Deep learning radiomics-based preoperative prediction of recurrence in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is characterized by poor prognosis and propensity for recurrence even after surgery. Identification of those CRS patients with high risk of relapse preoperatively will contribute to personalized treatment recommendations. In this paper, we proposed a multi-task deep learning network for sinus segmentation and CRS recurrence prediction simultaneously to develop and validate a deep learning radiomics-based nomogram for preoperatively predicting recurrence in CRS patients who needed surgical treatment. 265 paranasal sinuses computed tomography (CT) images of CRS from two independent medical centers were analyzed to build and test models. The sinus segmentation model achieved good segmentation results. Furthermore, the nomogram combining a deep learning signature and clinical factors also showed excellent recurrence prediction ability for CRS. Our study not only facilitates a technique for sinus segmentation but also provides a noninvasive method for preoperatively predicting recurrence in patients with CRS.

Transcriptomic analysis of asthma and allergic rhinitis reveals CST1 as a biomarker of unified airways.

Background: Allergic rhinitis (AR) is an important risk factor for the development of asthma. The "unified airway" theory considers the upper and lower airways as a morphological and functional whole. However, studies exploring biomarkers linking the upper and lower airways in allergic disease are lacking, which may provide insight into the mechanisms underlying AR comorbid asthma. Purpose: To integrate bioinformatics techniques to explore biomarkers in airway allergic diseases, and to provide a molecular etiology profile for preventing the development of asthma in AR patients. Methods: Biomarkers were screened by identifying key genes common between AR and asthma through WGCNA and differential gene analysis. GO and KEGG analyses were performed using DAVID. Immuno-infiltration analysis was performed by CIBERSORTx. The predictive value of CST1 to distinguish Th2-high asthma was determined by ROC curves. GSEA was used to analyze the signaling pathways involved in CST1. TargetScan and miRNet were combined with GSE142237 to construct ceRNA network. CMap was used to explore potential therapeutic drugs. Results: Validation of datasets showed that CST1 was the only gene that was up-regulated in both upper and lower airways in patients with AR and asthma, and correlation heatmaps showed that CST1 was the gene with the highest sum of correlation coefficients. GO and KEGG analysis demonstrated that the lower airways of AR patients were mainly involved in inflammatory and immune responses, similar to asthma. Immune infiltration showed that CST1 was mainly positively correlated with activated CD4 memory T cells. According to the ROC curve, CST1 showed excellent diagnostic efficiency for Th2-high asthma. GSEA indicated that CST1 was involved in the FcϵRI signaling pathway and O-glycan biosynthesis. A ceRNA network including the lncRNAs KCNQ1OT1 and NEAT1 was constructed. Four drugs, including verrucarin-A, had the potential to prevent the development of asthma in AR patients. In addition, corticosteroids were found to downregulate CST1 expression. Conclusion: CST1 plays a key role in the development of AR comorbid asthma and may be a biomarker for airway allergic diseases. Targeted treatment of CST1 has the potential to prevent the development of asthma in AR patients and deserves further study.

Plumbagin rescues the granulosa cell's pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome.

The survival of ovary granulosa cells (GC) is critical in the initiation and progression of polycystic ovary syndrome (PCOS) in females. Here, we found that the PCOS process is accompanied by massive GC pyroptosis resulting from Caspase-1 inflammasome activation. Administration of plumbagin, an effective compound isolated from plant medicine, can prevent the pyroptosis of GC and the onset of PCOS. Mechanistic study indicates the over-activation of the inflammasome in GC is due to the upregulation of WTAP, a key regulator of the RNA N6-methylase complex. WTAP mediates the mRNA N6-methylation of NLRP3 inflammasome component ASC and enhances ASC RNA stability, which results in the overactivation of the inflammasome in GCs from the PCOS model. Plumbagin treatment suppresses the WTAP-mediated N6-methylation of ASC mRNA and reduces the pyroptosis of GCs. This study supports the profound potential of plumbagin in PCOS treatment.

Over-expression of CRTH2 indicates eosinophilic inflammation and poor prognosis in recurrent nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by recurrent nasal polyp (NP) growth following surgical removal, but the mechanisms are still not clear. This study aimed to investigate the expression of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor on NP and the role it plays in eosinophil inflammation and polyp recurrence. Methods: Forty-one CRSwNPs patients and seventeen controls were enrolled in this study. mRNA was extracted from nasal tissues and evaluated for expression of CRTH2. Immunofluorescence staining was performed to confirm the distribution and expression of CRTH2 protein. CRTH2 expression on peripheral blood eosinophils was quantified by flow cytometry. The eosinophil count and clinical implications were also evaluated and their correlations with CRTH2 expression were analyzed. Results: Nasal polyps displayed increased expression of CRTH2 in mRNA level compared with control samples, with the highest expression observed in recurrent NP. Immunofluorescence confirmed over-expression of CRTH2 in recurrent NP and this was independent of the concurrent presence of asthma. CRTH2 expression was positively correlated with tissue eosinophil number (Spearman's ρ=0.69, P<0.001) and the postoperative sino-nasal outcome test-22 (SNOT-22) score (Spearman's ρ=0.67, P<0.001). Receiver operating characteristic (ROC) curves revealed CRTH2 was more predictive for NP recurrence compared to either eosinophil number and concomitant asthma, with an area under the ROC curve of 0.9107. Conclusion: The over-expression of CRTH2 in recurrent nasal polyps correlates with greater eosinophilic inflammation and poor prognosis which is independent of concomitant asthma.

Identification of key genes and pathways in chronic rhinosinusitis with nasal polyps and asthma comorbidity using bioinformatics approaches.

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma comorbidity (ACRSwNP) present severe symptoms and are more likely to relapse. However, the pathogenesis of ACRSwNP is not fully understood. The aim of this study was to explore the underlying pathogenesis of ACRSwNP using bioinformatics approaches. ACRSwNP-related differentially expressed genes (DEGs) were identified by the analysis of the GSE23552 dataset. The clusterProfiler R package was used to carry out functional and pathway enrichment analysis. A protein-protein interaction (PPI) network was built using the STRING database to explore key genes in the pathogenesis of ACRSwNP. The bioinformatics analysis results were verified through qRT-PCR. The Connectivity Map (CMap) database was used to predict potential drugs for the treatment of ACRSwNP. A total of 36 DEGs were identified, which were mainly enriched in terms of regulation of immune response and detection sensory perception of taste. Thirteen hub genes including AZGP1, AQP9, GAPT, PIP, and PRR4 were identified as potential hub genes in ACRSwNP from the PPI network. Analysis of the GSE41861 dataset showed that upregulation of CST1 in nasal mucosa was associated with asthma. qRT-PCR detection confirmed the bioinformatics analysis results. Tacrolimus and spaglumic acid were identified as potential drugs for the treatment of ACRSwNP from the CMap database. The findings of this study provide insights into the pathogenesis of ACRSwNP and may provide a basis for the discovery of effective therapeutic modalities for ACRSwNP.

Improvement of Subjective Olfactory Dysfunction in Chronic Rhinosinusitis With Nasal Polyps After Endoscopic Sinus Surgery.

Objective: Olfactory impairment is a common complaint in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), but the influence of endoscopic sinus surgery (ESS) on olfaction and the factors predicting olfactory impairment are not fully understood. This study aimed to assess the effect of ESS on improving olfactory dysfunction in patients with CRSwNP and to identify factors that predict prognosis. Methods: A total of 56 patients with CRSwNP reported their self-evaluated olfactory dysfunction score preoperatively and 1 month, 3 months, and 12 months after ESS. Preoperative clinical characteristics, computed tomography (CT) scan, and sinonasal endoscopy examination results were collected before surgery. Additionally, factors that predicted olfactory loss and affected the improvement of olfaction after ESS were evaluated. Results: Olfactory improvement can be observed 1 month after ESS. A total of 73.2% (41/56) subjects experienced sustained recovery of subjective olfaction with the self-evaluated olfactory dysfunction score improving from 2.04 to 0.64 (P < 0.001) after 12 months. The Lund-Mackay scores (r = 0.593, P < 0.001) and Lund-Kennedy scores (r = 0.265, P < 0.05) correlated with the preoperative olfactory dysfunction score. Multivariate logistic regression analysis revealed that longer duration of olfactory dysfunction, blood eosinophilia, lower Lund-Mackay scores, and peripheral distribution of CT opacification were risk factors that adversely affected the recovery of olfactory function (P < 0.05). Conclusion: ESS improved self-evaluated olfactory function in patients with CRSwNP. Lund-Mackay scores and Lund-Kennedy scores were correlated with olfactory function prior to surgery, while a longer course of the disease, higher blood eosinophilia, lower Lund-Mackay scores, and peripheral distribution of CT opacification were risk factors for poor olfactory prognosis.

Vision improvement in indirect traumatic optic neuropathy treated by endoscopic transnasal optic canal decompression.

BACKGROUND: Indirect Traumatic optic neuropathy (ITON) is a severe disease characterized by a sudden decline of visual function after craniofacial injury. However, the best treatment for ITON is unknown. Endoscopic transnasal optic canal decompression (ETOCD) has gradually been used for ITON treatment worldwide in recent years. OBJECTIVE: To assess the effect of ETOCD on visual acuity in patients with ITON and identify factors that affect prognosis. METHODS: In this study, clinical characteristics of 44 ITON patients who underwent ETOCD in Qilu Hospital of Shandong University were retrospectively analyzed. Factors affecting prognosis were also evaluated. RESULTS: ETOCD treatment improved the vision of 20 (45.5%) patients with no patient suffering from vision deterioration. The mean value of visual acuity (VA) scores improved from 1.57 to 2.39 (P < 0.001). Patients with residual vision had a better VA improvement percent than those without light perception (66.67% versus 34.48%, χ2 = 4.13, P = 0.042). Although shorter duration before ETOCD was associated with better improvement score in ITON patients (r = -0.30, P = 0.044), optic canal fracture (OCF) and optic nerve sheath incision did not affect the prognosis of these patients. Five ITON patients with cerebrospinal fluid rhinorrhea were treated with free nasal mucosal flap during the surgery, and no other severe surgical complication occurred. CONCLUSIONS: ETOCD can effectively and safely improve the vision of ITON patients, patients with residual vision and those treated earlier may benefit more from this surgery.

Plumbagin inhibits proliferation and promotes apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inactivating PI3K/Akt/mTOR pathway.

Polycystic ovary syndrome (PCOS) is recognized as a general endocrine disease and reproductive disorder. Although evidence indicates that PCOS has a complex etiology and genetic basis, the pathogenic mechanisms and signal pathway in PCOS remain unclear. In this study, the normal structure of follicle and corpus luteum were observed, and no cyst nor hyperemia was observed under the light microscopic study with hematoxylin and eosin (H&E) staining. Eestosterone and progesterone were evaluated by radioimmunoassay in rat serum. The alterations of proliferative ability and cell cycle distribution of each group were assessed by Cell Counting Kit-8 (CCK8) assay and flow cytometry. The protein expression of p-mTOR/mTOR, p-PI3K/PI3K, p-AKT/AKT, and GAPDH were analyzed by western blotting. Both doses of PLB could benefit the ovarian morphology and polycystic property. PLBinduced a suppress effect on the proliferation of rat ovarian granulosa cells. In addition, PLB also induced concentration-dependent apoptosis in rat ovarian granulosa cells. The rat ovarian granulosa cells treated with PLB that the expression levels of p-AKT, p-mTOR, and p-PI3K were significantly decreased in a concentration-dependent manner. PLB not only plays a critical role in attenuating the pathology and polycystic property changes in the ovary but can also induce rat ovarian granulosa cell apoptosis through the PI3K/Akt/mTOR signal pathway. This study showed the innovative role of PLB in the pathogenesis of PCOS and provides a new therapeutic modality for the treatment of PCOS.