Objective: To analyze the recovery of olfactory function in patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery and to identify factors influencing recovery to provide a theoretical foundation for taking effective measures. Methods: This was a retrospective analysis included 277 CRSwNP patients with olfactory dysfunction who underwent endoscopic sinus surgery at the First Affiliated Hospital of Chongqing Medical University from October 2021 to September 2023. This study included 189 males and 88 females, with a median age of 46 years (range: 18-84 years). Routine laboratory tests, sinus CT Lund-Mackay score, modified sinus CT score, endoscopic polyp score, and nasal endoscopic Lund-Kennedy score were included for preoperative assessments. Eosinophil counts were obtained from nasal polyp tissues during surgery. The University of Pennsylvania smell identification test (UPSIT) was administered before surgery and 6 months after surgery to evaluate olfactory function. Based on results of postoperative olfactory test, patients were divided into two groups: the group with improved olfactory function and without improvement of olfactory function. Chi-square test and multivariate Logistic regression were used to analyze relevant factors affecting postoperative olfactory function of CRSwNP patients, and the prediction model was constructed to verify its consistency and to analyze its prediction efficiency. Results: Of the 277 patients, 155 (56%) showed improved olfactory function and 122 (44%) did not improve after surgery. Multivariate Logistic regression analysis identified following independent factors associated with improved postoperative olfactory function: concurrent allergic rhinitis (OR=2.34), long duration of olfactory dysfunction (OR=1.13), higher total score of CT olfactory zone (OR=1.26), higher Lund-Kennedy score (OR=1.23), presence of olfactory cleft polyps (OR=4.72), higher tissue eosinophil count (OR=1.01) and high IL-6 levels (OR=1.51). Conversely, a higher endoscopic polyp score (OR=0.74) was associated with a lower likelihood of olfactory improvement. The nomogram model, validated using receiver operating characteristic (ROC) analysis, demonstrated good clinical efficacy with an area under the curve (AUC) of 0.80 (95%CI: 0.748-0.852). The calibration curve showed an absolute error of 0.021, indicating good consistency and predictive accuracy. Conclusions: Factors such as a medical history of allergic rhinitis, duration of olfactory dysfunction, total score of sinus CT olfactory zone, endoscopic Lund-Kennedy score, olfactory cleft polyps, tissue eosinophil count, IL-6 level and endoscopic polyp score independently influence postoperative olfactory function of CRSwNP patients. The nomogram model based on these independent factors has good clinical efficacy, which can be used to predict the postoperative olfactory function in CRSwNP patients with olfactory dysfunction.
Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.
Abstract Objective While lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. Methods and Results We found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-κB subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-κB pathway activation in endothelial cells by TNF-α. We treated ApoE -/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE -/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. Conclusions Rhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-κB, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE -/- mice.
Literature has well-established the importance of 3- O -sulfation of neuronal cell surface glycan heparan sulfate (HS) to its interaction with herpes simplex virus type 1 glycoprotein D (gD). Previous investigations of gD to its viral receptors HVEM and nectin-1 also highlighted the conformational dynamics of gD’s N- and C-termini, necessary for viral membrane fusion. However, little is known on the structural interactions of gD with HS. Here, we present our findings on this interface from both the glycan and the protein perspective. We used C-terminal and N-terminal gD variants to probe the role of their respective regions in gD/HS binding. The N-terminal truncation mutants (with Δ1-22) demonstrate equivalent or stronger binding to heparin than their intact glycoproteins, indicating that the first 22 amino acids are disposable for heparin binding. Characterization of the conformational differences between C-terminal truncated mutants by sedimentation velocity analytical ultracentrifugation distinguished between the “open” and “closed” conformations of the glycoprotein D, highlighting the region’s modulation of receptor binding. From the glycan perspective, we investigated gD interacting with heparin, heparan sulfate, and other de-sulfated and chemically defined oligosaccharides using surface plasmon resonance and glycan microarray. The results show a strong preference of gD for 6- O -sulfate, with 2- O -sulfation becoming more important in the presence of 6- O -S. Additionally, 3- O -sulfation shifted the chain length preference of gD from longer chain to mid-chain length, reaffirming the sulfation site’s importance to the gD/HS interface. Our results shed new light on the molecular details of one of seven known protein-glycan interactions with 3- O -sulfated heparan sulfate.
Interleukin-17A (IL-17A) is a key inflammatory cytokine in many disorders, while the significance of IL-17A in nasal polyposis (NP) is still obscure. This study aimed to investigate the expression of IL-17A in nasal polyps from both atopic and nonatopic patients and its associations with clinical and histological features.In all, 30 patients with NP were included, and were grouped into atopic and nonatopic patients according to skin prick test (SPT). Disease severity was evaluated by symptom score, endoscopy score and CT score. Histological characteristics were assessed by eosinophilic infiltration, basement membrane (BM) thickness, epithelial damage, squamous metaplasia, and goblet cell hyperplasia. IL-17A expression in polyps was detected by ELISA and immunohistochemistry.Endoscopy score and CT score were significantly higher in atopic NP patients than in nonatopic NP patients (p < 0.05). IL-17A levels were significantly upregulated in both atopic (p < 0.01) and nonatopic (p < 0.05) patients versus controls. Furthermore, IL-17A levels were significantly higher in the atopic group versus nonatopic group. Significantly positive correlations were found between IL-17A levels and CT scores, eosinophilic infiltration and BM thicknesses.These results indicated that expression of IL-17A was significantly upregulated in NP patients and was more severe in atopic NP patients, suggesting that IL-17A may play an important role in the pathology of NP and atopy may contribute to NP by stimulating the production of IL-17A.
The application of solid-state (SS) nanopore devices to single-molecule nucleic acid sequencing has been challenging. Thus, the early successes in applying SS nanopore devices to the more difficult class of biopolymer, glycosaminoglycans (GAGs), have been surprising, motivating us to examine the potential use of an SS nanopore to analyze synthetic heparan sulfate GAG chains of controlled composition and sequence prepared through a promising, recently developed chemoenzymatic route. A minimal representation of the nanopore data, using only signal magnitude and duration, revealed, by eye and image recognition algorithms, clear differences between the signals generated by four synthetic GAGs. By subsequent machine learning, it was possible to determine disaccharide and even monosaccharide composition of these four synthetic GAGs using as few as 500 events, corresponding to a zeptomole of sample. These data suggest that ultrasensitive GAG analysis may be possible using SS nanopore detection and well-characterized molecular training sets.
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