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.

A deep weakly semi-supervised framework for endoscopic lesion segmentation.

In the field of medical image analysis, accurate lesion segmentation is beneficial for the subsequent clinical diagnosis and treatment planning. Currently, various deep learning-based methods have been proposed to deal with the segmentation task. Albeit achieving some promising performances, the fully-supervised learning approaches require pixel-level annotations for model training, which is tedious and time-consuming for experienced radiologists to collect. In this paper, we propose a weakly semi-supervised segmentation framework, called Point Segmentation Transformer (Point SEGTR). Particularly, the framework utilizes a small amount of fully-supervised data with pixel-level segmentation masks and a large amount of weakly-supervised data with point-level annotations (i.e., annotating a point inside each object) for network training, which largely reduces the demand of pixel-level annotations significantly. To fully exploit the pixel-level and point-level annotations, we propose two regularization terms, i.e., multi-point consistency and symmetric consistency, to boost the quality of pseudo labels, which are then adopted to train a student model for inference. Extensive experiments are conducted on three endoscopy datasets with different lesion structures and several body sites (e.g., colorectal and nasopharynx). Comprehensive experimental results finely substantiate the effectiveness and the generality of our proposed method, as well as its potential to loosen the requirements of pixel-level annotations, which is valuable for clinical applications.

Preoperative Embolization of Primary Juvenile Nasopharyngeal Angiofibroma: Is Embolization of Internal Carotid Artery Branches Necessary?

PURPOSE: To determine the effects of blood supply from internal carotid artery (ICA) on the surgical outcomes of primary juvenile nasopharyngeal angiofibroma (JNA) after transarterial embolization (TAE). METHODS: A retrospective analysis was performed on primary JNA patients who underwent TAE and endoscopic resection in our hospital between December 2020 and June 2022. The angiography images of these patients were reviewed, and then they were divided into ICA + external carotid artery (ECA) feeding group and ECA feeding group according to whether the ICA branches were part of the feeding arteries. Tumors in ICA + ECA feeding group were fed by both ICA and ECA branches, while tumors in ECA feeding group were fed by ECA branches alone. All patients underwent tumor resection immediately after ECA feeding branches embolization. None of the patients underwent ICA feeding branches embolization. Data on demographics, tumor characteristics, blood loss, adverse events, residual and recurrence were collected, and case-control analysis was performed for the two groups. Differences in characteristics between the groups were tested using Fisher's exact and Wilcoxon tests. RESULTS: Eighteen patients were included in this study: nine in ICA + ECA feeding group and nine in ECA feeding group. The median blood loss was 700 mL (IQR 550-1000 mL) in ICA + ECA feeding group versus 300 mL (IQR 200-1000 mL) in ECA feeding group, with no significant statistical difference (P = 0.306). Residual tumor was found in one patient (11.1%) in both groups. Recurrence was not observed in any patient. There were no adverse events from embolization and resection in either group. CONCLUSION: The results of this small series suggest that the presence of blood supply from ICA branches in primary JNA has no significant effect on intraoperative blood loss, adverse event, residual and postoperative recurrence. Therefore, we do not recommend routine preoperative embolization of ICA branches. LEVEL OF EVIDENCE: Level 4, Case-control.

Comparative short-term efficacy of endoscopic sinus surgery and biological therapies in chronic rhinosinusitis with nasal polyps: A network meta-analysis.

BACKGROUND: To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. METHODS: Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random-effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non-RCT design, and insufficient participants or follow-up were excluded. RESULTS: In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT-22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. CONCLUSIONS: In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head-to-head trials and real-world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP.

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.

[The outcome of transnasal endoscopic total maxillectomy in the treatment of sinonasal adenoid cystic carcinoma].

Objective:To assess the prognosis of sinonasal adenoid cystic carcinoma with hard palatine invasion treated by transnasal endoscopic total maxillectomy. Methods:Clinical data of twenty-six patients with sinonasal adenoid cystic carcinoma invading hard palatine treated by transnasal endoscopic total maxillectomy between May 2014 and December 2020 was analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Cox regression was used to investigate the prognosis factors. Masticatory function after maxillectomy has also been assessed using the questionnaire of patients' satisfaction about masticatory function. Results:Margins in 8 patients（30%） were positive. The median time of follow-up was 38 months（6 to 85 months）. Twenty-five patients recurred. Four patients died of distant metastasis. The 5-year overall survival rate and relapse-free survival rate was 79.5% and 89.1%, respectively. Independent predictors of outcome on multivariate analysis were positive margin（P=0.018）, recurrence（P=0.006） and distant metastasis（P=0.04）. Conclusion:Transnasal endoscopic total maxillectomy could be performed for the treatment of the sinonasal adenoid cystic carcinoma with hard palatine invasion. Positive margin, local recurrence and distant metastasis were important predictors for patients' prognosis.

Sinonasal intestinal- and non-intestinal-type adenocarcinoma in China: a retrospective study of 14 cases.

BACKGROUND: In China, reports on the epidemiology of adenocarcinomas of the nasal cavity and paranasal sinuses are limited. AIM: This study aimed to describe the experience of a single institution in China in treating these malignant tumours. MATERIALS AND METHODS: We conducted a retrospective chart review of patients with adenocarcinoma of the nasal cavity and paranasal sinuses admitted between January 2019 and December 2021. Tumour staging was based on the American Joint Committee on Cancer, 8th edition, for sinonasal malignancies. RESULTS: The series included 10 men and 4 women (mean age, 54.5 [range, 14-80] years). Epistaxis and nasal obstruction were the most common clinical manifestations in 10 (71.4%) patients. Ten (71.4%) had stage T4 disease at diagnosis, but no patient had lymph node or distant metastasis. The posterosuperior septum (100.0%) and middle turbinate (92.8%) were the two sites most vulnerable to tumour invasion. All patients underwent endoscopic resection as the initial treatment; one patient died. CONCLUSIONS AND SIGNIFICANCE: In China, these malignancies are related to exposure to certain substances; however, diagnosis can be delayed. Endoscopic resection is a suitable treatment option for adenocarcinomas of the nasal cavity and paranasal sinuses.

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.

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.

Endoscopic surgery is superior to intensity-modulated radiotherapy in the treatment of advanced recurrent nasopharyngeal carcinoma.

BACKGROUND: The choice between endoscopic surgery and re-radiotherapy as the main treatment modality in patients with advanced recurrent nasopharyngeal carcinoma (rNPC) remains controversial. Therefore, in this study, we compared the efficacies of endoscopic surgery and intensity-modulated radiotherapy (IMRT) in patients with rNPC. METHODS: All patients with advanced rNPC (T3 and T4) who underwent salvage treatment were enrolled from January 2009 to December 2020. Overall survival (OS) was analyzed using a log-rank analysis. Univariate and multivariate analyses of OS were performed using a Cox regression model. Common treatment-related complications of endoscopic surgery were compared with those of IMRT. RESULTS: The numbers of patients with T3 and T4 tumors were 163 (64.2%) and 91 (35.8%), respectively; 192 patients underwent endoscopic surgery, 51 received IMRT, and 11 received three-dimensional conformal radiotherapy (3D-CRT). The 3-year OS of patients treated with endoscopic surgery was 59.3%, which was significantly higher than that of patients treated with IMRT (34.7%, p < 0.001) or 3D-CRT (43.6%, p = 0.012). Multivariate analyses showed that IMRT was an independent risk factor for OS compared with endoscopic surgery (hazard ratio, 2.068; 95% confidence interval, 1.395-3.069, p < 0.001). Complications of aural fullness (p = 0.001), nasopharyngeal necrosis (p = 0.004), nasopharyngeal hemorrhage (p = 0.004), dysphagia (p < 0.001), and cerebral infarction (p = 0.030) were significantly lower in the endoscopic surgery group than in the IMRT group. CONCLUSION: Endoscopic surgery may be a more promising salvage treatment than IMRT to maximize survival and minimize treatment-related complications in advanced rNPC. These results will be significant in deciding the optimal treatment for patients with advanced rNPC.

Innovative Fudan rT staging in endoscopic surgery for recurrent nasopharyngeal carcinoma.

BACKGROUND: American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) rT staging have great clinical impracticality. The aim of the present study was to establish a new rT staging to guide endoscopic surgery for the treatment of recurrent nasopharyngeal carcinoma (rNPC). METHODS: This surgical rT staging (named Fudan rT staging) was constructed using two significant risk factors: the distance from the tumor margin to the internal carotid artery, and dural invasion. Log-rank and receiver operating characteristic (ROC) curve analyses were used to evaluate its effectiveness. RESULTS: Fudan rT staging can effectively separate the overall survival (OS) and progression-free survival (PFS) of patients with rNPC according to the different rT stages (p < 0.05). In addition, ROC analysis showed that the Fudan rT staging exhibited enhanced prognostic value for OS and PFS compared with the AJCC/UICC rT staging. CONCLUSIONS: The innovative Fudan rT staging has a better predictive value for the survival of patients with rNPC than AJCC/UICC rT staging.

Transoral robotic resection of advanced recurrent nasopharyngeal carcinoma involving the internal carotid artery.

BACKGROUND: Transoral robotic surgery (TORS) is a reliable, minimally invasive approach for treating recurrent nasopharyngeal carcinoma (rNPC). However, tumours involving the internal carotid artery (ICA) are considered to be unsuitable for TORS. This paper presents the first case of transoral robotic resection of advanced rNPC involving the ICA. MATERIALS AND METHODS: This case is a 55 year-old male patient who received radiotherapy 27 years ago. This patient underwent a standard TORS resection 2 weeks after ipsilateral ICA embolization. RESULTS: Postoperative Magnetic resonance imaging and biopsy results indicated total resection. During the 2 month follow-up, no severe complications were found, and the primary site was tumour-free. CONCLUSION: This study preliminarily presents the feasibility and efficiency of advanced rNPC resection with TORS. TORS can potentially provide better quality of life for patients as a less invasive approach than current endoscopic surgery. Even so, the surgical approach should be selected strictly according to the tumour's location.

A nomogram for predicting overall survival of patients with sinonasal melanoma: A population-based study.

Objective: Sinonasal melanoma (SMM) is a rare but aggressive malignancy with 5-year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SMM remain undefined. We aimed to establish a model to predict the survival outcomes of SMM. Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SMM between 1975 and 2016. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. We also developed and validated a nomogram for OS, and compared its performance with that of conventional staging systems. Results: Overall, 305 SMM patients were included in this population-based study. Multivariate Cox regression showed that primary site, American Joint Committee on Cancer stage, radiotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C-indices, areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis demonstrated reliable performance of the nomogram. Conclusion: The nomogram predicting survival outcomes of SMM patients based on clinical information showed good discriminative ability and prognostic accuracy compared with conventional stage classifications. Our nomogram could be used to predict the survival probabilities for SMM patients at different timepoints. Level of Evidence: 2b.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Lgr5+ cells are required and dynamically participate in olfactory epithelium regeneration: a revisiting shows Lgr5 expression in multiple cell lineages.

Olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) detect thousands of volatile environmental odors to form the sense of smell. OSNs are generated from basal cells, which show the characteristics of progenitor/stem cells. In the mammalian OE, persistent neurogenesis occurs during lifetime, providing a unique model to study the tissue turnover and fate determination of stem cells. Methods: Immunohistochemical analysis and RNAscope in situ hybridization indicated the localization of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) in the intact and injured OE. Lineage tracing was conducted to analyze the dynamic role of Lgr5+ cells in the OE homeostasis and regeneration. We also used DTR-driven genetic depletion of Lgr5+ cells and lentivirus-mediated Lgr5 downregulation to demonstrate the essential role of Lgr5+ cells in the OE regeneration. Results: We show that Lgr5 marks horizontal basal cells (HBCs) in the OE of adults but not newborns. We revisit the role of Lgr5+ cells in the OE homeostasis and regeneration, and find that Lgr5+ cells participate in the OE homeostasis from neonatal to one-month-old age, as well as in the OE regeneration post injury. During the OE regeneration, Lgr5 is transiently expressed in apical supporting cells, immature neurons, and mature sensory neurons. The Lgr5+ cells become or generate HBCs in the regenerated OE. DTR-driven cell depletion shows that Lgr5+ cells are not necessary in the adult OE homeostasis, but required in the recovery of OE from injury. Lgr5 down-regulation by lentiviral infection also demonstrates the essential role of Lgr5 expression in the OE regeneration. Conclusion: Our study elucidates the role of Lgr5+ cells in the OE homeostasis and regeneration, potentially providing a candidate to cell-based therapy against olfactory dysfunction.

[A vidian neurectomy approach with the sphenoid process of the palatine bone as a landmark].

Objective:To explore a safe and effective surgical approach to locate and cut the vidian nerves with the sphenoid process of the palatine bone as a landmark. Methods: The landmarks of locating the external opening of the vidian canal were confirmed by the dissection of the cadaveric heads, and the feasibility of locating the vidian nerves with the determined landmarks was verified during operation. Results:The anatomical landmarks, which are the anterior opening of palatovaginal canal, the posterior opening of palatovaginal canal, palatovaginal canal and the nasal pharyngeal crest of the root of the pterygoid process can be used as the important landmarks of locating vidian nerve. In the cases of 10 patients with refractory allergic rhinitis and vasomotor rhinitis, the vidian nerves were successfully located and sectioned, and one patient was complicated with short-term unilateral palatal numbness after surgery. Conclusion:The anterior opening of palatovaginal canal, the posterior opening of palatovaginal canal, palatovaginal canal and the nasal pharyngeal crest of the root of the pterygoid process can be used as surgical markers for vidian neurectomy with the sphenoid process of the palatine bone as landmarks.

[The application of submental flap in the nasopharyngectomy for nasopharyngeal carcinoma].

Objective:To explore the anatomy and clinical application of submental flap in the nasopharyngectomy for nasopharyngeal carcinoma. Methods:The anatomical study of the submental flap was carried out on 5 cadavers, focusing on exploring the channel of the submental flap transposition to the nasopharyngeal skull base area, and analyzing the nasopharyngeal skull base area covered by the submental flap. A retrospective analysis of 4 patients with submental flap repairment after nasopharyngectomy was performed, and the surgical methods and techniques of submental flap to repair nasopharyngeal nasal skull base defect were introduced in detail. Rusults: It showed that the submental flap could be transposed into the nasopharyngeal skull base through the posteromedial of the mandible-posterior pterygoid muscle-parapharyngeal space channel, and could cover the paraclival internal carotid artery. Clinical practice showed that the submental flap was successfully used to repair the nasopharyngeal skull base defect in 4 patients, and the submental flap grew well in the follow-up. Conclusion:The submental flap is suitable for the repair of the nasopharyngeal skull base defect after nasopharyngeal carcinoma surgery, and it is worthy of clinical promotion.

Transinfratemporal Fossa Transposition of the Temporalis Muscle Flap for Skull Base Reconstruction after Endoscopic Expanded Nasopharyngectomy: Anatomical Study and Clinical Application.

Objective Temporalis muscle flap (TMF) is widely used in traditional skull base surgery, but its application in endoscopic skull base surgery remains rarely reported. We aimed to investigate the surgical anatomy and clinical application of TMF for reconstruction of skull base defects after expanded endoscopic nasopharyngectomy. Methods Nine fresh cadaver heads (18 sides) were used for endoscopic dissection at the University of Pittsburgh School of Medicine in the United States. TMF was harvested using a traditional open approach and then transposed into the maxillary sinus and nasal cavity through the infratemporal fossa using an endoscopic transnasal transmaxillary approach. TMF length was then measured. Moreover, TMF was used for the reconstruction of skull base defects of six patients with recurrent nasopharyngeal carcinoma after expanded endoscopic nasopharyngectomy. Results The length of TMF harvested from the temporal line to the tip of the coronoid process of the mandible was 11.8 ± 0.9 cm. The widest part of the flap was 9.0 ± 0.4 cm. When TMF was dislocated from the coronoid process of the mandible, approximately another 2 cm of reach could be obtained. When the superficial layer of the temporalis muscle was split from the deep layer, the pedicle length could be extended 1.9 ± 0.2 cm. TMF could cover skull base defects in the anterior skull base, sellar, and clivus regions. Conclusion TMF can be used to reconstruct skull base defects after endoscopic expanded nasopharyngectomy and can effectively prevent the occurrence of serious complications in patients with recurrent nasopharyngeal carcinoma.

Large-Scale G Protein-Coupled Olfactory Receptor-Ligand Pairing.

G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diverse. This work investigated how the amino-acid sequences of olfactory receptors (ORs)-the largest GPCR family-encode diversified responses to various ligands. We established a proteochemometric (PCM) model based on OR sequence similarities and ligand physicochemical features to predict OR responses to odorants using supervised machine learning. The PCM model was constructed with the aid of site-directed mutagenesis, in vitro functional assays, and molecular simulations. We found that the ligand selectivity of the ORs is mostly encoded in the residues up to 8 Å around the orthosteric pocket. Subsequent predictions using Random Forest (RF) showed a hit rate of up to 58%, as assessed by in vitro functional assays of 111 ORs and 7 odorants of distinct scaffolds. Sixty-four new OR-odorant pairs were discovered, and 25 ORs were deorphanized here. The best model demonstrated a 56% deorphanization rate. The PCM-RF approach will accelerate OR-odorant mapping and OR deorphanization.