene assay. The underlying molecular mechanism of VIM­AS1 on GC was determined by RT­qPCR and western blotting. In addition, tumor formation was detected in nude mice. The results of the present study demonstrated that VIM­AS1 was highly expressed in GC tissues and cells. In addition, VIM­AS1 expression was demonstrated to be closely related to the prognosis of patients with GC. Notably, silencing VIM­AS1 inhibited the proliferation, migration and invasion, and enhanced apoptosis of AGS and HGC­27 cells. Silencing VIM­AS1 significantly increased the protein expression levels of cleaved caspase­3, Bax and E­cadherin, but decreased the protein expression levels of Bcl­2, N­cadherin, vimentin, matrix metalloproteinase (MMP)­2, MMP­9, ß­catenin, cyclin D1, C­myc and FZD1. Additionally, silencing VIM­AS1 inhibited tumor growth in nude mice. Cumulatively, the present study demonstrated that VIM­AS1 may promote cell proliferation, migration, invasion and epithelial­mesenchymal transition by regulating FDZ1 and activating the Wnt/ß­catenin pathway in GC.

4.
Mol Med Rep ; 22(6): 5479, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174049

RESUMO

After the publication of the above paper, the authors have noticed that the affiliations were presented incorrectly; essentially, Drs Rong­qiang Yang, Peng­fei Guo, Qing­nan Meng, Ya Gao, Imran Khan, Xiao­bo Wang and Zheng­jun Cui are based at the Department of Burn and Repair Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, whereas Drs Zhao Ma and Cheng Chang are located at The School of Basic Medical Science of Zhengzhou University. Therefore, the affiliations for this paper should have appeared as follows: Rong­Qiang Yang1, Peng­Fei Guo1, Zhao Ma2, Cheng Chang2, Qing­Nan Meng1, Ya Gao1, Imran Khan1, Xiao­Bo Wang1 and Zheng­Jun Cui1. 1Department of Burn and Repair Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University; 2The School of Basic Medical Science of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. The authors regret that these errors with the author affiliations were not noticed prior to the publication of their paper, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 22: 3405-3417, 2020; DOI: 10.3892/mmr.2020.11413].

5.
Artigo em Inglês | MEDLINE | ID: mdl-33191522

RESUMO

BACKGROUND: In randomized studies, the strategy of pulmonary vein (PV) antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for ablation of PeAF. STUDY DESIGN: The PROMPT-AF study is a prospective, multicenter, randomized trial involving blinded assessment of outcomes. Patients (n = 276) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI and three linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavo-tricuspid isthmus. The follow-up duration is 12 months. The primary endpoint is the rate of documented atrial tachycardia arrhythmias of >30 seconds, without any antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation. This article is protected by copyright. All rights reserved.

6.
Int J Clin Oncol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216242

RESUMO

OBJECTIVE: Esophageal schwannoma (ES) are rare and mostly benign neurogenic tumors. The clinical misdiagnosis rate of it is high. In this study, the clinicopathologic features of ES in mainland China were studied to better understand the disease and improve the diagnosis and treatment rate. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. The keywords "esophageal schwannoma", "esophageal neurinoma" and "esophageal neurilemoma" were searched for databases such as Pubmed, EMbase, Wanfang Database and Chinese National Knowledge Infrastructure. The search time frame for database was until July 2019. Combined with our patient, the clinicopathological data and the diagnosis and treatment of ES were summarized. RESULTS: ES occurs in the upper part of the mediastinum and in the thoracic esophagus in most patients in the neck, upper and middle segments. CT and PET/CT examinations can be used for diagnosis, but the differentiation value of both benign and malignant ES is similar. The histopathological findings of forceps biopsy specimens are often difficult to diagnose, and deep tissue biopsies may increase pathological accuracy. EUS-FNA is also recommended for ES diagnosis, but it may also be misdiagnosed. Pathological features include a fusiform arrangement in a palisade-like structure or a tumor cell arranged in a network to form a loose structure. ES characteristic immunohistochemistry results showed that S-100 protein has strong immunological activity. CONCLUSION: The definitive diagnosis requires immunohistochemistry, especially immunological reaction with S-100 protein. The appropriate treatment plan should be selected according to the diameter of the lesion. The overall prognosis of ES is good, but attention should be paid to follow-up.

7.
BMJ Open ; 10(11): e039900, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154057

RESUMO

INTRODUCTION: The question of how to administer adequate chemotherapy to synchronise stereotactic body radiation therapy (SBRT) treatment strategy to maximise the benefits of neoadjuvant therapy for the improved prognosis of patients with borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer is a challenging and debatable issue. No studies have yet evaluated the efficacy of split-course SBRT as the neoadjuvant chemoradiotherapy regimen. We aimed to study whether neoadjuvant chemotherapy plus split-course SBRT results in better outcomes in BRPC and LAPC patients. METHODS AND ANALYSIS: Treatment-naïve patients with radiographically confirmed BRPC or LAPC, supporting biopsy results and no severe comorbidities will be enrolled. They will be treated with nab-paclitaxel plus gemcitabine (nab-P+Gem) chemotherapy plus split-course SBRT, followed by an investigator's choice of continuation of treatment with nab-P+Gem or surgery. nab-P+Gem chemotherapy will commence on day 1 for each of six cycles: nab-paclitaxel 125 mg/m2 intravenous infusion over approximately 30-45 min, followed by gemcitabine 1000 mg/m2 intravenous infusion over about 30 min on days 1 and 15 of each 28-day cycle. During the first and second cycles of chemotherapy, SBRT will be given as a single irradiation of 10 Gy four times (days 2 and 16 of each 28-day cycle). The primary endpoint is progression-free survival; while the secondary outcomes are the time to treatment failure, disease control rate, overall response rate, overall survival, R0 resection rate and incidence of adverse effects. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (No. 2019YF015-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT04289792.

8.
Int Immunopharmacol ; : 107164, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33172741

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy exhibiting the highest lethality. The present study aimed to identify different immune-related clusters in HCC and a robust tumor gene signature to facilitate the prognosis prediction for HCC patients. METHODS: For the 375 HCC cases collected from the dataset of Cancer Genome Atlas (TCGA), their overall survival (OS) and immune-related genes (IRGs) expression patterns were collected. Thereafter, consensus clustering was employed for grouping and functional enrichment, whereas the ESTIMATE algorithm and the CIBERSORT algorithm were used in subsequent assessment. Immunohistochemistry (IHC) was conducted to verify the protein expression of model genes in HCC and adjacent tissues. RESULTS: According to consensus clustering with 93-survival related IRGs, a total of five subgroups were found. These five clusters had different prognoses, immune statuses, and expression of immune checkpoints. Afterwards, 11 genes were enrolled for constructing the OS-related prediction model for TCGA HCC cases, which was then validated using the database of International Cancer Genome Consortium (ICGC). The protein expression of LCN2, S100A10, FABP6, PLXNA1, KITLG and OXTR were enhanced in HCC tissues relative to that in normal hepatic tissues, while the protein expression of S100A1, CCL26, CMTM4, IL1RN and RARG were reduced in HCC compared with normal tissues. In addition, different immunocyte infiltration levels between low- and high- groups were further examined. CONCLUSIONS: According to our results, the IRGs-based classifications assist in explaining the HCC heterogeneity, which may help to develop the more efficient individualized treatments.

9.
IEEE Trans Cybern ; PP2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175685

RESUMO

This article investigates the design of the ℓ2-ℓ∞ dynamic output-feedback (DOF) controller for interval type-2 (IT2) T-S fuzzy systems with state delay. For nonlinear systems, the IT2 fuzzy model is an efficient modeling method which can better express uncertainties than the (type-1) fuzzy model. In addition, state delay is also a general factor that affects system performance. After analyzing the stability of the system, based on convex linearization and the projection theorem, this article proposes a delay-dependent output-feedback controller design method. The IT2 membership functions (MFs) of the fuzzy controller are chosen to be different from those of the model so as to increase the freedom of controller selection. A membership-function-dependent (MFD) method based on the staircase MFs is applied to relax the stability analysis results. Finally, a numerical simulation example is given to illustrate the effectiveness of the results.

10.
Neurosci Bull ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196963

RESUMO

Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3-/- mice, CXCL10 did not increase the number of APs, and the SNL-induced increase of the numbers of APs in DRG neurons was reduced. Finally, CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG neurons. Pretreatment of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by CXCL10. Our data indicate that CXCR3, activated by CXCL10, mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability, which contributes to the maintenance of neuropathic pain.

11.
Asian J Androl ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33208565

RESUMO

This study aimed to assess the association between psychological disorders and erectile dysfunction (ED) in patients with different degrees of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This was a retrospective study conducted from June 2017 to October 2019 and included 182 outpatients. Patients were interviewed using the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) were used for the evaluation of CP/CPPS and ED. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety symptoms and depressive symptoms. The number of patients with mild CP/CPPS and mild ED, mild CP/CPPS and moderate-to-severe ED, moderate-to-severe CP/CPPS and mild ED, and moderate-to-severe CP/CPPS and moderate-to-severe ED was 69 (37.9%), 36 (19.8%), 35 (19.2%), and 42 (23.1%), respectively. The corresponding PHQ-9 scores of the four groups were 6.22, 7.19, 10.69, and 7.71, respectively. The corresponding GAD-7 scores of the four groups were 5.26, 6.31, 8.77, and 6.36, respectively. Among patients with moderate-to-severe CP/CPPS, the PHQ-9 and GAD-7 scores of the moderate-to-severe ED group were significantly lower than those of the mild ED group (P = 0.007 and P = 0.010, respectively). The prevalence of ED and premature ejaculation (PE) in patients with moderate-to-severe CP/CPPS was significantly higher than that in patients with mild CP/CPPS (P = 0.001 and P = 0.024, respectively). Our findings proved that the severity of ED was negatively associated with psychological symptoms in outpatients with moderate-to-severe CP/CPPS.

12.
J Integr Neurosci ; 19(3): 469-477, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070526

RESUMO

We investigated the effects of velvet antler polypeptide on cognitive impairment and the underlying mechanisms. Hydrogen peroxide-induced cell injury was used to establish an in vitro model of SH-SY5Y cells. In addition, we established an in vivo mouse model of cognitive impairment using intraperitoneal injections of scopolamine hydrobromide in strain mice. We administered three different doses of velvet antler polypeptide in this mouse model and assessed the influence of velvet antler polypeptide on the morphology of hippocampal neurons, hippocampal neuronal apoptosis, adrenocorticotropic hormone, and corticosterone activities in brain tissue samples, and the molecular and biochemical regulation of B-cell lymphoma-2, B-cell lymphoma-2 Associated X-protein, Cysteine-aspartic acid protease-3, glucocorticoid receptor, mineralocorticoid receptor, and corticotropin-releasing hormone in murine hippocampal neurons. Our data suggest that velvet antler polypeptide decreases glucocorticoid receptor, mineralocorticoid receptor, and corticotropin-releasing hormone levels and regulates the hormones released by the hypothalamic-pituitary-adrenal axis, thus suppressing neuronal apoptosis.

13.
Macromol Biosci ; : e2000299, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33043625

RESUMO

Injectable hydrogels for nonsteroidal anti-inflammatory drugs' (NSAIDs) delivery to minimize the side effects of NSAIDs and achieve long-term sustained release at the targeted site of synovial joint are attractive for osteoarthritis therapy, but how to improve its mechanical strength remains a challenge. In this work, a kind of 1D natural clay mineral material, attapulgite (ATP), is introduced to a classical cyclodextrin pseudopolyrotaxane (PPR) system to form a reinforced supramolecular hydrogel for sustained release of diclofenac sodium (DS) due to its rigid, rod-like morphology, and unique structure, which has great potential in tissue regeneration, repair, and engineering. Investigation on the interior morphology and rheological property of the obtained hydrogel points out that the ATP distributed in PPR hydrogel plays a role similar to the "reinforcement in concrete" and exhibits a positive effect on improving the mechanical properties of PPR hydrogel by regulating their interior morphology from a randomly distributed style to the well-ordered porous frame structure. The hybrid hydrogels demonstrate good shear-thinning and thixotropic properties, excellent biocompability, and sustained release behavior both in vitro and in vivo. Furthermore, preliminary in vivo treatment in an acute inflammatory rat model reveals that the ATP hybrid hydrogels present sustained anti-inflammatory effect.

14.
Chemistry ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044750

RESUMO

We report a green method for the synthesis of aryl selenocyanates via a three-component reaction of arylboronic acids, Se powder and TMSCN under metal-free and additive-free conditions. Remarkably , TMSCN acts as not only the substrate, but also the catalyst. Various selenaheterocycles can be also accessed with a catalytic amount of TMSCN.

15.
Mediators Inflamm ; 2020: 4286047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061827

RESUMO

This study is aimed at exploring the expression pattern and methylation level of G0S2 in the peripheral blood mononuclear cells (PBMCs) of myasthenia gravis (MG) patients with positive acetylcholine receptor (AChR) autoantibodies and revealing the relationship between the G0S2 methylation pattern and MG. The relationship between the NFAT family members and G0S2 was explored to reveal the regulatory mechanism of G0S2 in the pathogenesis and treatment of AChR MG. Moreover, we attempted to demonstrate the potential therapeutic mechanism of tacrolimus in AChR MG. The relative G0S2 expression level in the PBMCs of healthy people was compared with that in the PBMCs of AChR MG patients with quantitative real-time PCR (qRT-PCR). The methylation frequency of the G0S2 promoter was detected by bisulfite sequencing PCR (BSP) and pyrosequencing. A dual-luciferase reporter system was used to reveal the relationship between the G0S2 promoter and nuclear factor of activated T cells 5 (NFAT5). The qRT-PCR results showed that G0S2 expression was significantly upregulated in the B cells and CD8+ T cells of AChR MG patients but not in the CD4+ T cells, and these expression differences were significantly associated with a decrease in G0S2 methylation. NFAT5, which was speculated to bind to island 1 (p1) in the G0S2 promoter, may regulate the lymphocyte balance by regulating G0S2 gene expression but failed to affect the methylation of the G0S2 promoter. Tacrolimus therapy-induced methylation and overexpression of NFAT5 could significantly reduce the expression of G0S2 in AChR MG patients. The G0S2 gene was remarkably upregulated in the PBMCs of MG patients. NFAT5 may affect transcription initiation and downregulate G0S2 expression through p1 in the promoter, thus controlling G0S2 gene expression and regulating the lymphocyte balance. Therefore, G0S2 could be an immune regulatory factor in both AChR MG occurrence and treatment with tacrolimus.

16.
Autoimmunity ; : 1-9, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084415

RESUMO

Rheumatoid arthritis (RA) is considered to be a chronic autoimmune disease, pathogenesis of RA is complex and effective treatments for RA is still lacking. Previous studies found that microRNAs (miRNAs) play important roles in the pathogenesis of RA, and miR-223-3p is considered to be one of the possible biomarkers of RA. Recent studies have revealed that icariin alleviates RA in murine models, but the underlying mechanism needs to be further investigated. MiR-223-3p expression levels in fibroblast-like synoviocyte (RA-FLS) and patients with RA were quantified by qRT-PCR, cell proliferation was analyzed by CCK-8 and BrdU assay. Cell apoptosis was assessed by flow cytometry and western blotting. TNF-α, IL-1ß and IL-6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Dual luminescence-based reporter gene assay was conducted to confirm the possible interaction between miR-223-3p and NLRP3. Icariin inhibits proliferation and inflammation cytokines secretion, promotes apoptosis of RA-FLS cells and upregulated the expression of miR-223-3p. MiR-223-3p targets to 3'-UTR of NRLP3 and regulates its expression. MiR-223-3p inhibitor reversed the effect of icariin on RA-FLS cells function. Additionally, anti-RA activity of icariin was restored by NLRP3 inhibitor MCC950 in miR-223-3p knockdown RA-FLS cells. Icariin inhibits proliferation and inflammation, promotes apoptosis of RA-FLS cells by regulating miR-223-3p/NLRP3 signalling, which may serve as a potential therapeutic target to alleviate RA.

17.
Signal Transduct Target Ther ; 5(1): 214, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033232

RESUMO

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33012136

RESUMO

BACKGROUND: In this study we aimed to identify inflammatory patterns and predictors associated with clinical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients with different blood and tissue eosinophilia. METHODS: A total of 535 CRSwNP patients were enrolled, and the expression of 35 biomarkers, together with eosinophil and neutrophil counts in nasal polyps, were analyzed in a subset of 249 patients. Patients were stratified on the basis of blood (≥0.5 × 109 /L) and tissue (>10%) eosinophilia. Logistic regression models were applied to identify predictors of uncontrolled disease at least 1 year after surgery. Uncontrolled disease was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. RESULTS: Among 535 patients, 38.5% showed inconsistent blood and tissue eosinophilia. In 249 CRSwNP patients, subjects with concomitant blood and tissue eosinophilia (group 1) showed marked mucosal type 2 inflammation, characterized by high levels of interleukin (IL)-5, IL-13, and eotaxin-1, whereas subjects with normal blood and tissue eosinophil levels (group 4) demonstrated significant local neutrophilic inflammation with high expression of granulocyte colony-stimulating factor and subjects with selective tissue eosinophilia (group 2) showed intermediate and mixed eosinophilic and neutrophilic inflammation. Subjects with isolated blood eosinophilia (group 3) showed low expression of vascular endothelial growth factor and IL-10. Asthma, prior sinus surgery, and blood eosinophilia were the top 3 predictors for postsurgical uncontrolled disease. For subgroup analysis, sex in group 1, asthma in group 2, tissue IL-10 and immunoglobulin E in group 3, and prior sinus surgery in group 4 were the strongest predictors of uncontrolled disease, respectively. CONCLUSION: Different blood and tissue eosinophilia revealed distinct tissue inflammatory patterns in CRSwNP patients.

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