Microbubbles activated by low-frequency ultrasound enhance the anti-tumor effects of curcumin in glioma cells by suppressing the TGF-ß1/Smad/VEGF/NCAM signaling pathway.

This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-ß1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-ß. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-ß1/Smad/VEGF/NCAM signaling pathway by curcumin，and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.

Lipocalin-2 promotes neutrophilic inflammation in nasal polyps and its value as biomarker.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). METHODS: Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. RESULTS: LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. CONCLUSIONS: LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

The use of vestibular evoked myogenic potentials (VEMP) in the diagnosis of otolithic dysfunction of patients with obstructive sleep apnea: a survey of awareness and recognition of otorhinolaryngology medical staffs.

PURPOSE: To assess awareness and recognition of vestibular function tests in otorhinolaryngology medical staffs, especially the vestibular evoked myogenic potentials (VEMP) testing in patients with obstructive sleep apnea (OSA). METHODS: A survey was delivered via either email or a social media app. The medical staffs of the Chinese Medical Association of Otolaryngology Head and Neck Surgery from various branches were enrolled. Study data were collected and managed with an online data collection tool. RESULTS: A total of 1781 emails and 623 social media messages were sent to 2404 otorhinolaryngology medical staffs. One hundred and fifty-seven of them participated in the survey, including 24 via emails and 133 via the social media app. Regarding the knowledge of VEMP, only 59 (37.6%) of them agreed that OSA could be related to vertigo/dizziness/imbalance and 28 (17.8%) believed that OSA could result in VEMP abnormalities and would factor this in diagnosing the impairment of the vestibular function of OSA patients. A total of 7.6% of the respondents had never heard of the VEMP tests. Responses regarding the minimum age at which VEMP are possible ranged from younger than 6 months to greater than 18 years of age. Beliefs regarding the utility and reliability of VEMP varied, with 'unsure' being the most frequent response. In addition, only 17.8% of otolaryngologists indicated some access to the VEMP test. CONCLUSIONS: Knowledge and beliefs about the role of VEMP in diagnosing otolithic organ dysfunction caused by OSA in otorhinolaryngology vary widely. It is important for otorhinolaryngology medical staffs to learn the latest literatures and updated knowledge through continuing education.

Serum and glucocorticoid-regulated kinase 1 regulates transforming growth factor ß1-connective tissue growth factor pathway in chronic rhinosinusitis.

PURPOSE: Serum/glucocorticoid-regulated kinase 1 (SGK1) has been identified as a crucial regulator in fibrotic disorders. Herein, we explored SGK1 role in tissue remodeling of chronic rhinosinusitis (CRS). METHODS: Lentivirus was employed to generate an SGK1-overexpressing human bronchial epithelial cell (16HBE) line. To screen SGK1 downstream genes, RNA sequencing was performed on SGK1-overexpressing and control cell lines. To determine protein and gene expression levels, immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction were employed. Correlation analysis was performed using mRNA expression levels of SGK1, transforming growth factor ß1 (TGF-ß1), and connective tissue growth factor (CTGF) derived from CRS mucosal tissue and GEO database. Gene set enrichment analysis was conducted using gene sets from Molecular Signatures Database. The severity of symptoms in CRS patients was assessed using the 22-Item Sinonasal Outcome Test. RESULTS: SGK1 overexpression significantly increased the expression of connective tissue growth factor (CTGF) in 16HBE cells (P < 0.01). Consistently, CTGF protein level was considerably greater in mucosal tissue of CRS without nasal polyps (CRSsNP) than in CRS with nasal polyps (CRSwNP) (P < 0.05) or in control subjects (P < 0.01). TGF-ß1 protein level was higher in mucosal tissue of CRSsNP patients than in CRSwNP patients (P < 0.001) or in the control group (P < 0.01). mRNA levels of SGK1 and CTGF (P < 0.05, r = 0.668; P = 0.001, r = 0.630), TGF-ß1 and CTGF (P < 0.05, r = 0.560; P < 0.05, r = 0.420), as well as SGK1 and TGF-ß1(P < 0.05, r = 0.612; P < 0.05, r = 0.524) were significantly correlated in CRS mucosal tissue and GSE36830 dataset, respectively. TGF-ß1-induced upregulated genes were significantly enriched in SGK1 overexpression group. In vitro assays, TGF-ß1 promoted SGK1 and CTGF expression in a concentration- and time-dependent manner. Administrating an SGK1 inhibitor, GSK650394, significantly inhibited TGF-ß1-induced CTGF expression in 16HBE and dispersed primary nasal polyp cells. CONCLUSIONS: TGF-ß1 stimulation significantly increases SGK1 and CTGF expression. By regulating TGF-ß1-CTGF pathway, SGK1 may participate in tissue remodeling in the pathological mechanism of CRS.

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.

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.

The risk factors for residual juvenile nasopharyngeal angiofibroma and the usual residual sites.

OBJECTIVE: Juvenile nasopharyngeal angiofibroma (JNA) is non-metastasizing but potentially locally destructive tumor of the nasopharynx. It can destroy the skull base and invade into the cerebrum. Surgical management is the primary standard but residual disease is always a risk factor. We aimed to determine the risk factors for residual disease and usual sites for these residual tumors. METHODS: The medical records of 131 patients (mean age 17.6 ±â€¯6.8, range 9-71 years) with histologically proven JNA were retrospectively analyzed. The surgeries were all nasal endoscopic approaches, with or without assistant incision. RESULTS: The prevalence of residual disease was 16.8%. Risk factors associated with JNA recurrence included tumor stage, intraoperative bleeding, and the year in which the operation was performed. The pterygoid canal, pterygoid process, and pterygopalatine foramen were the most frequent locations for residual tumor. CONCLUSION: Surgical management should take particular care for the pterygoid canal, petrygoid process, and pterygopalatine foramen. Contrast-enhanced CT and MRI are effective tools to evaluate complete JNA excision in the first two days after primary surgery. Careful exploration of these areas may be the key to avoid residual JNA.

Cumulative sum analysis of the learning curve for endoscopic resection of juvenile nasopharyngeal angiofibroma.

BACKGROUND: To determine the learning curve with cumulative sum analysis for endoscopic resection of juvenile nasopharyngeal angiofibroma (JNA) and investigate whether the surgeon's expertise is a risk factor for recurrence. MATERIALS AND METHODS: We reviewed the medical records of patients with JNA who underwent endoscopic or endoscopic-assisted surgery between 2006 and 2015. We used cumulative sum (Cusum) analysis to plot the learning curve for operation time versus chronological sequence, and verified the Cusum curve by risk-adjusted Cusum (RA-Cusum) analysis. We identified three phases of expertise. The recurrence rate was analyzed using the Kaplan-Meier method and log-rank tests. A multivariable Cox regression analysis was performed to identify the independent risk factors for recurrence. RESULTS: We included 154 JNA patients with a median age of 16 years. The surgeon overcame the learning curve after case 80 with increasing surgical efficiency and competence. The learning curve plotted by Cusum analysis divided the cases into three phases: phase 1, accumulation of initial experience (cases 1-41); phase 2, further accumulation of experience (cases 42-117); and phase 3, mastering the procedure (cases 118-154). Pearson's χ2 tests showed that tumor stage (P = 0.021), blood loss (P = 0.001), operation time (P < 0.001), and phase (P < 0.001) were associated with recurrence. The log-rank test showed that time to recurrence was significantly shorter in phase 1 than in phases 2 and 3. Blood loss and phase were independently prognostic factors for time to recurrence, with P values of 0.023 and 0.009, respectively. The RA-Cusum analysis identified two inflection points of the curve at case 44 and 83, and verified the results of Cusum analysis. CONCLUSION: Surgical experience and competence with endoscopic resection affect the recurrence rate in JNA patients. LEVEL OF EVIDENCE: 4.

Endoscopic Repairs of Sinonasal Cerebrospinal Leaks: Outcome and Prognostic Factors.

OBJECTIVE: The aim of this study was to review the management of sinonasal cerebrospinal fluid (CSF) leaks and outcome of endoscopic repairs and to provide experience regarding leaks at the lateral wall of sphenoid sinus and the posterior wall of frontal sinus. METHODS: Patients who underwent endoscopic repairs of CSF leaks were reviewed. Characteristics of different etiologies were compared, and prognostic factors were analyzed. RESULTS: The study included 144 patients with 150 CSF leaks, in which spontaneous leaks account for 55%. Patients with traumatic leaks were significantly younger than those with spontaneous leaks (P = 0.012), and most traumatic leaks occurred in men (P < 0.001). The computed tomography scan showed an overall accuracy of 86.7%. For 17 leaks at the lateral wall of sphenoid sinus, transnasal (29%), transethmoid (24%), and transpterygoid (47%) approaches were used, with a success rate of 75%. For 11 defects at the posterior wall of the frontal sinus, 2 were managed by draf III surgery, and 3 by trephination-assisted procedure successfully. Success rate for primary repair was 95.6%, reaching 100% after a second repairing. Six leaks failed to be repaired included 4 spontaneous leaks, and 3 occurred at the lateral wall of the sphenoid sinus, 4 occurred in patients with elevated body mass index (BMI), 4 had evidence of raised intracranial pressure (ICP). CONCLUSION: Repair of leaks at lateral sphenoid sinus and posterior frontal sinus could achieve favorable results via selected endoscopic approaches. The failure of repair was associated with inaccessible leak sites, spontaneous leaks, raised ICP, and elevated BMI.

Recurrence of nonfamilial cardiac myxoma in the left ventricle: a case report.

A left atrial myxoma was found and removed in a 47-year-old woman admitted for acute ischemic cerebrovascular disease, without family history of cardiac tumor. Follow-up echocardiography, 15 months later, demonstrated a new myxoma in the left ventricle.

[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.

Single-cell transcriptome profiles the heterogeneity of tumor cells and microenvironments for different pathological endometrial cancer and identifies specific sensitive drugs.

Endometrial cancer (EC) is a highly heterogeneous malignancy characterized by varied pathology and prognoses, and the heterogeneity of its cancer cells and the tumor microenvironment (TME) remains poorly understood. We conducted single-cell RNA sequencing (scRNA-seq) on 18 EC samples, encompassing various pathological types to delineate their specific unique transcriptional landscapes. Cancer cells from diverse pathological sources displayed distinct hallmarks labeled as immune-modulating, proliferation-modulating, and metabolism-modulating cancer cells in uterine clear cell carcinomas (UCCC), well-differentiated endometrioid endometrial carcinomas (EEC-I), and uterine serous carcinomas (USC), respectively. Cancer cells from the UCCC exhibited the greatest heterogeneity. We also identified potential effective drugs and confirmed their effectiveness using patient-derived EC organoids for each pathological group. Regarding the TME, we observed that prognostically favorable CD8+ Tcyto and NK cells were prominent in normal endometrium, whereas CD4+ Treg, CD4+ Tex, and CD8+ Tex cells dominated the tumors. CXCL3+ macrophages associated with M2 signature and angiogenesis were exclusively found in tumors. Prognostically relevant epithelium-specific cancer-associated fibroblasts (eCAFs) and SOD2+ inflammatory CAFs (iCAFs) predominated in EEC-I and UCCC groups, respectively. We also validated the oncogenic effects of SOD2+ iCAFs in vitro. Our comprehensive study has yielded deeper insights into the pathogenesis of EC, potentially facilitating personalized treatments for its varied pathological types.

Immune landscape and heterogeneity of cervical squamous cell carcinoma and adenocarcinoma.

Despite the differences in disease outcomes and pathological features between cervical squamous cell carcinoma (CSCC) and adenocarcinoma (ADC), the molecular characteristics in immune heterogeneity of the tumor microenvironment remain unclear. Here, we explored the immune landscape and heterogeneity between CSCC and ADC. Gene expression and clinical characteristics of cervical carcinoma from The Cancer Genome Atlas (TCGA) were downloaded. Differentially expressed genes (DEGs), immune cell infiltration, and pathway enrichment analyses were used to explore the immune landscape and heterogeneity between CSCC and ADC. Furthermore, distinct immune signatures between CSCC and ADC were validated based on clinical samples. In total, 4,132 upregulated DEGs and 2,307 down-regulated DEGs were identified between CSCC and ADC, with enrichments in immune related-pathways in CSCC. In addition, 54 hub DEGs correlated with patients' prognosis and immunocytes infiltration were identified. The CSCC patients had a higher ImmuneScore and more abundant immunocytes infiltration compared to ADC patients, as validated by immunohistochemistry (IHC) and multicolor immunofluorescence (mIF) analyses of collected samples. Furthermore, CSCC displayed higher inhibitory immune checkpoints expression, tumor mutation burden (TMB), and microsatellite instability (MSI) compared to ADC, which indicated CSCC patients were more likely to benefit from immunotherapy. In summary, our results revealed the huge immune heterogeneity between CSCC and ADC, and provided guidance for immunotherapy selection for different pathological types of cervical cancer.

Survival Analysis and Prognostic Factors After Endonasal Resection of Advanced Olfactory Neuroblastomas: A Single Institution Experience.

OBJECTIVES: To explore the prognostic factors in patients with advanced olfactory neuroblastoma (ONB) underwent endoscopic surgery. MATERIALS AND METHODS: Retrospective medical records were reviewed of patients with pathologically proven ONB who underwent endoscopic surgical resection. Clinicopathological characteristics including patient demographics, treatment, complications, follow-up, and outcomes were analyzed. Kaplan-Meier overall survival (OS) and disease-free survival (DFS) curves were plotted. Univariate and multivariate Cox regression models were used to determine prognostic factors. RESULTS: Eighty-five patients with Kadish stage C ONB were examined. According to the various staging systems used, most patients harbored modified Kadish stage C (78.8%). Twenty-six patients (30.6%) underwent bony skull base resection, 11 (12.9%) underwent dura resection, and 24 (28.2%) underwent additional intracranial resection that included the olfactory bulb and duct. Median follow-up was 39 months. Five-year OS and DFS rates were 83.7% and 74.9%, respectively. Five-year OS was 100% in patients treated with bony skull base resection and 77.5% in those who were not (P = .052). Dura resection did not improve OS. Multivariate Cox regression analysis identified perioperative complications (P = .009), gross total resection (P = .004), orbital invasion (P = .014), postoperative radiotherapy (P = .030), and bony skull base resection (P = .019) as independent prognostic predictors. CONCLUSION: For patients with advanced ONB, endoscopic surgery in conjunction with radiotherapy and chemotherapy is effective and safe. Dura resection should be performed with caution in selected patients to balance survival and complications. Postoperative radiotherapy is important to improve OS and DFS.

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.

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.

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.

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.

Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the world's most common head and neck cancer. However, the immune infiltration phenotypes of LSCC have not been well investigated. Methods: The multi-omics data of LSCC were obtained from the TCGA (n=111) and GEO (n=57) datasets. The infiltrations of the 24 immune cell populations were calculated using the GSVA method. Then LSCC samples with different immune cell infiltrating patterns were clustered, and the multi-omics differences were investigated. Results: Patients were clustered into the high-infiltration and low-infiltration groups. The infiltration scores of most immune cells were higher in the high-infiltration group. Patients with high-infiltration phenotype have high N and TNM stages but better survival, as well as less mutated COL11A1 and MUC17. Common targets of immunotherapies such as PD1, PDL1, LAG3, and CTLA4 were significantly up-regulated in the high-infiltration group. The differentially expressed genes were mainly enriched in several immune-related GOs and KEGG pathways. Based on the genes, miRNAs, and lncRNAs differentially expressed in both the TCGA and GEO cohorts, we built a ceRNA network, in which BTN3A1, CCR1, miR-149-5p, and so on, located at the center. A predictive model was also constructed to calculate a patient's immune infiltration phenotype using 16 genes' expression values, showing excellent accuracy and specificity in the TCGA and GEO cohorts. Conclusions: In this study, the immune infiltration phenotypes of LSCC and the corresponding multi-omics differences were explored. Our model might be valuable to predicting immunotherapy's outcome.

Identification of Heat Shock Protein 90 as a Recurrence Related Marker in Juvenile Nasopharyngeal Angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a highly recurrent tumor after curative surgery. OBJECTIVE: The purpose of this study was to evaluate heat shock protein 90 (HSP90) expression in JNA and its association with tumor recurrence. METHODS: Immunohistochemistry was performed to assess HSP90 expression using tissue microarrays containing 70 JNA patients and 10 control subjects. The associations of HSP90 expression with clinicopathological features and tumor recurrence were analyzed. RESULTS: Immunohistochemistry revealed high HSP90 expression in JNA compared with normal middle turbinate samples. High expression of HSP90, which correlated with MVD (P = .001), ER-α (P = .001), VEGF (P < .001) and JNA recurrence (P = .009), was an independent prognostic factor of time to recurrence (P = .017). The combination of HSP90 and ER-α had a better power to predict disease recurrence than other clinicopathological features (P = .008). CONCLUSIONS: HSP90 may be an independent prognostic marker in JNA patients administered surgical treatment. Combination of HSP90 and ER-α expression may be the best predictor of tumor recurrence among all clinicopathological factors.