ABSTRACT
INTRODUCTION: Comorbidities, such as gastroesophageal reflux disease (GERD), are common in patients with rhinosinusitis (RS). However, the link between RS and GERD has not been fully understood. This study aimed to investigate the causal relationship between GERD and acute (ARS) or chronic RS (CRS), providing references for the pathogenesis and management of RS. METHODS: The data were obtained from the Integrative Epidemiology Unit Open GWAS project and FinnGen. A total of 972,838 individuals were included. The inverse variance-weighted (IVW) method was applied to obtain the primary results of the study. Weighted median, MR-Egger, and mode-based methods were used to determine the robustness of the results. Cochran's Q statistic and MR-Egger method were applied to detect heterogeneity and pleiotrophy in instrumental variables (IVs). Other sensitivity analyses included MR-PRESSO and leave-one-out analysis. RESULTS: The MR study showed that GERD was associated with an increased risk of CRS (OR: 1.36, 95% CI: 1.18-1.57, p < 0.001). The results of other analysis methods were broadly consistent with the IVW estimate. No heterogeneity was detected by Cochran's Q test (p = 0.061) and MR-PRESSO (p = 0.074). No horizontal pleiotropy was shown in IVs (p = 0.700). GERD was also associated with an increased risk of ARS (OR: 1.31, 95% CI: 1.17-1.48, p < 0.001). Some analytical results were inconsistent with the IVW estimate. No heterogeneity and pleiotropy were observed. There was no sufficient evidence for a reverse causal effect of RS on GERD. CONCLUSION: Our study supported that GERD promoted the risk of CRS and may be a potential risk factor for ARS. This provides additional support for further investigation into the mechanisms of GERD on RS.
Subject(s)
Gastroesophageal Reflux , Rhinosinusitis , Humans , Mendelian Randomization Analysis , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/epidemiology , Risk Factors , Genome-Wide Association StudyABSTRACT
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
Subject(s)
Asthma , Biological Products , Nasal Polyps , Rhinitis , Sinusitis , Humans , Asthma/drug therapy , Biological Products/therapeutic use , Chronic Disease , Consensus , Nasal Polyps/complications , Nasal Polyps/drug therapy , Omalizumab/therapeutic use , Quality of Life , Rhinitis/complications , Rhinitis/drug therapy , Sinusitis/complications , Sinusitis/drug therapy , Steroids/therapeutic useABSTRACT
Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium-derived cytokines, namely IL-25, IL-33, and TSLP, as key regulatory factors that link in immune-pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium-derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.
Subject(s)
Asthma , Rhinitis, Allergic , Sinusitis , Asthma/epidemiology , Asthma/etiology , Cytokines , Humans , Inflammation , Interleukin-33 , Sinusitis/etiologyABSTRACT
BACKGROUND: Neutrophil accumulation has been observed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the functions of neutrophils are poorly understood. Neutrophils produce neutrophil extracellular traps (NETs), which are involved in a variety of chronic inflammatory pathologies. LL-37 is the only member of the cathelicidin family in human. OBJECTIVE: Our aims were to examine the presence of NETs in CRSwNP and to investigate the regulatory effect of LL-37 on NET formation. METHODS: Nasal polyp tissues were investigated for the presence of NETs by using immunofluorescent (IF) staining. The expression and distribution of LL-37 were examined by using quantitative RT-PCR, ELISA, IF, and immunohistochemistry. Purified peripheral neutrophils were stimulated with LL-37 and stained with IF to identify NETs. NETs% was defined as percentage of NET-generating neutrophils to the total number of neutrophils. RESULTS: Neutrophil extracellular traps were located in the subepithelial layer of nasal polyps and control tissues. Nasal polyps had higher NETs% compared with that of controls (23.01% ± 3.43% vs 4.52% ± 1.33%, P < 0.0001). NET count was also increased in nasal polyps. NET count correlated with neutrophil count (r = 0.908, P < 0.001). LL-37 protein and mRNA levels were upregulated in nasal polyps. LL-37 was distributed in the epithelial and subepithelial layer and mainly expressed by neutrophils. Moreover, LL-37 promoted peripheral neutrophils to form NETs in a dose-dependent manner ex vivo. Interestingly, dexamethasone did not inhibit the effect of LL-37 on inducing NET formation. Furthermore, peripheral neutrophils from CRSwNP patients were more susceptible to LL-37-mediated NET formation, compared with neutrophils derived from control subjects. In addition, NETs released LL-37 in vivo and ex vivo. CONCLUSION: Neutrophil extracellular traps are significantly increased in nasal polyps and LL-37 induces NET formation in CRSwNP patients. These findings indicate that NETs may contribute to the pathogenesis of neutrophilic inflammation in CRSwNP.
Subject(s)
Antimicrobial Cationic Peptides/immunology , Extracellular Traps/immunology , Nasal Polyps/immunology , Neutrophils/immunology , Rhinitis/immunology , Sinusitis/immunology , Adolescent , Adult , Aged , Chronic Disease , Female , Humans , Male , Middle Aged , Nasal Polyps/pathology , Neutrophils/pathology , Rhinitis/pathology , Sinusitis/pathology , CathelicidinsABSTRACT
BACKGROUND: The implementation of allergen immunotherapy (AIT) requires extensive knowledge of allergen distribution in the region to identify high-risk regions for AIT utilization. However, the geographical distribution patterns of the major Dermatophagoides allergens in China remain unclear despite the increasing prevalence of these allergens. METHODS: We performed comprehensive database searches of articles demonstrating the distribution patterns of Dermatophagoides-sensitized allergic rhinitis (AR) and allergic asthma (AA) in China, published between 1990 and 2017. RESULTS: We retrieved 163 articles encompassing 114,302 allergen-positive cases to generate the distribution maps. The rate of sensitization to Dermatophagoides pteronyssinus(D. pteronyssinus)and Dermatophagoides farinae (D. farinae) was similar in patients with AR (75.1 vs. 75.2%, p > 0.05) but not in those with AA (78.5 vs. 77.7%, p = 0.041). Patients with AR and AA shared similar regional distribution patterns of both D. pteronyssinus and D. farinae sensitization, which were highest in the southern and central parts of China and lowest in the northern regions, especially in the Northwest. The overall rate of sensitization to D. pteronyssinus and D. farinae was significantly higher in patients with AA (p < 0.001). Additionally, the annual mean temperature and humidity were the 2 major determinants of D. pteronyssinus and D. farinae sensitization in AR and of D. pteronyssinus sensitization in AA, whereas the annual mean temperature was the sole determinant for D. farinae sensitization in AA. CONCLUSION: These findings may inform clinicians of the strategies for the prevention of Dermatophagoides sensitization and may be of benefit to the future clinical management of allergic diseasesassociated with sensitization to Dermatophagoides mites.
Subject(s)
Antigens, Dermatophagoides/immunology , Asthma/epidemiology , Asthma/immunology , Pyroglyphidae/immunology , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/immunology , Animals , China/epidemiology , Environment , Female , Geography, Medical , Humans , Immunization , Male , Prevalence , Public Health Surveillance , ROC CurveABSTRACT
Tight junctions (TJs) alteration is commonly seen in airway inflammatory diseases. Oncostatin M (OSM) is an inflammatory mediator associated with chronic rhinosinusitis with nasal polyps (CRSwNP). We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for influenza A virus (IAV). However, its role in TJs alteration and the effects of IAV on inducing OSM expression in nasal epithelium remains to be further investigated. In this study, OSM and TJs expression was measured and compared between inferior turbinate from healthy controls and nasal polyps from CRSwNP. Additionally, hNECs cultured at air-liquid interface (ALI) were infected with H3N2 influenza virus to study the role of influenza virus in inducing epithelial OSM expression as a possible means of exacerbation. The expression of ZO-1, claudin-1, and occludin was markedly decreased and correlated negatively with that of OSM in CRSwNP. By using the in vitro hNEC model, H3N2 infection resulted in significantly increased OSM expression (2.2-, 4.7- and 3.9-fold higher at 8, 24, and 48â¯h post-infection vs. mock infection). Furthermore, OSM is found to co-localize with ciliated and goblet cells in hNECs infected with H3N2 influenza virus. Our findings demonstrated that increased OSM expression is implicated in CRSwNP as a possible mechanism of TJs' impairment, which can be further augmented following influenza infection via epithelial OSM expression, possibly contributing to exacerbations.
Subject(s)
Influenza A Virus, H3N2 Subtype/genetics , Influenza, Human/genetics , Nasal Mucosa/metabolism , Nasal Polyps/genetics , Oncostatin M/genetics , Rhinitis/genetics , Sinusitis/genetics , Adult , Case-Control Studies , Cell Differentiation , Chronic Disease , Claudin-1/genetics , Claudin-1/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelial Cells/virology , Female , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Influenza A Virus, H3N2 Subtype/growth & development , Influenza A Virus, H3N2 Subtype/metabolism , Influenza, Human/metabolism , Influenza, Human/pathology , Influenza, Human/virology , Male , Middle Aged , Nasal Mucosa/pathology , Nasal Mucosa/virology , Nasal Polyps/metabolism , Nasal Polyps/pathology , Nasal Polyps/virology , Occludin/genetics , Occludin/metabolism , Oncostatin M/metabolism , Primary Cell Culture , Rhinitis/metabolism , Rhinitis/pathology , Rhinitis/virology , Signal Transduction , Sinusitis/metabolism , Sinusitis/pathology , Sinusitis/virology , Tight Junctions/metabolism , Tight Junctions/pathology , Tight Junctions/virology , Zonula Occludens-1 Protein/genetics , Zonula Occludens-1 Protein/metabolismABSTRACT
PURPOSE: Evidences showed improvements in clinical asthma outcomes following endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) patients with asthma. However, pulmonary function benefits have remained controversial up to date. The goal of this study was to conduct a systematic review and meta-analysis to investigate the effects of ESS on pulmonary function tests in CRS patients with asthma. METHODS: Pubmed, Embase and Cochrane Library were searched up to March 2018 to obtain relevant studies. The researches that evaluated the effects of ESS on pulmonary function in CRS patients with asthma and had at least one parameter of pulmonary function tests before and after surgery were included in the study. RESULTS: A total of 13 studies containing 421 patients satisfied the eligibility after judgment by 2 reviewers. These included three RCTs and ten case series. The heterogeneity in parameters of spirometry and difference in data presented forms across studies along with the lack of standard deviation of some data make it difficult to synthesize results. If data were unavailable for meta-analyses, descriptive statistics were used to report study outcomes. After qualitative and quantitative analysis, the weighted mean change after ESS in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75%) was 0.21 L/s (95% CI 0.12-0.30); eight of ten studies supported that forced expiratory volume at 1 s (FEV1) improved after ESS; five of six studies supported that peak expiratory flow (PEF) improved after ESS. However, strength of evidence is generally low to insufficient. CONCLUSION: A generally low-quality evidence supports the association between ESS and improvements in FEF25-75%, FEV1 and PEF. A few studies met inclusion criteria for meta-analysis, which indicates the need for more high-quality studies to determine the effect of ESS.
Subject(s)
Asthma/physiopathology , Respiratory Function Tests/methods , Rhinitis , Sinusitis , Asthma/complications , Asthma/diagnosis , Chronic Disease , Endoscopy/methods , Humans , Postoperative Period , Rhinitis/complications , Rhinitis/surgery , Sinusitis/complications , Sinusitis/surgery , Treatment OutcomeSubject(s)
Air Pollutants , Air Pollution , Rhinitis, Allergic , Humans , Incidence , Air Pollution/adverse effects , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/etiology , Meteorological Concepts , China/epidemiology , Air Pollutants/adverse effects , Air Pollutants/analysis , Particulate Matter/adverse effectsABSTRACT
BACKGROUND: Forkhead box J1 (FOXJ1) plays pivotal roles in motile cilia formation. However, it remains unclear whether abnormal expression or localization of FOXJ1 in nasal mucosa tissues is associated with allergic rhinitis (AR), in which impaired mucociliary clearance is implicated. OBJECTIVE: We sought to investigate the expression and localization of FOXJ1 in inferior turbinate from patients with AR and controls. METHODS: We assayed mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 by using whole-genome expression array and quantitative real-time polymerase chain reaction. We elucidated the localization of FOXJ1 by using immunofluorescence assays in paraffin sections and primary single cells. Four patterns of FOXJ1 localization (normal, N; intermediate, I; mislocalization, M; absence, A) were defined. We developed a semiquantitative scoring system to elucidate their localization in 5 areas per paraffin section, with individual sections being assigned a score between 0 and 2. RESULTS: The mRNA levels of FOXJ1, DNAI1, DNALI1, and DNAH9 were significantly reduced in patients with AR compared with controls (all p < 0.05). The median (1st and 3rd quartile) of the FOXJ1 score was 0.4 (0.0 and 0.85) in patients with AR, and 0.2 (0.0 and 0.4) in controls (p < 0.05). For primary cytospin samples, the mean percentages of FOXJ1 localization patterns N, I, M, and A were 46.7, 10.0, 30.0, and 26.7% in patients with AR, and 82.5, 5.0, 5.0, and 7.5% in controls, respectively (p < 0.05). CONCLUSION: Downregulation and aberrant localization of FOXJ1 may be crucial characteristics of the allergic nasal mucosa.
Subject(s)
Forkhead Transcription Factors/genetics , Nasal Mucosa/metabolism , Rhinitis, Allergic/metabolism , Adult , Down-Regulation , Female , Forkhead Transcription Factors/analysis , Humans , Male , RNA, Messenger/analysis , Rhinitis, Allergic/immunology , Th2 Cells/immunologyABSTRACT
PURPOSE: Chronic tonsillitis (TC) is among the most common bacterial diseases in pediatric otolaryngology. We aimed to evaluate the expression of glycogen synthase kinase 3ß (GSK-3ß) in a cohort of children with chronic tonsillitis (TC), and the correlation between GSK-3ß activity index and inflammatory profiles of TC. MATERIALS AND METHODS: The expression of GSK-3ß was comparably evaluated between children with TC (nâ¯=â¯26) and tonsillar hypertrophy (TH, nâ¯=â¯26). GSK-3ß expression was detected by immunohistochemistry, RT-qPCR, and Western blot. The inflammatory profiles between the TC and TH groups were also evaluated. RESULTS: We found that while GSK-3ß was highly expressed in both TC and TH groups, no significant difference were detected at mRNA and protein levels between groups. The protein level of p-GSK-3ß was significantly lower in the TC group as compared to the TH group. Additionally, the inflammatory markers, including NF-κB, T-bet, and IFN-γ were higher in the TC group compared to TH group. The GSK-3ß activation index was positively correlated with the levels of NF-κB, T-bet, and IFN-γ in the TC group. CONCLUSIONS: Our findings suggested that GSK-3ß activation index was demonstrated to be a clinically applicable indicator for chronic recurrent inflammation in pediatric TC.
Subject(s)
Glycogen Synthase Kinase 3 beta/metabolism , NF-kappa B/metabolism , Phosphorylation , Tonsillitis/diagnosis , Biomarkers/metabolism , Blotting, Western , Child , Child, Preschool , Chronic Disease , Cohort Studies , Enzyme Activation/genetics , Female , Glycogen Synthase Kinase 3 beta/genetics , Humans , Male , NF-kappa B/genetics , Prognosis , Prospective Studies , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction/methods , Signal Transduction , Tonsillitis/geneticsABSTRACT
Chronic rhinosinusitis without nasal polyps (CRSsNP) is one of the most common otorhinolaryngologic diseases worldwide. However, the underlying mechanism remains unclear. In this study, the expression of glycogen synthase kinase 3 (GSK-3) was quantitatively evaluated in patients with CRSsNP (n = 20) and healthy controls (n = 20). The mRNA levels of GSK-3α and GSK-3ß were examined by qPCR, the immunoreactivities of GSK-3ß and nuclear factor-κB (NF-κB) were examined by immunohistochemistry (IHC) staining, and the protein levels of GSK-3ß, phospho-GSK-3ß (p-GSK-3ß, s9) and NF-κB were examined using Western blot analysis. We found that GSK-3 was highly expressed in both CRSsNP and control groups without significant difference in both GSK-3ß mRNA and protein levels. However, when compared with healthy control group, the GSK-3ß activation index, defined as the ratio of GSK-3ß over p-GSK-3ß, was significantly decreased, whereas the NF-κB protein abundance was significantly increased in CRSsNP group (P < 0.05). Strikingly, the GSK-3ß activation index, was highly correlated with NF-κB protein level, as well as CT scores in CRSsNP group (P < 0.05). It was also highly correlated with the mRNA expressions of inflammation-related genes, including T-bet, IFN-γ and IL-4 in CRSsNP group (P < 0.05). Our findings suggest that GSK-3ß activation index, reflecting the inhibitory levels of GSK-3ß through phosphorylation, may be a potential indicator for recurrent inflammation of CRSsNP, and that the insufficient inhibitory phosphorylation of GSK-3ß may play a pivotal role in the pathogenesis of CRSsNP.
Subject(s)
Glycogen Synthase Kinase 3 beta/genetics , NF-kappa B/genetics , RNA, Messenger/genetics , Rhinitis/diagnosis , Sinusitis/diagnosis , Adolescent , Adult , Biomarkers/metabolism , Case-Control Studies , Chronic Disease , Female , Gene Expression Regulation , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3/immunology , Glycogen Synthase Kinase 3 beta/immunology , Humans , Inflammation , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-4/genetics , Interleukin-4/immunology , Male , Middle Aged , NF-kappa B/immunology , Nasal Polyps , Phosphorylation , RNA, Messenger/immunology , Recurrence , Rhinitis/genetics , Rhinitis/metabolism , Rhinitis/physiopathology , Signal Transduction , Sinusitis/genetics , Sinusitis/metabolism , Sinusitis/physiopathology , T-Box Domain Proteins/genetics , T-Box Domain Proteins/immunologyABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive. OBJECTIVE: To investigate the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP. METHODS: In this study, sinonasal tissues were collected from 42 patients with CRSwNP (asthma, n = 17; asymptomatic AHR, n = 11; non-AHR, n = 14), 11 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 13 controls. The protein and messenger RNA levels of interleukin (IL) 25 and other cytokines in nasal polyp (NP) and control sinonasal tissues were determined by quantitative real-time polymerase chain reaction and multiplex immunoassay, respectively. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to assess the clinical relevance of IL-25. RESULTS: We found that the protein and messenger RNA levels of IL-25 were significantly increased in NP tissues compared with the control sinonasal tissues from patients with CRSwNP, patients with CRSsNP, and controls. Multivariate logistic regression revealed that the nasal IL-25 protein level and nasal and blood eosinophil counts were independent risk factors for AHR in patients with CRSwNP. According to receiver operating characteristic curve analysis, nasal tissue IL-25 had a sensitivity of 91.4% and a specificity of 62.8% (area under the curve, 0.845) at the cutoff level of 5 pg/µL for indicating AHR in this CRSwNP cohort. CONCLUSION: Our findings indicated that IL-25 was significantly increased in NP tissues and may be considered as the molecular indicator for AHR in patients with CRSwNP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02110654.
Subject(s)
Asthma/diagnosis , Interleukin-17/genetics , Nasal Polyps/diagnosis , Rhinitis/diagnosis , Sinusitis/diagnosis , Adult , Asthma/complications , Asthma/genetics , Asthma/immunology , Biomarkers/metabolism , Case-Control Studies , Chronic Disease , Eosinophils/immunology , Eosinophils/pathology , Female , Gene Expression , Humans , Interleukin-17/immunology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Nasal Polyps/complications , Nasal Polyps/genetics , Nasal Polyps/immunology , Paranasal Sinuses/chemistry , Paranasal Sinuses/immunology , Paranasal Sinuses/pathology , Pilot Projects , RNA, Messenger/genetics , RNA, Messenger/immunology , ROC Curve , Rhinitis/complications , Rhinitis/genetics , Rhinitis/immunology , Sinusitis/complications , Sinusitis/genetics , Sinusitis/immunologyABSTRACT
Accumulating evidence has demonstrated that arsenic trioxide (ATO) exhibits its anti-cancer activities in a variety of human malignancies. Recent studies have revealed that ATO regulated multiple microRNAs (miRNAs) in human cancers. However, the exact mechanism of ATO-mediated tumor suppressive function has not been fully elucidated. In the present study, we explore whether ATO governed oncogenic miR-27a in breast cancer cells by multiple methods such as MTT assay, RT-PCR, Wound healing assay, Western blotting analysis, migration, Transwell invasion assay, and transfection. Our results showed that ATO inhibited cell growth, migration, invasion, and induced cell apoptosis in breast cancer cells. Further molecular analysis dissected that ATO inhibited miR-27a expression in breast cancer cells. Moreover, inhibition of miR-27a suppressed cell growth, migration, invasion, and trigged cell apoptosis, whereas overexpression of miR-27a enhanced cell growth, motility, and inhibited apoptosis in breast cancer cells. Notably, we found that miR-27a inhibitor treatment potentiates ATO-induced breast cancer cell growth inhibition, apoptosis and motility inhibition. However, overexpression of miR-27a partly abrogated ATO-mediated anti-tumor activity. Our findings provide a novel anti-tumor mechanism of ATO involved in miR-27a for the treatment of breast cancer.
Subject(s)
Arsenicals/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cell Movement/genetics , Cell Proliferation/genetics , MicroRNAs/genetics , Oxides/administration & dosage , Antineoplastic Agents/administration & dosage , Apoptosis/drug effects , Apoptosis/genetics , Arsenic Trioxide , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Neoplasm Invasiveness , Treatment OutcomeSubject(s)
Deep Learning , Eosinophilia/diagnosis , Nasal Polyps/diagnosis , Rhinitis/diagnosis , Sinusitis/diagnosis , HumansABSTRACT
AIMS: This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a. MATERIALS AND METHODS: miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3'UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively. RESULTS: The qRT-PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects. CONCLUSIONS: This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8.
Subject(s)
Hepatitis B, Chronic/blood , Hepatitis B, Chronic/metabolism , Interleukin-8/blood , Interleukin-8/metabolism , Leukocytes, Mononuclear/metabolism , MicroRNAs/blood , MicroRNAs/metabolism , Adult , Female , Humans , Interleukin-8/genetics , MaleSubject(s)
Adrenal Cortex Hormones/administration & dosage , Interleukin-17/metabolism , Nasal Polyps/drug therapy , Nose/drug effects , Rhinitis/drug therapy , Sinusitis/drug therapy , Adult , Chronic Disease , Female , Humans , Male , Nasal Polyps/metabolism , Rhinitis/metabolism , Sinusitis/metabolismABSTRACT
PURPOSE: Parathyroidectomy is beneficial in tertiary hyperparathyroidism (THPT) consequent to chronic renal failure. The craniofacial morphology of patients who undergo total parathyroidectomy and autologous transplantation (tPTX + AT) has not been widely studied. This study assessed the efficacy of tPTX + AT in THPT and evaluated possible improvements in craniofacial features. METHODS: This retrospective analysis included patients who were diagnosed with medically refractory THPT and had undergone tPTX + AT between September 2013 and May 2021. The VAS was used to evaluate improvements in various symptoms including bone pain and pruritus. Changes in serum calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (iPTH) levels were also assessed. The impact of the procedure was assessed by comparing two-photon X-ray bone mineral density measurements obtained 1 year before and after surgery. RESULTS: The VAS of pain and pruritus decreased significantly on the first postoperative day (P < 0.05). Calcium levels changed significantly (from 2.50 ± 0.22 mmol/L to 2.10 ± 0.26 mmol/L) on postoperative day 1 (P = 0.0000); iPTH levels also declined substantially on this day, reducing from 211.00 (122.10, 252.80) to 5.04 (2.96, 9.40) pmol/L. Bone mineral density increased significantly across various regions including the greater trochanter of the femur, intertrochanteric area, total hip, and third lumbar vertebra (P < 0.05). The angles between the upper incisor and mandibular plane and the lower lip and Ricketts E line (drawn from the tip of the nose to the soft tissue area) also improved (P = 0.043, P = 0.001). CONCLUSION: Total parathyroidectomy and autologous transplantation can rapidly alleviate bone pain and skin itching in THPT. It may also improve bone density and facial soft tissue.
ABSTRACT
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.
ABSTRACT
Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease ï¼N-ERDï¼ is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis ï¼CRSï¼, asthma, and intolerance to cyclooxygenase 1 ï¼COX-1ï¼ inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Humans , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , China , Rhinitis/diagnosis , Rhinitis/therapy , Rhinitis/chemically induced , Sinusitis/diagnosis , Sinusitis/therapy , Sinusitis/drug therapy , Consensus , Asthma/diagnosis , Asthma/drug therapy , Chronic DiseaseABSTRACT
OBJECTIVE: To observe the clinical efficacy of Baidanhuang lavage fluid nasal irrigation (BLFNI) on postoperative patients with chronic sinusitis with nasal polyps (CRwNP). METHODS: Ninety postoperative patients with CRwNP were randomly assigned to two groups, the treatment group (60 cases) and the control group (30 cases). After nasal endoscopic surgery, all patients received routine therapies, while the nasal cavity perfusion device was used to irrigate. Patients in the treatment group were treated with BLFNI, while those in the control group were irrigated with physiologic saline with dexamethasone and gentamycin. The physic liquor was maintained in the nasal cavity for 15 min, 14 days as one therapeutic course: once per 3 days in first treatment course; once per 5 days in the second treatment course; once per 7 days in the third treatment course. The irrigation times gradually reduced as time went by. The VAS scoring was performed in four clinical symptoms, such as nasal obstruction, rhinorrhea, olfaction disorders, discomforts or pain in the face or head. The Lund-Kenenedy quantification scoring method was used for nasal endoscopy to assess the polyps size, mucous membrane, scar, surface scab, and quality of life (QOL). The SNOT-20 rating scales were filled to investigate the QOL. All the assessments were carried out before surgery, 1.5, 3, and 6 months, respectively. The comprehensive efficacy assessment was conducted 1 year later. RESULTS: The 1-year cure rate was 79.25% in the treatment group and 76.92% in the control group, and the total effective rate was 90.57% in the treatment group and 84.62% in the control group. There was no statistical difference between the two groups (P > 0.05). The nasal cavity cleaning time and the epithelization time was (2.15 +/- 0.13) weeks and (9.17 +/- 1.67) weeks respectively in the treatment group, earlier than those in the control group [(2.65 +/- 0.15) weeks and (10.71 +/- 3.12) weeks, P < 0.05]. At week eight 22 patients in the treatment group ended the lavage due to recovery, while 5 patients in the control group ended the lavage, showing statistical difference (P < 0.05). Compared with the control group, better results were obtained in the treatment group in relieving the total VAS score at postoperative 6 weeks and 3 months, in the single score of symptoms at 3 months after operation, the rhinorrhea at postoperative 6 months and 1 year (P < 0.05). The total endoscopic score, and the single score for nasal mucous membrane edema, and nasal secretion at postoperative 1.5 month were lower in the treatment group than in the control group (P < 0.05). The total score of SNOT-20 questionnaire, and the integrals for five major indicators at postoperative 1.5 and 3 months were lower in the treatment group than in the control group (P < 0.05). CONCLUSIONS: The perioperative application of BLFNI could alleviate postoperative mucosal inflammation, shorten the cavity cleaning time, speed up the process of epithelization, improve the QOL, and elevate the operative efficacy. Its therapeutic roles were more prominent within perioperative 1.5-3 months.