Predictive modeling for eosinophilic chronic rhinosinusitis: Nomogram and four machine learning approaches.

Eosinophilic chronic rhinosinusitis (ECRS) is a distinct subset of chronic rhinosinusitis characterized by heightened eosinophilic infiltration and increased symptom severity, often resisting standard treatments. Traditional diagnosis requires invasive histological evaluation. This study aims to develop predictive models for ECRS based on patient clinical parameters, eliminating the need for invasive biopsy. Utilizing logistic regression with lasso regularization, random forest (RF), gradient-boosted decision tree (GBDT), and deep neural network (DNN), we trained models on common clinical data. The predictive performance was evaluated using metrics such as area under the curve (AUC) for receiver operator characteristics, decision curves, and feature ranking analysis. In a cohort of 437 eligible patients, the models identified peripheral blood eosinophil ratio, absolute peripheral blood eosinophil, and the ethmoidal/maxillary sinus density ratio (E/M) on computed tomography as crucial predictors for ECRS. This predictive model offers a valuable tool for identifying ECRS without resorting to histological biopsy, enhancing clinical decision-making.

Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis.

AIMS: To evaluate the impact of a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide (TZP), and its potential dose-response effect, on heart rate. METHODS: Articles were searched from PubMed, Web of Science, Embase, Cochrane Library, and clinical trials registries (ClinicalTrials.gov) databases. Randomized controlled trials (RCTs) comparing TZP at doses of 5, 10 and 15 mg in adults with type 2 diabetes were included. Six study arms were summarized from original research (TZP 5, 10 and 15 mg, GLP-1 receptor agonists [GLP-1RAs], insulin, placebo). The GLP-1RA and non-GLP-1RA groups were combined to form a control group. Two reviewers independently extracted data and assessed the quality of each study. Mean differences (MDs) were calculated as effect estimates for continuous outcomes. Pairwise meta-analyses and network meta-analyses were conducted. The study protocol was prospectively registered (PROSPERO ID: CRD42023418551). RESULTS: Eight articles were included in this systematic review and meta-analysis. The mean baseline heart rate ranged from 65.2 to 75.7 beats per minute. Pairwise meta-analysis showed that, compared with combined the control group, there were significantly greater increases in heart rates in the TZP group (MD 1.82, 95% confidence interval [CI] 0.75, 2.89). Similar significant rises were identified when comparing TZP with GLP-1RAs and non-GLP-1RAs (GLP-1 RAs: MD 2.29, 95% CI 1.00, 3.59; non-GLP-1RAs: MD 1.58, 95% CI 0.26, 2.91). TZP 5 mg was associated with smaller increases in heart rates compared to TZP 10 mg and TZP 15 mg (TZP 10 mg: MD -0.97, 95% CI -1.79, -0.14; TZP 15 mg: MD -2.57, 95% CI -3.79, -1.35). TZP 10 mg increased heart rate less than TZP 15 mg (MD -1.5, 95% CI -2.38, -0.82). Network meta-analysis indicated that TZP 15 mg was associated with significant increases in heart rate compared with TZP 5 mg (MD 2.53, 95% CI 1.43, 3.62), TZP 10 mg (MD 1.44, 95% CI 0.35, 2.53), GLP-1RAs (MD 3.46, 95% CI 1.67, 5.25), insulin (MD 2.86, 95% CI 1.32, 4.41) and placebo (MD 2.96, 95% CI 1.36, 4.57). CONCLUSIONS: Our study showed not only that there was a greater increase in heart rate in the TZP group than in the control, GLP-1RA and non-GLP-1RA groups, but also that the 15-mg dose of TZP had the strongest impact on increasing heart rates compared with the other five inventions, with a TZP dose-response impact on heart rate. Further research on the effects of TZP treatment-related increases in heart rate is required.

[The expression and significance of Piezo1 in chronic rhinosinusitis with nasal polyps].

Objective:To explore the expression and importance of Piezo1, E-cadherin, and Vimentin in nasal polyps patients. Methods:Thirty-five patients undergoing endoscopic sinus surgery under general anesthesia were streamed into 20 cases of nasal polyps（NP group） and 15 cases of simple septoplasty without any sinus disease（Control group）. Immunofluorescence staining and Western Blot were applied to detect the protein level of Piezo1, E-cadherin, and Vimentin in NP tissues and nasal polyp-derived primary human nasal epithelial cells（pHNECs）. Also, BEAS-2B cell lines were treated with human TGF-ß1 protein to establish epithelial mesenchymal transition（EMT） model in vitro and quantitative real-time polymerase chain reaction were used to calculate Piezo1 and above biomarkers in the model. Results:Compared with control group, Piezo1 and Vimentin showed higher level while E-cadherin was lower in NP tissues and pHNECs.In EMT model in vitro, Piezo1 and Vimentin were demonstrated higher expression with decreased level of E-cadherin. Conclusion:The tendency of Piezo1 is consistent with the mesenchymal-related biomarker Vimentin, going against with epithelial-related biomarker E-cadherin, implying its involvement with EMT process in nasal polyps.

An augmented Mendelian randomization approach provides causality of brain imaging features on complex traits in a single biobank-scale dataset.

Mendelian randomization (MR) is an effective approach for revealing causal risk factors that underpin complex traits and diseases. While MR has been more widely applied under two-sample settings, it is more promising to be used in one single large cohort given the rise of biobank-scale datasets that simultaneously contain genotype data, brain imaging data, and matched complex traits from the same individual. However, most existing multivariable MR methods have been developed for two-sample setting or a small number of exposures. In this study, we introduce a one-sample multivariable MR method based on partial least squares and Lasso regression (MR-PL). MR-PL is capable of considering the correlation among exposures (e.g., brain imaging features) when the number of exposures is extremely upscaled, while also correcting for winner's curse bias. We performed extensive and systematic simulations, and demonstrated the robustness and reliability of our method. Comprehensive simulations confirmed that MR-PL can generate more precise causal estimates with lower false positive rates than alternative approaches. Finally, we applied MR-PL to the datasets from UK Biobank to reveal the causal effects of 36 white matter tracts on 180 complex traits, and showed putative white matter tracts that are implicated in smoking, blood vascular function-related traits, and eating behaviors.

Methylated tumor suppressor gene SCARA5 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma.

Background: SCARA5 may play an important role in nasopharyngeal carcinoma. Materials & methods: PCR and immunohistochemistry were used to detect the expression and promoter methylation of SCARA5. Cell proliferation assays, spheroid culture, flow cytometry analysis, Transwell assays and xenotransplantation tests were utilized to determine the functional effects of SCARA5. RNA-sequencing, western blotting, immunofluorescence and dual-luciferase reporter assays were used to assess SCARA5-mediated outcomes. Results: SCARA5 was downregulated by promoter methylation. Overexpression of SCARA5 inhibited cell migration, invasion and proliferation. SCARA5 enhanced nasopharyngeal carcinoma cell sensitivity to chemotherapy with cisplatin and 5-fluorouracil. SCARA5 drives tumor apoptosis by downregulating HSPA2. Conclusion: SCARA5 may be a useful clinical marker in nasopharyngeal carcinoma.

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.

YES-associated protein-regulated Smad7 worsen epithelial barrier injury of chronic sinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) was potentially due to the epithelial barrier injury. YES-associated protein (YAP) is a multifunctional transcriptional factor and plays versatile roles in the regulation and maintenance of epithelial barrier in different organs and tissues. The purpose of this study is to elucidate possible effect and mechanism of YAP on the epithelial barrier of CRSwNP. METHODS: Patients were divided into CRSwNP group (n = 12) and control group (n = 9). The location of YAP, PDZ-binding transcriptional co-activator (TAZ), and Smad7 were estimated by immunohistochemistry and immunofluorescence. Meanwhile, the expression of YAP, TAZ, Zona occludens-1 (ZO-1), E-cadherin, and transforming growth factor-beta1 (TGF-ß1) were detected by Western blot. After primary human nasal epithelial cells were treated with YAP inhibitor, the expression level of YAP, TAZ, ZO-1, E-cadherin, TGF-ß1, and Smad7 were measured by Western blot. RESULTS: Compared with the control group, the protein levels of YAP, TAZ, and Smad7 were significantly upregulated, while TGF-ß1, ZO-1, and E-cadherin were downregulated in CRSwNP. YAP and Smad7 demonstrated lower levels, while the expression of ZO-1, E-cadherin, and TGF-ß1 rose slightly after YAP inhibitor treatment in primary nasal epithelial cells. CONCLUSIONS: Higher level of YAP may lead to CRSwNP epithelial barrier injury via the TGF-ß1 signaling pathway, and the inhibition of YAP can partially reverse epithelial barrier function.

The development of nasal polyps involves early middle meatus mucous remodeling via TGF-β1 mediated PAI-1 reduction

Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.

Roles of Anatomical Abnormalities in Localized and Diffuse Chronic Rhinosinusitis.

Background: This study aimed to examine the roles of anatomical variation in localized and diffuse chronic rhinosinusitis [LCRS and DCRS]) . Methods: A database was analyzed retrospectively on patients hospitalized in the Department of Otorhinolaryngology of our university hospital from 2017 to 2020. A total of 281 patients were included and divided into three categories: patients with LCRS, patients with DCRS, and a normal control group. The frequency of anatomical variation, the demographic information, disease type (with or without polyps), symptom visual analogue scale (VAS) scores and Lund-Mackay (L-M) scores were calculated and compared. Results: Anatomical variants were observed more frequently in LCRS than DCRS (P < 0.05). The frequency of variation was higher in the LCRSwNP group than the DCRSwNP group (P < 0.05), and higher in the LCRSsNP group than the DCRSsNP group (P < 0.05). The L-M scores for patients with DCRS with nasal polyps were significantly higher (14.96 ± 6.15) than those of patients with DCRS without nasal polyps (6.80 ± 5.00) and also significantly higher (3.78 ± 2.07) than those of patients with LCRS with nasal polyps (2.63 ± 1.12; P < 0.05). A poor correlation was observed between the severity of symptoms and the performance of CT scans in CRS (R = 0.29, P < 0.01). Conclusion: Anatomical variants were common in CRS, and possibly correlated with LCRS but not with DCRS. The frequency of anatomical variation is not associated with the occurrence of polyps. CT could reflect the severity of disease symptoms to some extent.

Early detection and serial monitoring during chemotherapy-radiation therapy: Using T1 and T2 mapping cardiac magnetic resonance imaging.

Purpose: To confirm the ability of native T1 and T2 values in detecting and monitoring early myocardial injuries of chest radiotherapy in neoplasm patients. Materials and methods: Fifteen participants received non-anthracycline chemotherapy and chest radiotherapy, and 30 age/gender-matched controls were enrolled in this prospective study. Cardiac magnetic resonance scans were performed within 2 days, 3 months, and 6 months after chest radiotherapy. Myocardial native T1 and T2 values were measured in irradiated and nonirradiated areas. Meanwhile, the parameters of left ventricular function and left ventricular myocardial strain were obtained. Results: There were no significant differences in left ventricular function, native T1, T2, and strain between patients and controls before chest radiotherapy. In 15 participants who were followed up for 6 months, there was a significant change only in left ventricular ejection fraction (LVEF) among baseline and the first follow-up (P = 0.021), while the adjusted P-value was higher than 0.05 after Bonferroni correction, as well as other parameters. Native T1 values were elevated at 3 and 6 months in irradiated areas compared with baseline (1,288.72 ± 66.59 ms vs. 1,212.51 ± 45.41 ms; 1,348.01 ± 54.16 ms vs. 1,212.51 ± 45.41 ms; P < 0.001 for both). However, T2 values only changed at 3 months in irradiated areas compared with baseline (44.21 ± 3.35 ms vs. 39.14 ± 1.44 ms; P = 0.006). Neither the native T1 nor T2 values changed in nonirradiated areas during the follow-up period (all P > 0.05). There were no significant differences in strain changes during the follow-up period (all P > 0.05). Conclusion: Native T1 and T2 values elevated at 3 months after chest radiotherapy, whereas LVEF showed no significant change during the 6-month follow-up.

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.

The development of nasal polyps involves early middle meatus mucous remodeling via TGF-ß1 mediated PAI-1 reduction.

OBJECTIVE: Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. METHODS: Samples were streamed as early Nasal Polyps (eNP, n=10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n=14), and Control group (n=15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-ß1 (Transforming Growth Factor-beta 1) activator, TGF-ß1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. RESULTS: The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-ß1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-ß1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-ß1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. CONCLUSION: Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-ß1-mediated PAI-1 reduction. LEVEL OF EVIDENCE: 3b.

HER2-positive breast cancer progresses rapidly after pyrotinib resistance: acquired RET gene fusion and TP53 gene mutation are potential reasons.

Approximately 15-20% of the patients with breast cancer overexpress human epidermal growth factor receptor 2 ( HER2 ). HER2 -positive breast cancer is highly aggressive and has a high relapse rate, suggesting that it is prone to and progresses rapidly after drug resistance. Pyrotinib resistance and changes in patients' conditions after drug resistance are challenging clinical issues and require medical attention. Recently, there are few clinical reports on changes in patients' conditions after pyrotinib resistance. We report a case of a 46-year-old patient with HER2 -positive breast cancer who developed resistance to pyrotinib and rapidly progressed to uncontrolled liver failure in less than a week. To elucidate the cause of the rapid progression, we collected samples of the patient's ascites and performed next-generation sequencing (NGS). On the basis of the NGS results, we speculated that the rapid progression after pyrotinib resistance might be due to RET gene fusion and TP53 gene mutations. Therefore, this case report aims to alert oncologists that patients with HER2 -positive breast cancer, who are resistant to pyrotinib or other targeted drugs, could experience rapid or even flare-up progression and that RET gene fusion and TP53 gene mutations might be potential causes.

Local Immunoglobulin E in nasal polyps: Role and modulation.

In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE's characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen- Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-ß, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.

Serum amyloid protein (SAA) as a healthy marker for immune function in Tridacna crocea.

Serum amyloid protein (SAA) is known as an acute reactive protein of innate immunity in mammals. However, in invertebrates, the role of SAA in innate immunity is still unclear. In this study, a full-length cDNA of the SAA gene (named TcSAA) was cloned from Tridacna crocea, mollusca. The gene includes a 193 bp 5' untranslated region (UTR) and a 129 bp 3' UTR sequence, and the open reading frame (ORF) with 393 bp nucleotides encodes a polypeptide of 130 amino acids. TcSAA contains a typical signal peptide and an SAA functional domain. The mRNA expression of TcSAA was detected in all 12 selected tissues and 7 different developmental stages. Furthermore, the expression of TcSAA was increased quickly in hemocytes after challenge with V. coralliilyticus or LPS. Furthermore, rTcSAA could bind V. coralliilyticus and V. alginolyticus, and the protein could reduce the lethality rate of the clams from 80% to 55% which caused by V. coralliilyticus about 48 h after injection. In summary, these results indicate that TcSAA may act as a marker for monitoring health and protecting T. crocea.

Short report: nasal obstruction recovery after septoplasty in patients with nasal septal deviation affected by anxiety and depression.

This research was aimed to explore whether the recovery of subjective symptoms and objective examination in nasal septum deviation (NSD) patients after septoplasty were related to the degree of preoperative anxiety or depression, in the hope of providing new ideas for clinical treatment. A total of 150 NSD patients were included in this prospective research. Visual analogue scale (VAS) scores, Nasal Obstruction Symptom Evaluation (NOSE) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, total inspiratory and expiratory nasal resistance were recorded before and 6 months after operation. The results showed preoperative anxiety or depression was not statistically different between groups in terms of age, gender and course, but positively correlated with nasal obstruction (VAS and NOSE). The recovery of nasal obstruction in patients with anxiety or depression was worse than that in normal NSD patients 6 months after surgery, and was decreased with the increase of anxiety or depression degree. And no significant difference showed in the reduction of total inspiratory and expiratory nasal resistance between groups. In conclusion, anxiety and depression affected the improvement of nasal obstruction feeling in NSD patients after septoplasty, and the improvement was negatively correlated with the degree of anxiety and depression. It is necessary to evaluate the anxiety and depression of NSD patients before septoplasty.

MDM2 is involved in the regulation of p53 expression in the immune response of oyster Crassostrea hongkongensis.

MDM2 (mouse double-minute) and p53 form a negative feedback loop and play a prominent role in preventing the induction of uncontrolled apoptosis. To better understand their potential roles in oyster Crassostrea hongkongensis, MDM2 and p53 homologs were first isolated and cloned in C. hongkongensis (named ChMDM2 and Chp53), and their mRNA expression patterns in tissues and developmental stages were analyzed. Multiple sequence alignment analysis and phylogenetic analysis of ChMDM2 and Chp53 displayed a high degree of homology and conservation. In addition, exposure to Vibrio coralliilyticus resulted in DNA damage and apoptosis in the hemocytes of C. hongkongensis, and found that the mRNA expression level of ChMDM2 was decreased, while the relative expression of Chp53 was significantly increased in the hemocytes and gills. Furthermore, fluorescence from ChMDM2-EGFP and Chp53-Red were found to be distributed in the nucleus of HEK293T cells. Besides, dual-luciferase reporter assays showed that ChMDM2 antagonized with Chp53 and participates in p53 signaling pathway. In addition, the interaction between ChMDM2 and Chp53 was confirmed strongly by Co-immunoprecipitation assays. Furthermore, the results of RNAi showed that ChMDM2 and Chp53 participated in apoptosis which induced infection of V. coralliilyticus. Taken together, our results characterized the features of ChMDM2 and Chp53, which played a critical role in apoptosis of C. hongkongensis.

Inhibition of MicroRNA miR-101-3p on prostate cancer progression by regulating Cullin 4B (CUL4B) and PI3K/AKT/mTOR signaling pathways.

To probe into the efffects of miR-101-3p via regulating CUL4B within PI3K/AKT/mTOR signaling pathway on progression of prostate cancer (PCA). Western blot and qRT-PCR were adopted to detect CUL4B and miR-101-3p expressions in 75 cases with PCA . The cellular strains of PCA (LNCaP and PC3) were chose as the objects to check the targeting correlation between CUL4B and miR-101-3p through dual-luciferase reporter experiments. LNCaP cells and PC3 cells were randomly divided into the blank group, miR-101-3p mimic group, siRNA negative control (NC) group, CUL4B siRNA group and CUL4B siRNA plus the miR-101-3p inhibitor group. Cellular bioactivity measurement was done via Cell-Light EDU, MTT, Annexin-V-FITC/PI, scratch-heal experiments and invasion tests of Transwell. MiR-101-3p expression was decreased more signally in tumor tissues than in normal tissues adjacent to the cancer. MiR-101-3p inhibited cellular proliferating, migrating and invasion. Nevertheless, it promoted cellular apoptosis, up-regulated apoptotic proteins as well as down-regulated anti-apoptotic proteins. CUL4B siRNA and miR-101-3p simulation were similar in terms of their outcomes. Nonetheless, these results could be reversed through the miR-101-3p inhibitor. Besides, CUL4B siRNA and the simulation halted a serious of PI3K signal in PCA cells. MiR-101-3p expression was down-regulated in PCA patients. CUL4B was upregulated in PCA patients. Moreover, miR-101-3p suppressed cellular invasion, migration, proliferation and led to cellular apoptosis, which might be related to the PI3K/AKT/mTOR signaling pathway suppression. Finally, we found, MiR-101-3P suppressed PCA progression via aiming for CUL4B, which may offer the new molecular target for PCA clinical treatment.

A nationwide survey of otolaryngologists' compliance with Chinese guidelines for diagnosis and treatment of allergic rhinitis.

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.