Prediction of rhinitis with class imbalance based on heterogeneous ensemble learning.

Common clinical rhinitis is characterized by different types of cases and class imbalance. Its prediction belongs to multiple output classification. Low recognition rate and poor generalization performance often occur for minority class. Therefore, we propose a novel integrated classification model, ARF-OOBEE, which transforms the multi-output classification to multi-label classification and multi-class classification. The multi-label classifier automatically adjusts the number and depth of integrated forest learners according to the imbalance ratio of single class label in a subset. It can effectively reduce the impact of class imbalance on classification and improve prediction performance of both majority or minority class concurrently. Also, we build a multi-class classification based on out-of-bag Extra-Tree to accomplish finer classification for the predicted labels. In addition, we calculate the feature importance for rhinitis on the grounds of the purity of nodes in decision-making tree inside Random Forest and study the correlation between rhinitis features. We conduct 12 folds cross-validation experiments on 461 cases of clinical rhinitis. The outcomes show that the evaluation indicators of ARF-OOBEE, such as Sensitivity, Specificity, Accuracy, F1-Score, AUC, and G-Mean are 74.9%,86.5%,92.0%,78.3%,95.3%, and 79.9%, respectively. In comparison to the other methods, ARF-OOBEE has better evaluation indicator and is more effective for the early clinical diagnosis of rhinitis.

Non-oxidized and oxidized flaxseed orbitides differently induce HepG2 cell apoptosis: involvement of cellular uptake and membrane death receptor DR4.

BACKGROUND: Flaxseed orbitides have health-promoting properties, particularly potent anti-cancer activity. However, flaxseed orbitides containing a methionine structure, such as [1-9-NαC]-linusorb B2 (CLB), are easily oxidized to sulfoxide ([1-9-NαC],[1-Rs,Ss-MetO]-linusorb-B2 (CLC)) and sulfone ([1-9-NαC], [1-MetO]-linusorb B2 (CLK)), with CLC having less anti-cancer ability than CLB. It is unclear why oxidized flaxseed orbitides are less effective against cancer than non-oxidized flaxseed orbitide. RESULTS: Non-oxidized ([1-9-NαC]-linusorb-B3 (CLA) and CLB) and oxidized (CLC and CLK) flaxseed orbitides were found to significantly upregulate the levels of pro-apoptotic proteins, including Bax/Bcl-2, CytoC, caspase-3, and caspase-8, in a dose-dependent manner, with non-oxidized flaxseed orbitides being more effective than oxidized flaxseed orbitides. Mechanically, the cellular absorption of non-oxidized flaxseed orbitides was higher than that of oxidized flaxseed orbitides. Moreover, the significant fluorescence quenching of DR4 protein by flaxseed orbitides (especially non-oxidized orbitides) indicated the formation of a DR4-orbitide complex. Molecular docking demonstrated that non-oxidized orbitides could easily dock into the active cavity of DR4 protein. Further blocking DR4 significantly reduced the ability of non-oxidized flaxseed orbitides to stimulate caspase-3 expression, whereas oxidized flaxseed orbitides retained this ability. CONCLUSION: Non-oxidized flaxseed orbitides are more effective against cancer than oxidized flaxseed orbitides due to higher cellular uptake and activation of the DR4-mediated death receptor signaling pathway. © 2024 Society of Chemical Industry.

Tissue-Resident Memory T Cells in Allergy.

Tissue-resident memory T (TRM) cells constitute a distinct subset within the memory T cell population, serving as the vanguard against invading pathogens and antigens in peripheral non-lymphoid tissues, including the respiratory tract, intestines, and skin. Notably, TRM cells adapt to the specific microenvironment of each tissue, predominantly maintaining a sessile state with distinctive phenotypic and functional attributes. Their role is to ensure continuous immunological surveillance and protection. Recent findings have highlighted the pivotal contribution of TRM cells to the modulation of adaptive immune responses in allergic disorders such as allergic rhinitis, asthma, and dermatitis. A comprehensive understanding of the involvement of TRM cells in allergic diseases bears profound implications for allergy prevention and treatment. This review comprehensively explores the phenotypic characteristics, developmental mechanisms, and functional roles of TRM cells, focusing on their intricate relationship with allergic diseases.

Application of nasal irrigation in the treatment of chronic rhinosinusitis.

Nasal irrigation (NI) for the local treatment of chronic rhinosinusitis (CRS) has some specificity due to the deep anatomical site of the sinuses. The purpose of this review is to help standardize the application of NI in healthcare practice, improve the prevention and treatment of CRS, and facilitate further research on the local treatment of CRS in the future. We searched the PubMed database for 342 articles in the last decade, using the keywords "saline nasal irrigation" and "chronic rhinosinusitis." We summarize the studies on the mechanism of action, rinsing solution, rinsing apparatus, and rinsing method of NI for CRS. NI plays an important role in the treatment of CRS, and it is a beneficial low-risk treatment. Isotonic saline is the most accepted flushing solution, and large-volume low-pressure flushing bottles are the flushing devices with the best flushing effect and are generally tolerated by patients. Phage, colloidal silver, and hydrogen can be further studied as components of rinses. NI plays an important role in the treatment of CRS, and it is a beneficial low-risk treatment. Further high-quality and expanded sample size studies on other flushing solutions, flushing head position, flushing frequency, and treatment courses are still needed, and lessons learned in practice.

Extracellular vesicles from adipose stem cells ameliorate allergic rhinitis in mice by immunomodulatory.

Background: Human adipose tissue-derived stem cells (hADSCs) exert potent immunosuppressive effects in the allogeneic transplantation treatment. In mouse model of allergic rhinitis (AR), ADSCs partially ameliorated AR. However, no study has evaluated the potential therapeutic effects of hADSC-derived extracellular vesicles (hADSC-EVs) on AR. Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce AR. One day after the last nasal drop, each group received phosphate buffered saline (PBS) or hADSC-EVs treatment. Associated symptoms and biological changes were then assessed. Results: hADSC-EV treatment significantly alleviated nasal symptoms, and reduced inflammatory infiltration. Serum levels of OVA-specific IgE, interleukin (IL)-4 and interferon (IFN)-γ were all significantly reduced. The mRNA levels of IL-4 and IFN-γ in the spleen also changed accordingly. The T helper (Th)1/Th2 cell ratio increased. The treatment efficacy index of hADSC-EV was higher than that of all human-derived MSCs in published reports on MSC treatment of AR. ADSC-EVs exhibited a greater therapeutic index in most measures when compared to our previous treatment involving ADSCs. Conclusion: These results demonstrated that hADSC-EVs could ameliorate the symptoms of AR by modulating cytokine secretion and Th1/Th2 cell balance. hADSC-EVs could potentially be a viable therapeutic strategy for AR. Further animal studies are needed to elucidate the underlying mechanisms and to optimize potential clinical protocols.

[The correlation between FCER2 gene polymorphism and the efficacy of inhaled corticosteroids in patients with chronic rhinosinusitis].

Objective:To investigate the correlation between FCER2（2206A>G） gene polymorphism and the efficacy of inhaled corticosteroids（ICS） in patients with chronic rhinosinusitis（CRS）. Methods:A total of 208 CRS patients were routinely treated with functional endonasal sinus surgery and postoperative ICS. DNA extraction, PCR amplification and gene sequencing were performed to observe the FCER2（2206A>G） gene polymorphism and calculate the allele frequency. The visual analog scale（VAS） score, Lund-Kennedy score, and computed tomography（CT） Lund-Mackay score were determined 6 months after surgery among patients with different genotypes. Moreover, the polymorphism frequency was compared among different subgroups（chronic rhinosinusitis with nasal polyps versus chronic rhinosinusitis without nasal polyps, eosinophilic chronic rhinosinusitis versus non-eosinophilic chronic rhinosinusitis）. Results:There were FCER2（2206A>G） gene polymorphism in patients with CRS, and the phenotypes included 3 genotypes, AA, AG and GG, with distribution frequencies of 68（32.7%）, 116（55.8%） and 24（11.5%） cases, respectively. No significant differences were found in age, VAS score, nasal endoscopic Lund-Kennedy score and CT imaging Lund-Mackay score among patients with CRS of each genotype before surgery. In patients with the AA genotype, the changes in VAS score（5.74±1.10）, Lund Kennedy score（5.92 ± 1.14）, and CT imaging Lund-Mackay score（13.26±4.26） were significantly higher than in patients with the AG（4.37±0.86, 5.37±1.24, 10.82±3.77） and GG（4.26±0.80, 5.18±1.56, 10.10±3.53） genotype（P<0.05）. However, there were no marked difference between patients with the AG genotype and those with the GG genotype（P>0.05）. Compared with patients with non-eosinophilic sinusitis, Among them, the differences between the GG genotype and AG /AA genes were more significant in eosinophilic sinusitis compared to non-eosinophilic sinusitis（P<0.01）. Conclusion:The FCER2（2206A>G） gene in patients with CRS has genetic polymorphism and is associated with the recovery of CRS patients after surgery, individual corticosteroid sensitivity, and subgroup variability.

LEF1 enhances ß-catenin transactivation through IDR-dependent liquid-liquid phase separation.

Wnt/ß-catenin signaling plays a crucial role in cancer development, primarily activated by ß-catenin forming a transcription complex with LEF/TCF in the nucleus and initiating the transcription of Wnt target genes. Here, we report that LEF1, a member of the LEF/TCF family, can form intrinsically disordered region (IDR)-dependent condensates with ß-catenin both in vivo and in vitro, which is required for ß-catenin-dependent transcription. Notably, LEF1 with disrupted IDR lost its promoting activity on tumor proliferation and metastasis, which can be restored by substituting with FUS IDR. Our findings provide new insight into the essential role of liquid-liquid phase separation in Wnt/ß-catenin signaling and present a potential new target for cancer therapy.

Comprehensive analysis of mitophagy-related genes in diagnosis and heterogeneous endothelial cells in chronic rhinosinusitis: based on bulk and single-cell RNA sequencing data.

Background: Chronic rhinosinusitis (CRS) is a complex inflammatory disorder affecting the nasal and paranasal sinuses. Mitophagy, the process of selective mitochondrial degradation via autophagy, is crucial for maintaining cellular balance. However, the role of mitophagy in CRS is not well-studied. This research aims to examine the role of mitophagy-related genes (MRGs) in CRS, with a particular focus on the heterogeneity of endothelial cells (ECs). Methods: We employed both bulk and single-cell RNA sequencing data to investigate the role of MRGs in CRS. We compiled a combined database of 92 CRS samples and 35 healthy control samples from the Gene Expression Omnibus (GEO) database and we explored the differential expression of MRGs between them. A logistic regression model was built based on seven key genes identified through Random Forests and Support Vector Machines - Recursive Feature Elimination (SVM-RFE). Consensus cluster analysis was used to categorize CRS patients based on MRG expression patterns and weighted gene co-expression network analysis (WGCNA) was performed to find modules of highly correlated genes of the different clusters. Single-cell RNA sequencing data was utilized to analyze MRGs and EC heterogeneity in CRS. Results: Seven hub genes-SQSTM1, SRC, UBA52, MFN2, UBC, RPS27A, and ATG12-showed differential expression between two groups. A diagnostic model based on hub genes showed excellent prognostic accuracy. A strong positive correlation was found between the seven hub MRGs and resting dendritic cells, while a significant negative correlation was observed with mast cells and CD8+ T cells. CRS could be divided into two subclusters based on MRG expression patterns. WGCNA analysis identified modules of highly correlated genes of these two different subclusters. At the single-cell level, two types of venous ECs with different MRG scores were identified, suggesting their varying roles in CRS pathogenesis, especially in the non-eosinophilic CRS subtype. Conclusion: Our comprehensive study of CRS reveals the significant role of MRGs and underscores the heterogeneity of ECs. We highlighted the importance of Migration Inhibitory Factor (MIF) and TGFb pathways in mediating the effects of mitophagy, particularly the MIF. Overall, our findings enhance the understanding of mitophagy in CRS, providing a foundation for future research and potential therapeutic developments.

Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.

Background: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Findings: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. Interpretation: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. Funding: KeyMed Biosciences (Chengdu) Limited.

Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. METHODS: The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment. RESULTS: GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1. CONCLUSION: Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.

Research Progress of Hydrogen on Chronic Nasal Inflammation.

Chronic nasal mucosal inflammatory disease is a common nasal disease, which is involved by inflammatory cells and a variety of cytokines. Its main pathological features are inflammatory reaction, increased secretion, mucosal swelling and thickening of nasal cavity or paranasal sinuses.It mainly includes chronic rhinitis (divided into allergic rhinitis, non-allergic rhinitis), chronic sinusitis (divided into with nasal polyps, without nasal polyps type), etc.The main symptoms of chronic rhinitis are nasal itching, sneezing, runny nose, and nasal congestion. The main symptoms of chronic sinusitis are nasal congestion, purulent or sticky nasal discharge, headache, and reduced sense of smell. They are a type of disease with a high incidence rate and seriously affect the quality of human life.Although the etiology and treatment of this type of disease have been extensively studied, there are still many aspects that are unclear.Currently, oxidative stress is believed to be an important link in the pathogenesis of chronic inflammatory diseases of the nasal mucosa. Therefore, anti-oxidative stress is a direction of research for the treatment of chronic nasal mucosal inflammatory diseases.Hydrogen, as a medically therapeutic gas, has been extensively studied for its antioxidant, anti-inflammatory, and anti-damage properties, and has been used in the treatment of various diseases.Although there are relatively few studies on the use of hydrogen for nasal inflammation, its positive effects have also been found. This article systematically summarizes the relevant research on the use of hydrogen to improve chronic nasal mucosal inflammation, with the aim of clarifying the ideas and indicating the direction for further research in the future.

[Association between airborne particulate matter（PM 2.5） concentration and the incidence of allergic rhinitis in Shanghai].

Objective:To explore the impact of PM 2.5 concentration in Shanghai on the incidence of allergic rhinitis（AR） in the population, and provide strategies for early warning and prevention of AR. Methods:Collect daily average concentrations of atmospheric pollutants monitored in Shanghai from January 1, 2017 to December 31, 2019, and clinical data of AR patients from five hospitals in Shanghai during the same period. We used a time-series analysis additive Poisson regression model to analyze the correlation between PM 2.5 levels and outpatient attendance for AR patients. Results:During the study period, a total of 56 500 AR patients were included, and the daily average concentration of PM 2.5 was（35.28±23.07）µg/m³. There is a correlation between the concentration of PM 2.5 and the number of outpatient attendance for AR cases. There is a positive correlation between the daily average number of outpatient for AR and levels of PM 2.5 air pollution（（P<0.05）） . We found that every 10 µg/m³ increase in PM 2.5, the impact of on the number of AR visits was statistically significant on the same day, the first day behind, and the second day behind, with the strongest impact being the exposure on the same day. Every 10 µg/m³ increases in PM 2.5, the number of outpatient visits increased by 0.526% on the same day（95%CI 1.000 50-1.010 04）. Conclusion:The atmospheric PM 2.5 concentration in Shanghai is positively correlated with the number of outpatient for AR, and PM 2.5 exposure is an independent factor in the onset of AR. This provides an important theoretical basis for AR.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

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.

Significance of Exhaled Nitric Oxide and Carbon Monoxide in Auxiliary Diagnosis and Evaluation of Allergic Rhinitis.

Objective: The concentration of exhaled NO and CO is considered as a candidate marker of respiratory inflammatory disease. This report discusses the exhaled NO and CO in the auxiliary diagnosis and evaluation of allergic rhinitis (AR). Methods: 60 AR patients from October 2017 to March 2019, compared with 30 healthy controls. The severity of AR disease was distinguished by symptom score. Both groups were tested for exhaled nitric oxide through the nose or mouth and exhale carbon monoxide through the mouth. AR patients received glucocorticoid nasal spray for 1 month and were tested again for nNO, eNO, eCO, and symptom score. Results: Before treatment, all the nNO, eNO, and eCO of the AR group were higher than the control group. There were differences in the severe and moderate subgroup: severe > moderate > mild. eCO was not significantly different between the mild and control groups. The nNO, eNO, and eCO levels were positively correlated with symptom score. After treatment, nNO decreased significantly in the three subgroups; eNO and eCO in the severe AR group decreased significantly. Drawing the ROC curve, the area under curve (AUC) of nNO is 0.978. The AUC of eNO and eCO was 0.786 and 0.577, respectively. Conclusion: The nNO, eNO, and eCO in the AR group are higher than healthy people, which positively correlated with the severity of AR symptoms. The detection of nNO, eNO, and eCO can monitor the changes of AR. The detection of nNO level as an indicator of AR auxiliary diagnosis has high accuracy.

Roles of regulatory B cells in the pathogenesis of allergic rhinitis.

Allergic rhinitis (AR) is a common otolaryngologic disease with frequent episodes of sneezing, clear nasal discharge flow and nasal congestion. The mechanisms of AR are complex and considered generally caused by the immune tolerance deficiency. Regulatory B cells (Bregs) are immunosuppressive cells that can modulate immune responses by the secretion of IL-10, IL-35, and tumor growth factor-ß (TGF-ß) and via the interaction of membrane surface molecules. However, Bregs are numerically deficient and/or dysfunctional in airway allergic diseases such as AR and allergic asthma, and the related mechanisms remain unclear. In this review, we summarize the role of Bregs in AR pathogenesis and highlight the importance of Bregs in maintaining immune tolerance. It is believed that further research on Bregs will contribute to developing new treatments and finding specific biomarkers that could help to predict disease progression.

The Beneficial Effects of Hydrogen-Rich Saline Irrigation on Chronic Rhinitis: A Randomized, Double-Blind Clinical Trial.

Purpose: Chronic rhinitis (CR) is a common chronic inflammation of the nasal mucosa. Nasal saline irrigation has been demonstrated to be an effective treatment for CR. In this study, we investigated the beneficial effects of hydrogen-rich saline irrigation as an anti-inflammatory irrigation therapy for CR and compared its effectiveness over saline irrigation. Hydrogen-rich saline (HRS) was investigated due to its antioxidant and anti-inflammatory properties. Methods: A total of 120 patients with CR were randomly divided into two groups, patients irrigated with HR (HRS group) and the control group irrigated with saline (NS group). A randomized, double-blind control study was performed. The main observation index in this study was the total score of nasal symptoms (TNSS). In addition, eosinophilic protein (ECP) of the nasal secretions, nasal nitric oxide (nNO) levels, and levels of regulatory T cells (Treg) and regulatory B cells (Breg) were also compared between the two groups. Furthermore, patients with allergic rhinitis (AR) and non-allergic rhinitis (NAR) were also evaluated based on serum-specific IgE positivity. Results: After treatment, TNSS and nasal ECP in the two groups decreased significantly (P<0.05), with patients in the HRS group showing significantly lower levels compared to the NS group (P<0.05). There were no significant differences in Treg and Breg levels between the two groups. Subgroup analysis showed that TNSS in the AR-HRS group showed a more significant reduction compared to the AR-NS group (P<0.05); however, there were no significant differences for the other inflammatory biomarkers (P>0.05). ECP levels were reduced significantly in the NAR subgroup compared to NS irrigation (P<0.05). There were no obvious adverse events observed in patients during the entire treatment period. Conclusion: Compared to saline irrigation, HRS nasal irrigation was found to improve CR clinical symptoms, especially in patients with AR. HRS could effectively be used for the clinical treatment of patients with CR.

Patterns of Caudate Lobe Invasion of Hilar Cholangiocarcinoma: A Panoramic Histologic Study of Liver.

BACKGROUND: At present, caudate lobectomy (CL) in hilar cholangiocarcinoma (HCCA) was controversial. Our study was designed to investigate the features of caudate lobe invasion (CLI) by whole-mount histologic large sections (WHLS). METHODS: A total of 46 HCCA patients underwent hemihepatectomy or trisectionectomy combined with CL were included. Serial WHLS (120 mm × 100 mm) were collected, and the relationship between caudate lobe and tumor was retained to determine the incidence of CLI. Hematoxylin and eosin (HE) and immunohistochemical (IHC) staining were completed to further explore the pathway of CLI. RESULTS: The whole region of the Glisson system in caudate lobe and hilar area can be clearly displayed by WHLS, and 32 (32/46 69.6%) patients were identified with CLI. There were three different pathways of CLI with panoramic IHC staining. The most common pathway is through the fibrous connective tissue along Glisson system (20/32 62.5%, without carcinoma in bile ducts). The Bismuth type, tumor size, vascular invasion, pathological type, and hepatic invasion were related to the CLI (p < 0.05). CONCLUSIONS: The incidence and distribution of CLI provided histologic evidence for CL in HCCA. Based on the invasion pathway, it is necessary to assess the fibrous connective tissue in Glisson system of caudate lobe in pathological research and practice.

Petrositis caused by fluconazole-resistant candida: case report and literature review.

BACKGROUND: Petrositis is a rare and fatal complication associated with otitis media. It is most likely caused by bacterial infections, but in some cases it is caused by fungal infections. CASE STUDY: The case in this report is associated with fungal petrositis. The clinical symptoms are: ear pain from chronic otitis media, severe headache, peripheral facial palsy and diplopia. The case was finally confirmed through imaging of middle ear, bacterial culture, pathology, and blood Metagenomic next-generation sequencing (mNGS) test. The patient was treated with sensitive antifungal drugs. CONCLUSION: Drug treatment is conservative but efficient method in this case. mNGS can provide pathogenic reference, when antibiotic is not efficient enough for fungal infections or drug-resistant fungal infections cases. This allows we to adjust drug use for the treatment.