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1.
ORL J Otorhinolaryngol Relat Spec ; 85(3): 128-140, 2023.
Article in English | MEDLINE | ID: mdl-37019094

ABSTRACT

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 use
2.
Phys Chem Chem Phys ; 23(4): 2586-2593, 2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33474557

ABSTRACT

The oxy-substituted alkoxy radicals are generated from the oxidation of ethers. Their degradation path affects ozone production and the formation of the secondary organic aerosol in the atmosphere. In this work, three alkoxy radicals with methoxy (CH3O) substitution at ß, γ, and δ carbon are studied using laser-induced fluorescence (LIF) spectroscopy and theoretical calculation methods. A charge transfer (CT) excited state induced by the CH3O substitution is identified to be because of the intramolecular electron transfer from the C-O-C p orbital to the radical O p orbital. Comparison of the structure and CT transition strength between GGt and TTt conformers of the 3-methoxy-1-propoxy radical (CH3OCH2CH2CH2O) suggests that this long-range charge transfer effect is mainly a through-bond interaction. The CT excited state of CH3OCH2CH2CH2O has a conical intersection with the CO σ → O p excited state, which, hence, changes the LIF spectrum of the radical. Only the decomposition product HCHO was observed in the LIF spectrum of ß substituted radical CH3OCH2CH2O. For δ substituted radical CH3OCH2CH2CH2CH2O, the substitution effect on the radical stability is negligible and its LIF spectrum is close to that of unsubstituted alkoxy radicals. The results provide information for understanding the degradation chemistry of oxygenated hydrocarbon molecules in the atmosphere.

3.
Int Arch Allergy Immunol ; 180(1): 17-27, 2019.
Article in English | MEDLINE | ID: mdl-31104060

ABSTRACT

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 Curve
4.
Phys Chem Chem Phys ; 21(35): 19359-19364, 2019 Sep 21.
Article in English | MEDLINE | ID: mdl-31455949

ABSTRACT

A two-step photodissociation mechanism was proposed in the literature for dinitrites in the absence of direct evidence of the intermediate species. In this work, photodissociation dynamics of cis and trans 1,3-cyclohexane dinitrites are investigated by laser-induced fluorescence (LIF) spectroscopy and theoretical calculation methods. Observation of the fluorescence spectra of the 3-nitrosooxy cyclohexoxy radical provides direct experimental evidence that the intermediate species exists. The results indicate that photodissociation of dinitrites indeed follows a two-step mechanism, i.e. one of the O-NO bonds of the molecule breaks first upon 355 nm laser photolysis and generates an alkoxy radical (RO) plus NO; the alkoxy radical further dissociates in the secondary dissociation step and produces small fragments such as vinoxy etc.

5.
Proc Natl Acad Sci U S A ; 113(45): 12679-12684, 2016 Nov 08.
Article in English | MEDLINE | ID: mdl-27791058

ABSTRACT

In directed graphs, relationships are asymmetric and these asymmetries contain essential structural information about the graph. Directed relationships lead to a new type of clustering that is not feasible in undirected graphs. We propose a spectral co-clustering algorithm called di-sim for asymmetry discovery and directional clustering. A Stochastic co-Blockmodel is introduced to show favorable properties of di-sim To account for the sparse and highly heterogeneous nature of directed networks, di-sim uses the regularized graph Laplacian and projects the rows of the eigenvector matrix onto the sphere. A nodewise asymmetry score and di-sim are used to analyze the clustering asymmetries in the networks of Enron emails, political blogs, and the Caenorhabditiselegans chemical connectome. In each example, a subset of nodes have clustering asymmetries; these nodes send edges to one cluster, but receive edges from another cluster. Such nodes yield insightful information (e.g., communication bottlenecks) about directed networks, but are missed if the analysis ignores edge direction.

6.
Eur Arch Otorhinolaryngol ; 276(6): 1783-1791, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30944984

ABSTRACT

BACKGROUND: The infratemporal fossa (ITF) is located deep in the skull base. Recently, the endoscopic transoral approach has enabled maxillofacial surgeons to access the ITF using a less invasive approach compared to the traditional transfacial and endonasal endoscopic approaches. OBJECTIVE: The present study aims to provide maxillofacial surgeons with new data concerning direct endoscopic measurement and precise anatomical topography features of the endoscopic trans-lateral molar approach to ITF by comparing the endoscopic and regional anatomy of ITF. A clinical case receiving the proposed surgical approach is used to determine the feasibility of this technique. METHOD: The anatomical data were obtained by measuring the bone anatomical landmarks and analyzing the CT imaging data using GE's Advance Windows 4.1 software on 25 subjects (50 sides). Morphological pictures of the regional anatomy and endoscopic anatomy were obtained from 6 (12 sides) adult cadaver heads, and the anatomical features were described. The present study reports the management of one case using the proposed surgical approach. RESULTS: The proposed surgical approach clearly revealed neurovascular, muscular, and surgical landmarks in the ITF. The surgical case supports the minimally invasive treatment approach, which could rapidly access the ITF and completely excise benign tumors. CONCLUSION: The anatomical studies and surgical case presentation helps us understand the spatial relationship of surgical landmarks of the surgical approach to the ITF for the treatment of benign lesions in the deep cranial base area.


Subject(s)
Endoscopy/methods , Neurilemmoma/surgery , Skull Base Neoplasms/surgery , Temporal Bone/pathology , Aged , Cadaver , Female , Humans , Molar , Neurilemmoma/diagnostic imaging , Skull Base Neoplasms/diagnostic imaging
8.
Ann Allergy Asthma Immunol ; 118(4): 474-482.e1, 2017 04.
Article in English | MEDLINE | ID: mdl-28132739

ABSTRACT

BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c+ monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4+ T cells, and cytokine production by these T cells was determined by intracellular flow cytometry. RESULTS: LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86+ mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86+ mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4+ T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4+ T cells to produce higher level of IL-4 but lower level of IFN-γ. CONCLUSION: Atopic IL-17RB+ DCs can be up-regulated by LPS and promote a TH2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease.


Subject(s)
Dendritic Cells/immunology , Dendritic Cells/metabolism , Hypersensitivity, Immediate/immunology , Hypersensitivity, Immediate/metabolism , Lipopolysaccharides/immunology , Receptors, Interleukin-17/metabolism , Th2 Cells/immunology , Adult , Allergens , Biomarkers , Case-Control Studies , Cytokines/metabolism , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Immunophenotyping , Lymphocyte Activation/immunology , Male , Monocytes/immunology , Monocytes/metabolism , Respiratory Mucosa/immunology , Respiratory Mucosa/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Th2 Cells/metabolism , Young Adult
9.
Int J Mol Sci ; 18(4)2017 Mar 23.
Article in English | MEDLINE | ID: mdl-28333072

ABSTRACT

Pancreatic cancer (PC) is the most lethal type of gastrointestinal cancer, and early detection and monitoring is an urgent problem. Circulating tumor cells (CTCs) are emerging as a non-invasive biomarker for tumor detection. However, the low sensitivity is a main problem in the traditional CellSearch System for detecting CTCs, especially in patients with PC. In this study, we used negative enrichment (NE), immunofluorescence and in situ hybridization (FISH) of chromosome 8 (NE-iFISH) to capture and identify CTCs in PC patients. We showed that the NE-iFISH system exhibited a dramatically high detection rate of CTCs in PC patients (90%). The diagnostic rate of PC reached 97.5% when combining CTCs ≥ 2 and carbohydrate antigen 19-9 (CA19-9) > 37 µmol/L. The 1-year survival in the group of CTCs < 3 was significantly higher than that of CTCs ≥ 3 (p = 0.043). In addition, we analyzed the role of chromosomal instability in CTCs detection. The group of triploid (three hybridization signals of chromosome 8) CTCs ≥ 3 showed a shorter 1-year survival (p = 0.0279) and overall survival (p = 0.0188) than the group with triploid CTCs < 3. Importantly, the triploid CTC number but not the overall CTC counts could be a predictor of chemo-sensitivity. Moreover, circulating tumor microembolus (CTMs) were found in stage IV patients, and were positively related to the poor response to chemotherapy. In conclusion, the NE-iFISH system significantly improved the positive detection rate of CTCs and triploid CTC could be used to predict prognosis or the response to the chemotherapy of PC patients. CTM is a potential indicator of the chemotherapeutic effect in advanced PC patients.


Subject(s)
Early Detection of Cancer/methods , In Situ Hybridization, Fluorescence/methods , Molecular Diagnostic Techniques/methods , Neoplastic Cells, Circulating/pathology , Pancreatic Neoplasms/blood , Adult , Aged , Case-Control Studies , Cell Line, Tumor , Chromosomal Instability , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Ploidies
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(6): 880-885, 2017 Nov.
Article in Zh | MEDLINE | ID: mdl-29260525

ABSTRACT

OBJECTIVE: To explore the association between polymorphisms of miRNA biogenesis related gene DICER,DROSHA,RAN and unexplained recurrent spontaneous abortion (URSA) in Chinese women. METHODS: We recruited 217 patients with URSA (URSA group) and 390 healthy controls who were fertile women with history of more than one successful pregnancy outcome (control group) from June 2013 to December 2015 in the West China Second University Hospital of Sichuan University. The control group was recruited from regular physical examination and prepregnancy check for women of childbearing age during the same period. A case-control study was performed to analyze polymorphism of miRNA machinery genes,including DICER rs3742330,DROSHA rs10719, RAN rs14035,by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The frequencies of genotypes and alleles of DICER rs3742330,DROSHA rs10719,and RAN rs14035 showed no difference between URSA patients and control group (all P>0.05). DICER rs3742330/DROSHA rs10719 GG/TC+TT combinations were synergistically associated with increased URSA risk [odds ratio (OR)=1.657,95% confidence interval (CI)=1.006-2.731, P=0.047]. Although DICER rs3742330/RAN rs14035 GG / TT+TC combinations was significantly higher in the URSA group than in the control group,there was no statistical significance (OR=1.977,95%CI=0.956-4.087, P=0.066). However,DROSHA10719/RAN14035 TT+TC/TT+TC had no significant correlation with URSA (OR=0.958,95%CI=0.679-1.353, P=0.808). CONCLUSION: Our study demonstrated the relationship between URSA development and combined genotype of DICER rs3742330/DROSHA rs10719 GG/TC+TT.


Subject(s)
Abortion, Habitual/genetics , DEAD-box RNA Helicases/genetics , Genetic Predisposition to Disease , Ribonuclease III/genetics , ran GTP-Binding Protein/genetics , Case-Control Studies , China , Female , Gene Frequency , Humans , MicroRNAs , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Pregnancy
12.
Pediatr Res ; 78(2): 165-73, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25860501

ABSTRACT

BACKGROUND: To characterize the distribution of both tonsillar and circulating CD4(+)T-lymphocyte subsets, and to explore their clinical relevance in nonobese children with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 53 children who underwent tonsillectomy for either OSAS (n = 25) or primary snoring (PS, n = 28) were prospectively enrolled. Nineteen healthy children without any symptoms were recruited as controls. We quantified the frequencies of CD4(+)T-lymphocyte subpopulations using flow cytometry, serum-related cytokines using enzyme-linked immunosorbent assay, and key transcription factors using quantitative polymerase chain reaction (qPCR). RESULTS: Tonsillar distributions of CD4(+)T-lymphocyte subsets were comparable in the OSAS and PS subjects. The peripheral Th17/Treg ratio was positively correlated to severity as measured by apnea/hypopnea index (AHI), serum C-reactive protein and hypoxia-inducible factor-1α mRNA in the OSAS children (P < 0.05). And AHI was independently associated with the peripheral Th17/Treg ratio (P < 0.05). Furthermore, the response to surgery was associated with a significant reversal of the Th17/Treg imbalance and a concomitant relief of the proinflammatory profile in the OSAS subjects. CONCLUSION: Pediatric OSAS was associated with an altered Th17:Treg balance toward Th17 predominance. The changes in lymphocytic phenotypes that correlated with recurrent intermittent hypoxia in sleep apnea may contribute to the variance in systemic inflammation and downstream morbidities of pediatric OSAS.


Subject(s)
CD4-Positive T-Lymphocytes/cytology , Sleep Apnea, Obstructive/blood , T-Lymphocyte Subsets , Child , Child, Preschool , Female , Humans , Male , Sleep Apnea, Obstructive/surgery , Tonsillectomy
13.
J Thorac Oncol ; 19(7): 1073-1085, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38460751

ABSTRACT

INTRODUCTION: Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC. METHODS: RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety. RESULTS: Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6-25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61-0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5-17.1] versus 13.5 mo [95% CI: 12.1-14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52-0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3-5.5] versus 4.3 mo [95% CI: 4.2-4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic. CONCLUSIONS: Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Etoposide , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Male , Double-Blind Method , Antibodies, Monoclonal, Humanized/administration & dosage , Female , Etoposide/administration & dosage , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Middle Aged , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Aged , Adult , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Neoplasm Staging
14.
World J Otorhinolaryngol Head Neck Surg ; 10(2): 113-120, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38855290

ABSTRACT

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

15.
J Clin Med ; 12(6)2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36983228

ABSTRACT

BACKGROUND: Extensive knowledge of allergic multimorbidities is required to improve the management of allergic diseases with the industrialization of China. However, the demography and allergen distribution patterns of allergic multimorbidities in China remain unclear, despite the increasing prevalence of allergies. METHODS: This was a real-world, cross-sectional study of 1273 outpatients diagnosed with one or more allergic diseases in Guangzhou, the most populated city of southern China, with leading industrial and commercial centers, between April 2021 and March 2022. Seven allergic diseases (allergic rhinitis (AR), asthma (AS)/cough variant asthma (CVA), atopic dermatitis (AD)/eczema, food allergy (FA), allergic conjunctivitis (AC), drug allergy (DA), and anaphylaxis) were assessed. Positive rates of sensitization to different allergens were measured using an allergen detection system of the UniCAP (Pharmacia Diagnostics, Sweden) instrument platform to compare the groups of allergic multimorbidities against a single entity. RESULTS: There were 659 (51.8%) males and 614 (48.2%) females aged from 4 months to 74 years included in the analysis. The study participants who were diagnosed with allergic diseases had an average of 1.6 diagnoses. Overall, 46.5% (592 of 1273) of the patients had more than one allergic condition, and allergic rhinitis was the most common type of multimorbidity. Women were more likely to suffer from an allergic disease alone, whereas allergic multimorbidities were more likely to be diagnosed in men (p = 0.005). In addition, allergic multimorbidities were common in all age groups, with an incidence ranging from 37.1% to 57.4%, in which children and adolescents were more frequently diagnosed with allergic multimorbidities than adults (18-60 years old) (all p < 0.05). Allergic multimorbidity was observed throughout the year. A difference in the positive rate of allergens sensitization and total immunoglobulin E (tIgE) levels between different allergic multimorbidities was observed. CONCLUSIONS: Allergic multimorbidities were very commonly found in nearly half of all patients with allergies. The proportion of allergic multimorbidities varied with the type of disease, sex, age, and allergen distribution pattern. These findings may help clinicians to develop "One health" strategies for the clinical management of allergic diseases.

16.
RSC Med Chem ; 13(3): 280-299, 2022 Mar 23.
Article in English | MEDLINE | ID: mdl-35434624

ABSTRACT

Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC50 = 4.58 ± 0.24 µM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 µM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intracellular reactive oxygen species generation and decreased mitochondrial membrane potential. Compared with regorafenib, 5-23 displayed improved pharmacokinetic profiles in an in vivo rat model. Molecular docking and structure-activity relationship analyses were in agreement with the biological data. Compound 5-23 may be a potent anti-bladder cancer agent and this small molecule can be considered as a promising structure for further optimization.

18.
Mol Cancer Res ; 20(1): 62-76, 2022 01.
Article in English | MEDLINE | ID: mdl-34610962

ABSTRACT

Although the Sonic hedgehog (SHH) signaling pathway has been implicated in promoting malignant phenotypes of prostate cancer, details on how it is activated and exerts its oncogenic role during prostate cancer development and progression is less clear. Here, we show that GLI3, a key SHH pathway effector, is transcriptionally upregulated during androgen deprivation and posttranslationally stabilized in prostate cancer cells by mutation of speckle-type POZ protein (SPOP). GLI3 is a substrate of SPOP-mediated proteasomal degradation in prostate cancer cells and prostate cancer driver mutations in SPOP abrogate GLI3 degradation. Functionally, GLI3 is necessary and sufficient for the growth and migration of androgen receptor (AR)-positive prostate cancer cells, particularly under androgen-depleted conditions. Importantly, we demonstrate that GLI3 physically interacts and functionally cooperates with AR to enrich an AR-dependent gene expression program leading to castration-resistant growth of xenografted prostate tumors. Finally, we identify an AR/GLI3 coregulated gene signature that is highly correlated with castration-resistant metastatic prostate cancer and predictive of disease recurrence. Together, these findings reveal that hyperactivated GLI3 promotes castration-resistant growth of prostate cancer and provide a rationale for therapeutic targeting of GLI3 in patients with castration-resistant prostate cancer (CRPC). IMPLICATIONS: We describe two clinically relevant mechanisms leading to hyperactivated GLI3 signaling and enhanced AR/GLI3 cross-talk, suggesting that GLI3-specific inhibitors might prove effective to block prostate cancer development or delay CRPC.


Subject(s)
Nerve Tissue Proteins/metabolism , Nuclear Proteins , Prostatic Neoplasms, Castration-Resistant/genetics , Repressor Proteins/metabolism , Ubiquitin-Protein Ligase Complexes/metabolism , Zinc Finger Protein Gli3/metabolism , Animals , Cell Line, Tumor , Humans , Male , Mice , Mutation , Receptors, Androgen/metabolism
19.
Article in English | MEDLINE | ID: mdl-21952108

ABSTRACT

OBJECTIVE: To investigate the role of diffusion tensor magnetic resonance imaging (DT-MRI) in the evaluation of traumatic optic neuropathy (TON). METHODS: Six patients with TON underwent DT-MRI prior to decompression surgery. DTV 2 and Volume One 1.44 software were used to measure the fractional anisotropy (FA) and the mean apparent diffusion coefficient (ADC) of the optic nerves. White matter fiber bundle tracking was used to display optic nerves. RESULTS: Visual acuity was improved in 1 of the 6 patients after surgery. The mean FA of the injured eye declined significantly with regard to that of the normal eye (0.2438 ± 0.0670 vs. 0.4524 ± 0.0531; t = 8. 711; p = 0. 000). The mean ADC on the injured side increased significantly compared with that on the normal side [(1.4172 ± 0.1208) × 10(-3) mm(2)/s vs. (1.0866 ± 0.1179) × 10(-3) mm(2)/s; t = -5.316; p = 0. 003). The continuity of the intracanalicular segment of the optic nerve was interrupted in 3 patients without improved postoperative visual acuity. In 1 patient with improved postoperative visual acuity, the fiber bundle of the optic nerve was somewhat less dense in the injured eye than in the normal eye. CONCLUSIONS: DT-MRI provides valuable information for evaluating the fibers of optic nerves in TON.


Subject(s)
Diffusion Tensor Imaging/methods , Optic Nerve Injuries/pathology , Optic Nerve/pathology , Preoperative Care/methods , Visual Pathways/pathology , Adolescent , Adult , Anisotropy , Decompression, Surgical , Humans , Male , Nerve Fibers, Myelinated/pathology , Optic Nerve/surgery , Optic Nerve Injuries/surgery , Pilot Projects , Recovery of Function , Visual Pathways/surgery , Young Adult
20.
World Allergy Organ J ; 14(6): 100552, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34178240

ABSTRACT

BACKGROUND: A higher compliance with clinical guidelines helps improve treatment outcomes. But the clinical practice of otolaryngologists is not always consistent with guidelines. OBJECTIVE: To describe otolaryngologists' compliance with guidelines about allergic rhinitis (AR) management and identify factors responsible for the discordance between clinical practice and guideline recommendations in China. METHODS: A cross-sectional nationwide survey was designed and conducted via an online platform. Recruitment was done by emailing otolaryngologists registered in the Chinese Society of Otorhinolaryngology-Head and Neck Surgery or by inviting otolaryngologists to scan a Quick Respond (QR) code that linked to the questionnaire at various academic meetings. RESULTS: A total of 2142 otolaryngologists were eligible and completed the survey. Of them, 64.7% had over 10 years work experience and 97.4% had a bachelor's degree or higher. About 18.3% of the participants strictly copied the guideline in clinical practice, while 73.7% used the guideline that had been adjusted according to their clinical experience. Otolaryngologists were most concerned about the efficacy, safety, and minimum age of AR medications, and least concerned about patient preferences. Regarding the use of intranasal steroids (INS), leukotriene receptor antagonists (LTRA), and H1-antihistamines, 86.8%, 55.7% and 51.2% of otolaryngologists complied with the guideline recommendations, respectively. Educational background was a factor affecting the compliance with guidelines and acceptance of INS. CONCLUSION: A vast majority of Chinese otolaryngologists complied with the current Chinese AR guidelines. A difference still existed between the otolaryngologists' real-world and guideline-recommended management. The otolaryngologists should pay more attention to patient preferences. A higher education could improve otolaryngologists' adherence to the guidelines.

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