Preliminary evidence for endoscopic surgery combined with postoperative anti-PD-1 immunotherapy in advanced recurrent nasopharyngeal carcinoma.

BACKGROUD: Endoscopic surgery can be used as the main treatment for advanced recurrent nasopharyngeal carcinoma (rNPC). However, there is a huge clinical controversy about the need for consolidated immunotherapy after surgery. METHODS: We performed a retrospective propensity score-matched analysis (1:2) of patients with locally advanced rNPC who underwent endoscopic nasopharyngectomy (ENPG) combined with anti-programmed cell death protein-1 (PD-1) monotherapy or ENPG alone. The survival rate was analyzed by Kaplan-Meier method. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Potential surgical-related complications and immune-related adverse events (AEs) were also assessed. RESULTS: We recruited 10 patients receiving ENPG plus anti-PD-1 monotherapy and 20 receiving ENPG alone. During the mean follow-up of 23.8 months, a significant improvement in the 2-year PFS was detected in the consolidation immunotherapy group compared to the ENPG alone group (80.0% vs. 40.0%; HR = 0.258; 95% CI: 0.09-0.72; p = 0.04), while the 2-year OS in the consolidation immunotherapy group was not significantly longer than that in the ENPG alone group (90.0% vs. 75.0%; HR = 0.482; 95% CI: 0.08-3.00; p = 0.50). The incidence of surgical-related complications in the consolidation immunotherapy group and ENPG alone group was 70.0 and 60.0%, respectively. Immune-related AEs were similar between the toripalimab arm (75.0%) and the camrelizumab arm (66.7%). Surgical-related complications depend on symptomatic treatments. Immune-related AEs were mild and tolerable. CONCLUSIONS: Consolidation immunotherapy regimen for patients with advanced rNPC after ENPG compared to ENPG alone provides a superior PFS rate with a manageable safety profile.

Subjective symptoms as predictors for eosinophilic chronic rhinosinusitis with nasal polyps in the Chinese population.

PURPOSE: To evaluate the putative association between subjective symptoms and eosinophilic inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A total of 102 patients with CRSwNP who underwent endoscopic sinus surgery were prospectively enrolled. The Sinonasal Outcomes Test-22 scores (SNOT-22), EuroQol 5-dimensional Questionnaire scores (ED-5D), and Lund-Mackay scores by computed tomography (CT) were obtained. Patients were grouped as eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). ECRSwNP was defined if tissue eosinophils of nasal polyps were greater than or equal to 8/HPF according to positive major basic protein (MBP) staining, and neCRSwNP otherwise. RESULTS: Thirty neCRSwNP and 72 eCRSwNP patients were included. ECRSwNP patients had higher incidences of asthma (p = 0.001), allergic rhinitis (p = 0.001), and ethmoid-to-maxillary opacification ratio on CT scans (p < 0.001), whereas the proportion of purulent discharge (p < 0.001) and maxillary sinus score (p = 0.002) was higher in the neCRSwNP patients. There were no significant differences between patients on the mains of the EQ-5D health utility values and total SNOT-22 score. However, eCRSwNP patients had higher SNOT-22 scores of sneezing (p = 0.006), runny nose (p < 0.001), and ear/facial domain (p = 0.012), and lower scores of thick nasal discharge (p = 0.015) and blockage (p = 0.042). Sneezing, thick nasal discharge, and blockage/congestion of nose were recognized as independent factors of CRSwNP. CONCLUSION: Sneezing was an independent predictor of eCRSwNP, and thick nasal discharge and blockage/congestion of nose were independent predictors of neCRSwNP.

Analysis of molecular ligand functionalization process in nano-molecular electronic devices containing densely packed nano-particle functionalization shells.

Molecular electronic devices based on few and single-molecules have the advantage that the electronic signature of the device is directly dependent on the electronic structure of the molecules as well as of the electrode-molecule junction. In this work, we use a two-step approach to synthesise functionalized nanomolecular electronic devices (nanoMoED). In first step we apply an organic solvent-based gold nanoparticle (AuNP) synthesis method to form either a 1-dodecanethiol or a mixed 1-dodecanethiol/ω-tetraphenyl ether substituted 1-dodecanethiol ligand shell. The functionalization of these AuNPs is tuned in a second step by a ligand functionalization process where biphenyldithiol (BPDT) molecules are introduced as bridging ligands into the shell of the AuNPs. From subsequent structural analysis and electrical measurements, we could observe a successful molecular functionalization in nanoMoED devices as well as we could deduce that differences in electrical properties between two different device types are related to the differences in the molecular functionalization process for the two different AuNPs synthesized in first step. The same devices yielded successful NO2gas sensing. This opens the pathway for a simplified synthesis/fabrication of molecular electronic devices with application potential.

The Antiproliferative and Antifibrotic Effects of Cisplatin on Primary Human Vocal Fold Fibroblasts.

OBJECTIVE: Vocal fold scarring and laryngeal stenosis are major clinical challenges. Current drugs do not efficiently reduce scarring. We examined the antiproliferative and antifibrotic effects of cisplatin on primary human vocal fold fibroblasts (HVFFs). METHODS: HVFFs were cultured in vitro and identified by immunocytochemistry. The relative viability of HVFFs was analyzed by Cell Counting Kit-8 assays (CCK-8). The fibrogenic phenotype was induced by transforming growth factor-ß1 (TGF-ß1) and reversed by cisplatin as shown by immunocytochemistry. Real-time PCR and Western blotting assessed collagen III and I. Western blotting for Smad2, p-Smad2, Smad-3, p-Smad3 and caspase-3 were performed. RESULTS: CCK-8 results showed that cisplatin decreased the relative viability of HVFFs, and Western blots revealed elevation of the apoptosis-related protein caspase-3 in HVFFs. Cisplatin treatment reduced α-smooth muscle actin staining intensity in the presence of TGF-ß1. Real-time PCR revealed the downregulation of collagen III and I in cisplatin-treated HVFFs. The TGF-ß1-induced increased fibrogenic protein levels were decreased by cisplatin. Reduced levels were detected at late time points. CONCLUSIONS: Cisplatin induces antiproliferative and antifibrotic alterations in HVFFs. Cisplatin may prevent postoperative vocal fold scarring and laryngeal stenosis in patients treated with CO2 laser microsurgery and undergoing delayed wound healing.

The promising role of miRNAs in radioresistance and chemoresistance of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor that develops in the nasopharynx. It has a distinct ethnic and geographical distribution, and emerging evidence suggests that it is an ecological disease. Most patients respond well to radiation combined with chemotherapy as the primary treatment for NPC. However, some patients will eventually develop radio resistance and chemoresistance, resulting in recurrence and metastasis, which is a primary cause of poor prognosis. The processes underlying radio resistance and chemoresistance in NPC are complex and unknown. MicroRNAs (miRNAs) are endogenic non-coding RNA molecules. They play a role in a variety of cell functions as well as development of disease such as cancer. There has been considerable data demonstrating the existence of numerous aberrant miRNAs in cancer tissues, cells, and biofluids, which indicates the importance of studying the influence of miRNAs on NPC. Therefore, this review comprehensively analyzes the elaborate mechanisms of miRNAs affecting the radio resistance and chemoresistance of NPC. Multiple tumor-specific miRNAs can be employed as therapeutic and prognostic biological indicators.

Nasal Presentations of Rosai-Dorfman Disease: Clinical Manifestation and Treatment Outcomes.

PURPOSE: There has been a lack of evidence-based management strategies on the nasal presentations of Rosai-Dorfman disease (RDD). We aim to investigate the clinical manifestation, treatment, and outcomes in patients with nasal RDD. METHODS: We retrospectively reviewed available medical records of patients diagnosed with nasal RDD from 2014 to 2021 at our department. RESULTS: A total of 26 patients were included with a marked female preponderance (2.25:1). The most common symptom and affected sites were nasal congestion (31%) and nasal cavity (73%), respectively. The average times of biopsies was 1.5 times (range: 1-3). The histiocytes were positive about S100 and CD68 and negative for CD1a with common emperipolesis. The mean duration of follow-up was 34 months (range, 3-87). One patient with concomitant nasal small B-cell lymphoma achieved complete remission after chemoradiotherapy. Recommended treatments were endoscopic resection (92%) and oral corticosteroids (21%). Surgery was performed to remove the resectable lesion as completely as possible. Corticosteroids induced almost 100% overall remission. Of the relapses, two patients achieved an overall response and one remained in progressive stage after subsequent excision. Two patients only received dissection biopsy that responded to oral corticosteroid administration and combined therapies of lenalidomide and dexamethasone, respectively. CONCLUSIONS: Diffuse lesions in nasal cavity and sinuses, and even widely affected nasal skull base, laryngopharynx, orbit, and cavernous sinus, should be considered the possibility of Rosai-Dorfman disease. Characteristic immunohistochemical staining is helpful for the diagnosis. Endoscopic surgical therapy remains the mainstream treatment for patients enduring an unbearable course. Oral corticosteroid administration serves as an adjuvant therapy for first-line treatments.

The Impact of Endoscopic Endonasal Surgery on Quality of Life in Patients with Malignant Tumors of the Anterior Skull Base: A Prospective Study.

Objective: To investigate the effects of endoscopic endonasal surgery (EES) on longitudinal quality of life (QoL) in patients with malignant tumors of the anterior skull base. Methods: Eligible patients prospectively completed the Anterior Skull Base Surgery Questionnaire (ASBQ) and the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires in referring to 3 different periods throughout their treatment and recovery. Results: Forty patients were included. The median volume coronal maximum length of the tumor was 3.6 cm (95% CI 2.7-4.1cm). Overall QoL significantly worsened at 1 month postoperatively but returned to baseline after 1 year. Unrelieved symptoms in specific domains prompted further evaluation of individual items. Transient worsening of taste (p=0.011) and olfaction (p=0.004) lasted for 1 month but gradually relieved within the first postoperative year, but vision consistently worsened over the course of the treatment (p=0.126). Age>50 years (p<0.001), comorbidities (p<0.001), tumor necrosis (p<0.001) and recurrence (p=0.001) were associated with worse preoperative QoL. Poor long-term QoL was noted in those undergoing adjuvant therapy (p=0.032). Overall ASBQ scores (p=0.024), subdomain scores in specific symptoms (p=0.016), and vision scores (p=0.009) were worse only in patients with the greater coronal maximum diameter at 1-month postoperatively. Greater coronal maximum diameter was related to worse preoperative subdomain scores regarding specific symptoms (p=0.030) and decreased postoperative long-term decreased vision scores (p=0.014). Conclusion: Long-term site-specific and sinonasal QoL eventually stabilized after EES. Greater coronal maximum diameter was significantly associated with worsened vision function. Temporarily worse olfactory, vision, and taste function may be tied to decreased short-term QoL.

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.

Expression and Prognostic Value of Lgr5 in Patients with Recurrent Nasopharyngeal Carcinoma.

Background: As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous. Materials: We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis. Results: Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively). Conclusion: Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients.

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.

Endoscopic Endonasal Surgery for Dermoid Cysts Arising From the Middle Cranial Fossa Floor: A Rare Case Series.

OBJECTIVE: Dermoid cysts (DCs) are congenital, slowly growing, and may cause nervous system symptoms. Related literature is limited and mainly includes case reports. We report a case series of DCs originating from the middle cranial fossa floor (MCFF) and investigate their demographic information, clinical characteristics, imaging findings, surgical procedures, and prognostic outcomes. METHODS: We reviewed the patients with DCs arising from the MCFF undergoing endoscopic endonasal surgery (EES) in our center between 2012 and 2022. RESULTS: A total of 5 patients with DCs were enrolled (2 males and 3 females), with a mean age of 46.2 years at the onset. All DCs originated from the MCFF with 1 case involving the middle cranial fossa bone and another 1 case affecting the dura mater. One (20.0%) patient had neurological involvement. After admission, all patients received EES with a total resection rate of 100.0% (5 of 5). After a median follow-up of 73.2 months, all patients achieved complete clinical and radiological improvements. No surgical-related complications or relapses were observed during the long-term follow-up. CONCLUSION: Endoscopic endonasal surgery is considered a safe and effective approach for the treatment of DCs in the MCFF. A larger sample size and longer follow-up time are needed.

Aerial-aquatic robots capable of crossing the air-water boundary and hitchhiking on surfaces.

Many real-world applications for robots-such as long-term aerial and underwater observation, cross-medium operations, and marine life surveys-require robots with the ability to move between the air-water boundary. Here, we describe an aerial-aquatic hitchhiking robot that is self-contained for flying, swimming, and attaching to surfaces in both air and water and that can seamlessly move between the two. We describe this robot's redundant, hydrostatically enhanced hitchhiking device, inspired by the morphology of a remora (Echeneis naucrates) disc, which works in both air and water. As with the biological remora disc, this device has separate lamellar compartments for redundant sealing, which enables the robot to achieve adhesion and hitchhike with only partial disc attachment. The self-contained, rotor-based aerial-aquatic robot, which has passively morphing propellers that unfold in the air and fold underwater, can cross the air-water boundary in 0.35 second. The robot can perform rapid attachment and detachment on challenging surfaces both in air and under water, including curved, rough, incomplete, and biofouling surfaces, and achieve long-duration adhesion with minimal oscillation. We also show that the robot can attach to and hitchhike on moving surfaces. In field tests, we show that the robot can record video in both media and move objects across the air/water boundary in a mountain stream and the ocean. We envision that this study can pave the way for future robots with autonomous biological detection, monitoring, and tracking capabilities in a wide variety of aerial-aquatic environments.

The Role of Cytokines in Modulating Vocal Fold Fibrosis: A Contemporary Review.

OBJECTIVES: Vocal fold (VF) scarring and laryngeal stenosis are a significant clinical challenge. Excessive scar formation causes low voice quality or even life-threatening obstructions. Cytokines are thought to modulate multiple steps of the establishment of VF fibrosis, but there is no systematic report regarding their role in modulating VF fibrosis. This review aims to investigate the role of cytokines in modulating vocal fold fibrosis. STUDY DESIGN: Literature review. METHODS: This review searched for all relevant peer publications in English for the period 2009 to 2019 in the PubMed database using search terms: "laryngeal stenosis," "vocal fold scarring," and "cytokines." A thorough investigation of the methods and results of the reviewed studies was performed. RESULTS: Comprehensive research in various studies, including analyses of prostaglandin E2 (PGE2), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), transforming growth factor-ß3 (TGF-ß3), and interleukin-10 (IL-10), supports cytokine therapy for VF scarring and laryngeal stenosis to some extent. A few clinical studies on this topic support the conclusion that HGF and bFGF can be selected as effective drugs, and no serious side effects were found. CONCLUSIONS: This review describes the potential of cytokines for modulating the process of VF fibrogenesis, although cytokines are still an unproven treatment method. As no ideal drugs exist, cytokines may be considered the candidate treatment for preventing VF fibrogenesis. Laryngoscope, 131:139-145, 2021.

Highly Efficient SO2 Sensing by Light-Assisted Ag/PANI/SnO2 at Room Temperature and the Sensing Mechanism.

Sulfur dioxide (SO2) is one of the most hazardous and common environmental pollutants. However, the development of room-temperature SO2 sensors is seriously lagging behind that of other toxic gas sensors due to their poor recovery properties. In this study, a light-assisted SO2 gas sensor based on polyaniline (PANI) and Ag nanoparticle-comodified tin dioxide nanostructures (Ag/PANI/SnO2) was developed and exhibited remarkable SO2 sensitivity and excellent recovery properties. The response of the Ag/PANI/SnO2 sensor (20.1) to 50 ppm SO2 under 365 nm ultraviolet (UV) light illumination at 20 °C was almost 10 times higher than that of the pure SnO2 sensor. Significantly, the UV-assisted Ag/PANI/SnO2 sensor had a rapid response time (110 s) and recovery time (100 s) to 50 ppm SO2, but in the absence of light, the sensors exhibited poor recovery performance or were even severely and irreversibly deactivated by SO2. The UV-assisted Ag/PANI/SnO2 sensor also exhibited excellent selectivity, superior reproducibility, and satisfactory long-term stability at room temperature. The increased charge carrier density, improved charge-transfer capability, and the higher active surface of the Ag/PANI/SnO2 sensor were revealed by electrochemical measurements and endowed with high SO2 sensitivity. Moreover, the light-induced formation of hot electrons in a high-energy state in Ag/PANI/SnO2 significantly facilitated the recovery of SO2 by the gas sensor.

[A non-resonance surface-enhanced Raman spectroscopic study of hemin on a roughened silver electrode].

The non-resonance Raman spectra of hemin were studied with the excitation of a 632.8 nm laser. The results indicated that the spectra of oxidized and reduced hemin are dominated by B1g vibration modes. The SERS spectral feature demonstrates that the porphyrin plane is perpendicular to the electrode surface. Moreover, the enhancement of the bands related to propionic acid substituents indicates that hemin is attached to the electrode surface via propionic acid substituents. The dependence of the SERS spectra on the electrode potential was examined. One of the B1g modes, nu 15, was found to be highly sensitive to the oxidation state of the central iron in heme group, and thereby exclusively assigned to be the oxidation state marker band for heme iron.