Molecular determinants of olfactory receptor activation: Comparative analysis of Olfr205 and Olfr740 family member responses to indole.

Indole is widely present in nature and contributes significantly to the smell of flowers and animal excretion. However, the odor perception mechanism for indole is unclear, despite previous reports suggesting that it activates the Olfr740 family of receptors. In this study, we successfully identified another receptor, Olfr205, that is responsive to indole. Molecular model construction and binding pocket analysis predicted that the A202 residue in transmembrane helix 5 of Olfr205 forms a crucial hydrogen bond with indole, facilitating receptor activation. Additionally, G112 in transmembrane helix 3 of the Olfr740 family is involved in indole activation of receptors. Finally, our mutant function assay showed that substitution of A202 in Olfr205 and G112 in Olfr740 with other amino acids significantly decreased the receptor response to indole, which provides robust evidence to confirm the docking results. In summary, our study is the first to reveal that Olfr205 is an olfactory receptor distinct from those in the Olfr740 family that is activated by indole. Moreover, these receptors display different indole-binding mechanisms. This study sheds light on molecular binding mechanisms and contributes to a deeper understanding of indole perception.

TMEM59 ablation leads to loss of olfactory sensory neurons and impairs olfactory functions via interaction with inflammation.

The olfactory epithelium undergoes constant neurogenesis throughout life in mammals. Several factors including key signaling pathways and inflammatory microenvironment regulate the maintenance and regeneration of the olfactory epithelium. In this study, we identify TMEM59 (also known as DCF1) as a critical regulator to the epithelial maintenance and regeneration. Single-cell RNA-Seq data show downregulation of TMEM59 in multiple epithelial cell lineages with aging. Ablation of TMEM59 leads to apparent alteration at the transcriptional level, including genes associated with olfactory transduction and inflammatory/immune response. These differentially expressed genes are key components belonging to several signaling pathways, such as NF-κB, chemokine, etc. TMEM59 deletion impairs olfactory functions, attenuates proliferation, causes loss of both mature and immature olfactory sensory neurons, and promotes infiltration of inflammatory cells, macrophages, microglia cells and neutrophils into the olfactory epithelium and lamina propria. TMEM59 deletion deteriorates regeneration of the olfactory epithelium after injury, with significant reduction in the number of proliferative cells, immature and mature sensory neurons, accompanied by the increasing number of inflammatory cells and macrophages. Anti-inflammation by dexamethasone recovers neuronal generation and olfactory functions in the TMEM59-KO animals, suggesting the correlation between TMEM59 and inflammation in regulating the epithelial maintenance. Collectively, TMEM59 regulates olfactory functions, as well as neuronal generation in the olfactory epithelium via interaction with inflammation, suggesting a potential role in therapy against olfactory dysfunction associated with inflamm-aging.

Preoperative Transarterial Embolization of Advanced Juvenile Nasopharyngeal Angiofibroma Using n-Butyl Cyanoacrylate: Case-Control Comparison with Microspheres.

PURPOSE: To evaluate the efficacy and safety of transarterial embolization (TAE) with n-butyl cyanoacrylate (nBCA) for juvenile nasopharyngeal angiofibroma (JNA). MATERIALS AND METHODS: A retrospective review was performed on patients with JNA who underwent TAE and endoscopic resection between 2020 and 2022. Patients embolized with nBCA were identified, and those embolized with microspheres were set as the control group. Data on demographics, symptoms, tumor characteristics, blood loss, adverse events, residual disease, and recurrence were collected, and case-control analysis was performed for the 2 groups. Differences in characteristics between the groups were tested using the Fisher exact and Wilcoxon tests. A generalized linear model (GLM) was used to analyze the univariate and multivariate influences on blood loss. RESULTS: Twenty patients were included in this study: 13 in the microsphere group and 7 in the nBCA group. The median blood loss was 400 mL (interquartile range [IQR], 200-520 mL) in the nBCA group and 1,000 mL (IQR, 500-1,000 mL) in the microsphere group (P = .028). The GLM confirmed lower blood loss in the nBCA group (relative risk, 0.58 [0.41-0.83]; P = .01). A residual tumor was found in 1 patient in each group (7.7% vs 14.3%; P = 1.000). Recurrence was not observed in any patient. None of the patients experienced adverse events during embolization. CONCLUSIONS: TAE of advanced JNA with nBCA glue is safe and effective and can significantly reduce intraoperative blood loss compared with microspheres.

Chitinase-Like Protein Ym2 (Chil4) Regulates Regeneration of the Olfactory Epithelium via Interaction with Inflammation.

The adult olfactory epithelium (OE) regenerates sensory neurons and nonsensory supporting cells from resident stem cells after injury. How supporting cells contribute to OE regeneration remains largely unknown. In this study, we elucidated a novel role of Ym2 (also known as Chil4 or Chi3l4), a chitinase-like protein expressed in supporting cells, in regulating regeneration of the injured OE in vivo in both male and female mice and cell proliferation/differentiation in OE colonies in vitro We found that Ym2 expression was enhanced in supporting cells after OE injury. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE, while Ym2 overexpression by lentiviral infection accelerated OE regeneration. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Furthermore, anti-inflammatory treatment reduced Ym2 expression and delayed OE regeneration in vivo and cell proliferation/differentiation in vitro, which were counteracted by Ym2 overexpression. Collectively, this study revealed a novel role of Ym2 in OE regeneration and cell proliferation/differentiation of OE colonies via interaction with inflammatory responses, providing new clues to the function of supporting cells in these processes.SIGNIFICANCE STATEMENT The mammalian olfactory epithelium (OE) is a unique neural tissue that regenerates sensory neurons and nonsensory supporting cells throughout life and postinjury. How supporting cells contribute to this process is not entirely understood. Here we report that OE injury causes upregulation of a chitinase-like protein, Ym2, in supporting cells, which facilitates OE regeneration. Moreover, anti-inflammatory treatment reduces Ym2 expression and delays OE regeneration, which are counteracted by Ym2 overexpression. This study reveals an important role of supporting cells in OE regeneration and provides a critical link between Ym2 and inflammation in this process.

Analysis of clinicopathologic features and expression of NR4A3 in sinonasal acinic cell carcinoma.

Acinic cell carcinoma (AiCC) in the nasal cavity and paranasal sinuses has rarely been reported in literature. A recent study demonstrated that recurrent genomic rearrangement [t(4;9) (q13;q31)] is a driver event in AiCC of the salivary glands that could promote the upregulation of transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). In the current study, we evaluated the clinicopathological characteristics and expression of NR4A3 in four new cases of sinonasal AiCC. All four patients were men (range, 27-70 years). The tumor involved only the nasal cavity in two patients, while the other two patients showed involvement of both the nasal cavity and ethmoid sinus. Histologically, the tumor displayed a predominantly solid growth pattern and was composed of hematoxyphilic serous-like cells and scattered intercalated duct-like cells. Immunohistochemically, all cases expressed DOG-1. However, staining for mammaglobin, S-100, CA9, and P63 was absent in all patients. All four cases showed positive nuclear staining for NR4A3. In contrast, none of the other 39 sinonasal tumors, including secretory carcinomas, pleomorphic adenomas, mucoepidermoid carcinomas, adenoid cystic carcinomas, renal cell-like adenocarcinomas, intestinal-type adenocarcinomas, non-intestinal-type adenocarcinomas, extraskeletal myxoid chondrosarcoma, and carcinoma ex pleomorphic adenomas, presented with any positive NR4A3 nuclear staining. Additionally, NR4A3 rearrangements were observed in three cases with sinonasal AiCC by fluorescence in situ hybridization, and the expression level of NR4A3 mRNA was significantly increased in sinonasal AiCC compared with that in normal parotid tissue. Our study demonstrated that sinonasal AiCCs are characterized by an indolent nature and histopathological similarity to parotid AiCCs. Moreover, NR4A3 is a reliable biomarker for distinguishing sinonasal AiCCs from other sinonasal carcinomas.

Identification of key pseudogenes in nasopharyngeal carcinoma based on RNA-Seq analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and pseudogenes playing important roles in genesis of multiple tumor types is still not clear and needs to be investigated. METHODS: Using RNA-Sequencing (RNA-seq) technology, we analyzed pseudogene expression in 13 primary NPC and 6 recurrent NPC samples as well as their paracancerous counterparts. Quantitative PCR was used to validate the differentially expressed pseudogenes. RESULTS: We found 251 differentially expressed pseudogenes including 73 up-regulated and 178 down-regulated ones between primary NPC and paracancerous tissues. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted to filter out the key pseudogenes. We reported that pseudogenes from cytochrome P450 (CYP) family, such as CYP2F2P, CYP2G1P, CYP4F24P, CYP2B7P and CYP2G2P were significantly down-regulated in NPC compared to paracancerous tissues, while IGHV1OR15-2, IGHV3-11, FCGR1CP and IGHV3-69-1 belonging to Fc gamma receptors were significantly up-regulated. CYP2B7P, CYP2F2P and CYP4F26P were enriched in arachidonic acid metabolism pathway. The qRT-PCR analysis validated the lower expression of pseudogenes CYP2F2P and CYP2B7P in NPC tissues and cell lines compared to paracancerous tissues and normal human nasopharyngeal epithelial cell line. CYP2B7P overexpression weakened migratory and invasive capacity of NPC cell line. Moreover, the expression pattern of those pseudogenes in recurrent NPC tissues was different from the primary NPC. CONCLUSION: This study suggested the role of pseudogenes in tumorigenesis and progression, potentially functioning as therapeutic targets to NPC.

Assessment of Internal Carotid Artery Invasion With the Endoscopic Endonasal Approach: Implications of a New Grading System and Security Strategy.

BACKGROUND: Internal carotid artery (ICA) injury during the endoscopic endonasal approach (EEA) for ventral cranial base tumors is rare but fatal. OBJECTIVE: The aim of this study was to investigate the relationship between ventral cranial base tumors and corresponding ICA using quantitative means to improve the safety of surgery. MATERIAL AND METHODS: In this retrospective study, a total of 46 patients with ventral cranial base tumors undergoing surgery with the EEA were enrolled. Preoperative imaging features and clinical data were recorded. The influencing factors of the gross total resection (GTR) rate were analyzed. A new grading system and security strategy were developed. RESULTS: Postoperative enhanced magnetic resonance imaging showed a GTR of 61.7%. There was a significant correlation between the GTR rate and tumors surrounding the ICA, the tumor site, the involved ICA segment, and the blood supply (P < 0.05). We included preoperative radiotherapy as supplementary data in the grading system. Each variable involved the letter "S"; (surround, site, segment, blood supply, supplementary data); hence, the system was named the 5S ICA grading scale. CONCLUSION: We recommend a safety assessment through the 5S ICA grading scale and the ICA grading strategy to obtain the maximum total resection rate while ensuring patient safety.

Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts.

The fish olfactory receptor ORA family is orthologous to the mammalian vomeronasal receptors type 1. It consists of six highly conserved chemosensory receptors expected to be essential for survival and communication. We deorphanized the zebrafish ORA family in a heterologous cell system. The six receptors responded specifically to lithocholic acid (LCA) and closely related C24 5ß-bile acids/salts. LCA attracted zebrafish as strongly as food in behavioral tests, whereas the less potent cholanic acid elicited weaker attraction, consistent with the in vitro results. The ORA-ligand recognition patterns were probed with site-directed mutagenesis guided by in silico modeling. We revealed the receptors' structure-function relationship underlying their specificity and selectivity for these compounds. Bile acids/salts are putative fish semiochemicals or pheromones sensed by the olfactory system with high specificity. This work identified their receptors and provided the basis for probing the roles of ORAs and bile acids/salts in fish chemosensation.

Endoscopic transnasal transmaxillary approach to the upper parapharyngeal space and the skull base.

PURPOSE: Treatment of tumors arising in the upper parapharyngeal space (PPS) or the floor of the middle cranial fossa is challenging. This study aims to present anatomical landmarks for a combined endoscopic transnasal and anterior transmaxillary approach to the upper PPS and the floor of the middle cranial fossa and to further evaluate their clinical application. METHODS: Dissection of the upper PPS using a combined endoscopic endonasal transpterygoid and anterior transmaxillary approach was performed in six cadaveric heads. Surgical landmarks associated with the approach were defined. The defined approach was applied in patients with tumors involving the upper PPS. RESULTS: The medial pterygoid muscle, tensor veli palatini muscle and levator veli palatini muscle were key landmarks of the approach into the upper PPS. The lateral pterygoid plate, foramen ovale and mandibular nerve were important anatomical landmarks for exposing the parapharyngeal segment of the internal carotid artery through a combined endoscopic transnasal and anterior transmaxillary approach. The combined approach provided a better view of the upper PPS and middle skull base, allowing for effective bimanual techniques and bleeding control. Application of the anterior transmaxillary approach also provided a better view of the inferior limits of the upper PPS and facilitated control of the internal carotid artery. CONCLUSIONS: Improving the knowledge of the endoscopic anatomy of the upper PPS allowed us to achieve an optimal approach to tumors arising in the upper PPS. The combined endoscopic transnasal and anterior transmaxillary approach is a minimally invasive alternative approach to the upper PPS.

Notch Signaling Regulates Lgr5+ Olfactory Epithelium Progenitor/Stem Cell Turnover and Mediates Recovery of Lesioned Olfactory Epithelium in Mouse Model.

The Notch signaling pathway regulates stem cell proliferation and differentiation in multiple tissues and organs, and is required for tissue maintenance. However, the role of Notch in regulation of olfactory epithelium (OE) progenitor/stem cells to maintain tissue function is still not clear. A recent study reported that leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is expressed in globose basal cells (GBCs) localized in OE. Through lineage tracing in vivo, we found that Lgr5+ cells act as progenitor/stem cells in OE. The generation of daughter cells from Lgr5+ progenitor/stem cells is delicately regulated by the Notch signaling pathway, which not only controls the proliferation of Lgr5+ cells and their immediate progenies but also affects their subsequent terminal differentiation. In conditionally cultured OE organoids in vitro, inhibition of Notch signaling promotes neuronal differentiation. Besides, OE lesion through methimazole administration in mice induces generation of more Notch1+ cells in the horizontal basal cell (HBC) layer, and organoids derived from lesioned OE possesses more proliferative Notch1+ HBCs. In summary, we concluded that Notch signaling regulates Lgr5+ GBCs by controlling cellular proliferation and differentiation as well as maintaining epithelial cell homeostasis in normal OE. Meanwhile, Notch1 also marks HBCs in lesioned OE and Notch1+ HBCs are transiently present in OE after injury. This implies that Notch1+ cells in OE may have dual roles, functioning as GBCs in early development of OE and HBCs in restoring the lesioned OE. Stem Cells 2018;36:1259-1272.

The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb.

Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5+ cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP+ cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells.SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5+ cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons.

Effect of nebulized budesonide on decreasing the recurrence of allergic fungal rhinosinusitis.

OBJECTIVE: The aim of this study was to evaluate the clinical efficacy and the effects on decreasing the recurrence of AFRS (allergic fungal rhinosinusitis) of a budesonide inhalation suspension delivered via transnasal nebulization to patients following endoscopic sinus surgery. SUBJECTS AND METHODS: Thirty-five patients were recruited into this study. Final diagnoses were reached using Bent and Kuhn's criteria. The eligible patients were randomly divided into two groups: the budesonide transnasal nebulization group (group A) and the topical nasal steroids group (group B). Nasal symptoms, Lund-Mackay scores, and Kupferberg grades were evaluated before surgery, after surgery and during the follow-up to assess the effects of these two approaches. RESULTS: A total of 30 patients with AFRS who were eligible were included in the study. Four of the 15 patients in group B (26.67%) developed recurrent disease, whereas no patients in group A developed recurrent disease. This difference was statistically significant (p=0.032). CONCLUSION: Nebulized budesonide is an effective and safe treatment for patients with AFRS following endoscopic sinus surgery, as evidenced by the reduced recurrence rate observed in the budesonide transnasal nebulization group relative to the topical nasal steroids group.

Adenoid Cystic Carcinoma of the Nasopharynx: A Retrospective Study of 12 Cases.

Objective: This study aimed to describe the experience of a single institution in China in treating adenoid cystic carcinoma of the nasopharynx. Methods: We reviewed the previous literature and conducted a retrospective analysis of 12 patients who diagnosed with nasopharyngeal adenoid cystic carcinoma (NACC) in clinical data, treatment, and follow-up data during 2019 to 2021. Results: Patients ranged in age from 32 to 68 years (mean 40.7 years, median 48.5 years), with a male to female ratio of 5:7. Most of our patients have T4a and T4b diseases (50% and 25%, respectively). A quarter of patients develop distant metastases. Among the 12 patients, 7 of them have positive margins under the microscope (7/12, 58.3%). The chief clinical manifestations were epistaxis, facial swelling, facial pain, headache ear stuffy, and hearing loss. If the tumors involved with cavernous sinus, brain stem infiltrated, and internal carotid artery circumvented, patients will undertake routine enhanced magnetic resonance imaging with Magnetic Resonance Angiography/Magnetic Resonance Venogram (MRA/MRV) to clearly show the lesion region. All patients underwent endoscopic endonasal approach. Fifty percent of patients received radiotherapy and 25% of patients received chemotherapy. None of the patients was lost and the follow-up time ranged from 16 to 45 months. The mean and median follow-up were 2.08 and 1.58 years. Two patients were dead of distant metastasis within 18 and 20 months after the surgery, and another patient with recurrent NACC died of hemorrhage. Conclusion: NACC is a rare malignant tumor that occurs in the nasopharynx, which can grow along the nerve, destroy the bone of the skull base, and metastasize to other organs. Up to now, there is no standard treatment. Our results show that endoscopic sinus surgery is a better choice for advanced or recurrent NACC.

Blood eosinophilia and a higher ethmoid sinus/maxillary sinus score ratio predict new-onset asthma in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUD: Presently, the impact of Chronic rhinosinusitis with nasal polyps (CRSwNP) on asthma onset is unknown. AIMS: To evaluate the role of CRSwNP in asthma onset. MATERIALS AND METHODS: A total of 3107 CRSwNP patients were retrospectively screened from 1 January 2018, to 31 May 2021; 624 patients were enrolled. Clinical data regarding nasal symptoms, Lund-Mackay scores, blood eosinophil percentage, and onset of asthma were analyzed. Patients were divided into different groups according to past history of nasal polyps, Lund-Mackay score, and the extent of blood eosinophilia. Asthma-free rates between these subgroups were analyzed by Kaplan-Meier curves and Cox regression models. RESULTS: The prevalence of asthma was 10.90% in patients with CRSwNP, and new-onset asthma occurred in 3.14% of these patients. Higher Lund-Mackay scores for ethmoid sinus and maxillary sinus (E/M) and blood eosinophil percentages were two independent risk factors for new-onset asthma, with hazard ratios of 1.267 (95%CI, 1.155-1.390) and 1.224 (95%CI, 1.054-1.422), respectively. CRSwNP patients with an E/M ratio > 2.33 or a blood Eos percentage > 5.5% were at risk for asthma onset. CONCLUSIONS AND SIGNIFICANCE: Blood eosinophilia and a higher E/M score ratio were associated with new-onset asthma in patients with CRSwNP.

[Drafâ ¢ approach to unilateral frontal sinus for contralateral drainage].

Objective:Anatomical variation or scar atresia of the drainage channel of the frontal sinus on the affected side, and opening the frontal sinus through the drainage channel of the frontal sinus on the affected side may lead to surgical failure. The purpose of this study is to explore a modified Draf Ⅲ operation to complete the drainage of the affected frontal sinus by removing the floor wall and septum of the frontal sinus and connecting the bilateral frontal sinus through the healthy side of the frontal sinus. Methods:Through the anatomical study of 2 skull bone specimens and 2 fresh frozen specimens, the surgical landmark and surgical approach were explored. Four patients with frontal sinus atresia and frontal sinusitis after DrafⅡb surgery in Eye & ENT Hospital of Fudan University were retrospectively analyzed. Descriptive method was used to analyze the data. Results:The bottom wall of bilateral frontal sinus was removed, and the bilateral frontal sinus was enlarged above the nasal septum to form a large common cavity. The uncinate process and ethmoid bubble were retained, and the midline drainage of the affected frontal sinus in the healthy side of the nasal cavity was completed. From August 2022 to April 2023, 4 patients with frontal sinus atresia and frontal sinusitis after DrafⅡb surgery for unilateral frontal sinus papilloma in Eye & ENT Hospital of Fudan University were treated with surgery. The headache symptoms disappeared after surgery, and the drainage of frontal sinus was spacious, the mucosa healed well and the drainage was unobstructed under endoscopy. There were no other postoperative complications. Conclusion:DrafⅢ approach to unilateral frontal sinus for contralateral drainage can drain the affected frontal sinus adequately. The essence of this operation is to drain the bilateral frontal sinus in the unilateral nasal cavity, and this operation has short path, less trauma, and a broader prospect, which is suitable for promotion.

[Research progress in the anatomy and surgical approach of the parapharyngeal space].

The parapharyngeal space, a complex fascial compartment within the head and neck region, encompasses crucial anatomical structures including blood vessels and nerves. Tumors occurring within this space are rare, with the majority being benign in nature. Surgical intervention remains the primary treatment modality; however, managing parapharyngeal space tumors poses significant challenges due to their intricate anatomical configuration. Conventional open surgical approaches have been associated with significant tissue damage and a high prevalence of postoperative complications. Recently, advancements in anatomical studies and surgical techniques have led to significant progress in understanding parapharyngeal space anatomy and improving surgical management. This article aims to provide a comprehensive overview of these developments.

Anatomical studies and early results on endoscopic transoral medial pterygomandibular fold approach to salvage retropharyngeal lymphadenectomy in nasopharyngeal carcinoma.

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.

The IL-31/CysLT2R axis is associated with itching in patients with allergic rhinitis.

BACKGROUND: Itching is a troublesome symptom that disturbs patients with allergic rhinitis (AR). The molecular mechanisms underlying itching in AR need to be further illuminated. The aim of this study was to investigate the role of epithelial cell-derived interleukin-31 (IL-31) in nasal itching in AR. METHODS: A total of 33 patients and 20 healthy control subjects were enrolled in this prospective study. The disease severity of patients with AR was assessed by the total visual analog scale score. The levels of IL-31, cysteinyl leukotriene receptor 1 (CysLT1R), and CysLT2R in the nasal brush specimens from the enrolled subjects were measured by quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of CysLT2R in a human nasal epithelial cell line (HNEpC) was assessed by immunofluorescence staining. RESULTS: Compared with the control subjects, the protein and mRNA levels of IL-31 and CysLT2R were significantly increased in patients with AR. Higher levels of IL-31 and CysLT2R in nasal epithelial cells were associated with itching but not nasal congestion, rhinorrhea, or sneezing in AR. A significant relationship was found between IL-31 and CysLT2R in nasal epithelial cells, with a correlation coefficient of 0.93. Furthermore, RT-PCR and immunofluorescence staining revealed that IL-31 directly induced CysLT2R expression in HNEpCs. Nasal steroid treatment inhibited IL-31 and CysLT2R expression in 13 patients with AR in vivo. CONCLUSIONS: Nasal epithelial cell-derived IL-31 might be associated with itching symptoms via CysLT2R in AR.

Continuum robots for endoscopic sinus surgery: Recent advances, challenges, and prospects.

PURPOSE: Endoscopic sinus surgery (ESS) has been recognized as an effective treatment modality for paranasal sinus diseases. Over the past decade, continuum robots (CRs) for ESS have been studied, but there are still some challenges. This paper presents a review on the scientific studies of CRs for ESS. METHODS: Based on the analysis of the anatomical structure of the paranasal sinus, the requirements of CRs for ESS are discussed. Recent studies on rigid robots, handheld flexible robots, and CRs for ESS are presented. Surgical path planning, navigation, and control are also included. RESULTS: Concentric tube CRs and cable-driven CRs have great potential for applications in ESS. The CRs incorporated with multiple replaceable arms with different functions are preferable in ESS. CONCLUSION: Further study on navigation and control is required to improve the performance of CRs for ESS.