[Clinical classification, staging and treatment strategy of radionecrosis of the nasopharynx and skull base].

Objective:To establish a staging system for guiding clinical treatment and prognostic risk assessment by retrospectively analyzing the cases with radionecrosis of the nasopharynx and skull base （RNSB） after radiotherapy for nasopharyngeal carcinoma. Methods:A total of 86 cases of RNSB from January 2019 to December 2022 visited Department of Otorhinolaryngology Head and Neck, the People's Hospital of Guangxi Zhuang Autonomous Region. Seventeen patients gave up the treatment, and 69 patients who underwent treatment were included for analysis. By analyzing the results of electronic nasopharyngolaryngoscopy combined with magnetic resonance （MR）, CT, and other imaging examinations, a staging system for RNSB was proposed. The relationship between the staging system and the surgical effectiveness and clinical prognosis was further analyzed. Results:According to the severity and extent of destruction of soft tissue, bone, and the adjacent neurovascular structures, the RNSB was categorized into closed type （n=5） and open type （n=64）, of which the open type was subdivided into five types: type Ⅰ（n=4）, type Ⅱ（n=6）, type Ⅲ（n=39, of which 21 cases were type Ⅲa and 18 cases were type Ⅲb）, type Ⅳ（n=12）, and type Ⅴ（n=8）. The clinical stage of RNSB were classified based on nasopharyngolaryngoscopy and imaging examinations, receiving the second course of radiotherapy or not, the involvement of the infection site, the extent of bone destruction, the degree of internal carotid artery involvement, and the degree of brain tissue necrosis: stageⅠ（1-2 scores）, 11 cases at stageⅡ（3-4 scores）, 24 cases at stage Ⅲ（5-6 scores）, and 30 cases at stage Ⅳ（ ≥ 7 scores or more）. Twenty-two patients chose conservative treatment （2 patients at stage Ⅰ, 3 patients at stage Ⅱ, 7 patients at stage Ⅲ, and 10 patients at stage Ⅳ）. Forty-seven patients chose nasal endoscopic surgical treatment （2 patients at stage Ⅰ, 8 patients at stage Ⅱ, 17 patients at stage Ⅲ, and 20 patients at stage Ⅳ）, of which 16 cases had received free mucosal flap and/or stented septum mucosal flap repair. Patients at stages Ⅰ, Ⅱ, and Ⅲ achieved satisfactory efficacy after surgical treatment. In addition, higher clinical stage was found to correlate with the worse prognosis and higher incidence of perioperative complications, which included failure of healing because of surgical site infection, cerebrospinal fluid nasal leakage, progressive osteonecrosis, nasopharyngeal hemorrhage, and death. Conclusion:The staging system proposed in our study can be used for early detection of RNSB during regular follow-up, and is also valuable for clinical treatment guidance and prognosis assessment.

[Effect of endoscopic surgery combined with chemotherapy and radiotherapy on prognosis of early nasopharyngeal carcinoma patients in high incidence area].

Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinoma（T1-2N0M0） who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy group（n=34, treated with endoscopic surgery combined with chemotherapy） and the surgery + radiotherapy group（n=34, treated with endoscopic surgery combined with radiotherapy）. Propensity score matching was used to match the patient data between the two groups at a 1∶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groups（all P>0.05）. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groups（both P>0.05）. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group （all P> 0.05） Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.

[Radiation-induced sarcoma in patients with nasopharyngeal carcinoma: a single-institution retrospective study].

Objective:To analyze the clinical features, treatment methods and prognosis of radiation-induced sarcoma（RIS） of the head and neck after radiotherapy for nasopharyngeal carcinoma（NPC）, and explore its treatment strategies. Methods:A retrospective analysis was conducted on RIS patients after radiotherapy for NPC in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2013 to October 2022. The time of onset, lesion location, pathological subtypes, imaging features and treatment outcomes were described, and the median survival time was statistically analyzed through follow-up. Results:This study included 10 patients with an interval of 2-27 years between NPC and RIS. The nasopharynx was the more common site of RIS, and osteosarcoma was the main pathological type. The median overall survival was 18 months. The median survival was 40 months in the surgery combined with the chemotherapy group, and 12 months in the surgery alone group. The 1-and 2-year cumulative survival rates were 48% and 36%, respectively. Prognostic analysis showed that gender, age of onset, time of sarcoma onset after radiotherapy and treatment methods might not be influencing factors for prognosis, and osteosarcomas presented a poorer prognosis than other pathological types. Conclusion:RIS is one of the most severe long-term adverse effects in patients with NPC. The prognosis of RIS is poor, and complete surgical resection of the tumor can improve patient survival rates. In cases where complete surgical resection is challenging, radiotherapy or chemotherapy may offer some improvement in tumor control.

[Diagnosis of nasopharyngeal carcinoma with convolutional neural network on narrowband imaging].

Objective:To evaluate the diagnostic accuracy of the convolutional neural network（CNN） in diagnosing nasopharyngeal carcinoma using endoscopic narrowband imaging. Methods:A total of 834 cases with nasopharyngeal lesions were collected from the People's Hospital of Guangxi Zhuang Autonomous Region between 2014 and 2016. We trained the DenseNet201 model to classify the endoscopic images, evaluated its performance using the test dataset, and compared the results with those of two independent endoscopic experts. Results:The area under the ROC curve of the CNN in diagnosing nasopharyngeal carcinoma was 0.98. The sensitivity and specificity of the CNN were 91.90% and 94.69%, respectively. The sensitivity of the two expert-based assessment was 92.08% and 91.06%, respectively, and the specificity was 95.58% and 92.79%, respectively. There was no significant difference between the diagnostic accuracy of CNN and the expert-based assessment （P=0.282, P=0.085）. Moreover, there was no significant difference in the accuracy in discriminating early-stage and late-stage nasopharyngeal carcinoma（P=0.382）. The CNN model could rapidly distinguish nasopharyngeal carcinoma from benign lesions, with an image recognition time of 0.1 s/piece. Conclusion:The CNN model can quickly distinguish nasopharyngeal carcinoma from benign nasopharyngeal lesions, which can aid endoscopists in diagnosing nasopharyngeal lesions and reduce the rate of nasopharyngeal biopsy.

Efficacy of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of nasopharyngeal carcinoma with cervical lymph node metastasis.

OBJECTIVES: First, we retrospectively compared the clinical efficacy of concurrent chemoradiotherapy combined with nimotuzumab vs. chemoradiotherapy alone in patients with nasopharyngeal carcinoma (NPC) and cervical lymph node metastasis. Second, we analyzed the value of Ki-67 as a predictor of nimotuzumab efficacy. METHODS: From January 2012 to December 2019, 1250 patients with cervical lymph node metastasis eligible for enrollment were included, of whom 383 were treated with concurrent chemoradiotherapy combined with nimotuzumab (targeted therapy group), and 867 were treated with concurrent chemoradiotherapy (CRT group). A total of 381 pairs of patients were matched using 1:1 propensity score matching, and differences in clinical prognosis were compared between the two groups. RESULTS: Overall survival (OS) (P = 0.028), disease-free survival (DFS) (P = 0.040), and distant metastasis-free survival (DMFS) (P = 0.040) were better in the targeted therapy compared to the CRT group. Multivariate analysis revealed that clinical staging, chemotherapy, and nimotuzumab therapy were predictors of OS and DFS. In the targeted therapy group, patients with ≥ 50% Ki-67 positivity had better OS and DFS rates than those with < 50% Ki-67 positivity. CONCLUSIONS: In patients with stage N1-3 NPC and lymph node metastasis, the addition of nimotuzumab to concurrent chemoradiotherapy may provide additional survival benefits. Ki-67 is a potential biomarker with clinical predictive value for the efficacy of nimotuzumab combined with chemoradiotherapy.

Fluid dynamics of the upper airway in pediatric patients with severe laryngomalacia.

Laryngomalacia is the top cause of pediatric laryngeal wheeze. We used computational fluid dynamics to study the inspiratory airflow dynamics in severe pediatric laryngomalacia. Computed tomography was performed on the upper airways of two infants, one with severe laryngomalacia and one with normal airway, and 3D models were reconstructed. ANSYS CFD-POST software was used to simulate airflow in these models to compare the volumetric flow rate, flow velocity, pressure, wall shear, and vortex. The volume flow rate in the laryngomalacia model was significantly reduced compared with the control model. Under inspiratory pressures, the peak flow velocity, pressure, and shear force in the control model appeared at the soft palate stenosis, while that in the laryngomalacia model appeared at the supraglottis stenosis. In both models, the maximum flow velocity and shear force increased with decreasing inspiratory pressure, while the minimum pressure decreased with decreasing inspiratory pressure. In the control model, the airflow vortex appeared anteriorly below the posterior section of the soft palate. In the laryngomalacia model, the vortex appeared anteriorly below the posterior section of the soft palate and anteriorly below the vocal folds. Our methodology provides a new mechanistic understanding of pediatric laryngomalacia.

Epithelial-mesenchymal transition classification of circulating tumor cells predicts clinical outcomes in progressive nasopharyngeal carcinoma.

Background: Liquid biopsy facilitates the enrichment and isolation of circulating tumor cells (CTCs) in various human cancers, including nasopharyngeal carcinoma (NPC). Characterizing CTCs allows observation of the evolutionary process of single tumor cells undergoing blood-borne dissemination, such as epithelial-mesenchymal transition. However, the prognostic value of phenotypic classification of CTCs in predicting the clinical outcomes of NPC remains poorly understood. Patients and methods: A total of 92 patients who met the inclusion criteria were enrolled in the present study. The CanPatrol™ CTC technology platform was employed to isolate CTCs, and an RNA in situ hybridization-based system was used for phenotypic classification. Kaplan-Meier survival curves were used for univariate survival analysis, and the log-rank test was performed for between-group comparisons of the survival curves. Results: CTCs were detected in 88.0% (81/92) of the enrolled patients with NPC. The total CTC number did not vary between the T and N stages or between Epstein-Barr virus DNA-positive and -negative cases. The numbers of total CTCs and epithelial/mesenchymal (E/M) hybrid CTCs decreased significantly at 3 months post concurrent chemoradiotherapy (P=0.008 and P=0.023, respectively), whereas the numbers of epithelial or mesenchymal CTCs did not decrease. E/M hybrid-predominant cases had lower disease-free survival (P=0.043) and distant metastasis-free survival (P=0.046) rates than non-E/M hybrid-predominant cases. Conclusion: CTC classification enables a better understanding of the cellular phenotypic alterations responsible for locoregional invasion and distant metastasis in NPC. E/M hybrid-predominant CTC distribution predicts unfavorable clinical outcomes in patients with progressive NPC.

Prognostic value of hypothyroidism in patients undergoing intensity-modulated radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. METHODS: The clinical data of 284 NPC patients, who received intensity-modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. RESULTS: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease-free survival (DFS) (p = 0.002) and relapse-free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). CONCLUSIONS: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required.

Long intergenic non-protein coding RNA 02570 promotes nasopharyngeal carcinoma progression by adsorbing microRNA miR-4649-3p thereby upregulating both sterol regulatory element binding protein 1, and fatty acid synthase.

Our previous studies have elucidated a possible connection between long intergenic non-protein coding RNA 2570 (LINC02570) and nasopharyngeal carcinoma (NPC). However, the precise mechanism by which LINC02570 promotes NPC remains unknown. We used quantitative polymerase chain reaction (qPCR) to detect LINC02570 expression in nasopharyngeal cell lines, NPC tissues, and chronic rhinitis tissues. Subcellular LINC02570 localization was confirmed by fluorescence in situ hybridization (FISH). The effects of LINC02570 stable knockdown and overexpression on viabillity, proliferation, migration, and invasion were analyzed using 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl-2-H-Tetrazolium bromide (MTT), a colorimetric focus-formation assay, a wound healing assay, and transwell assays. RNA crosstalk analysis in silico predicted microRNA-4649-3p (miR-4649-3p) binding to LINC02570 or sterol regulatory element binding transcription factor 1 (SREBF1). A dual luciferase reporter assay was used to confirm potential interactions. Sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression were detected by western blotting. The results suggest that LINC02570 is upregulated in late clinical stage NPC patients, and promotes NPC progression by adsorbing miR-4649-3p to up-regulate SREBP1 and FASN. This study elucidates a potential chemotherapeutic target involved in lipid metabolism in NPC.

Store-operated Ca2+ entry as a key oncogenic Ca2+ signaling driving tumor invasion-metastasis cascade and its translational potential.

Tumor metastasis is the primary cause of treatment failure and cancer-related deaths. Store-operated Ca2+ entry (SOCE), which is mediated by stromal interaction molecules (STIM) and ORAI proteins, has been implicated in the tumor invasion-metastasis cascade. Epithelial-mesenchymal transition (EMT) is a cellular program that enables tumor cells to acquire the capacities needed for migration and invasion and the formation of distal metastases. Tumor-associated angiogenesis contributes to metastasis because aberrantly developed vessels offer a path for tumor cell dissemination as well as supply sufficient nutrients for the metastatic colony to develop into metastasis. Recently, increasing evidence has indicated that SOCE alterations actively participate in the multi-step process of tumor metastasis. In addition, the dysregulated expression of STIM/ORAI has been reported to be a predictor of poor prognosis. Herein, we review the latest advances about the critical role of SOCE in the tumor metastasis cascade and the underlying regulatory mechanisms. We emphasize the contributions of SOCE to the EMT program, tumor cell migration and invasion, and angiogenesis. We further discuss the possibility of modulating SOCE or intervening in the downstream signaling pathways as a feasible targeting therapy for cancer treatment.

Efficacy and Safety of Endoscopic Nasopharyngectomy Combined With Low-Dose Radiotherapy for Primary T1-2 Nasopharyngeal Carcinoma.

AIM: Intensity-modulated radiotherapy (IMRT) is a widely accepted therapy for nasopharyngeal carcinoma (NPC), but it inevitably brings out radiation-related complications and seriously affects the quality of life (QoL). Endoscopic nasopharyngectomy (ENPG) has been successfully conducted in locally recurred NPC, but few studies evaluated its application in early NPC. This study aims to assess the feasibility and safety of ENPG combined with low-dose radiotherapy (LDRT) in T1-2 NPC. PATIENTS AND METHODS: We recruited 37 newly diagnosed localized T1-2 NPC patients who voluntarily accepted ENPG +LDRT from June 2013 to September 2016. Meanwhile, the data of 132 T1-2 NPC patients treated with IMRT were collected and used as control group. The survival outcomes, QoL score and late RT-related sequelaes were compared between the 2 groups. RESULTS: After a median follow-up of 54 months, only 1 patient in ENPG+LDRT group died along with hepatic metastases. The 5-year overall survival, distant metastasis-free survival, local relapse-free survival and regional relapse-free survival in ENPG+LDRT group were 97.3%, 97.3%, 100% and 100%, which were not statistically different from the control group (97.7%, 90.2%, 95. 5%, 97.0%, respectively, all P > 0.05). In comparison with IMRT group, ENPG+LDRT exhibited better QoL and less rate of late RT-related sequlaes including hearing loss (53.8% vs 27.0%, P = 0.005), xerostomia (46.2% vs 24.3%, P = 0.023) and dysphagia (25.8% vs 8.1%, P = 0.024). CONCLUSIONS: ENPG+LDRT provided satisfactory survival outcomes, and improved the QoL and reduced the incidence of sequelae for T1-2 NPC patients.

Effects of Surgery Combined with Chemoradiotherapy on Short- and Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma.

OBJECTIVE: The efficacy of surgery as the primary treatment modality for nasopharyngeal carcinoma (NPC) is yet to be clarified. Therefore, we aimed to explore the short- and long-term efficacy of surgery for early-stage NPC. METHODS: We retrospectively evaluated 341 patients diagnosed with early-stage NPC between September 2010 and December 2015. Among them, 58 patients underwent endoscopic nasopharyngectomy combined with chemoradiotherapy, whereas 283 patients underwent conventional chemoradiotherapy. The patients who underwent concurrent chemoradiotherapy or radiotherapy alone were matched to patients who underwent surgery in a 1:2 ratio using propensity score matching to analyze the clinical efficacy of each therapeutic modality. The primary endpoint was survival, and the secondary endpoints were tumor regression rate and reduction in Epstein-Barr virus (EBV)-DNA levels. RESULTS: After matching, 156 patients were enrolled (58 patients in the surgery group; 98 patients in the non-surgery group). The baseline data of the matched patients had good inter-group comparability (All P>0.05). The surgery group had significantly higher 5-year overall survival (98.30% vs. 91.70%), disease-free survival (98.30% vs. 81.40%), and recurrence-free survival (100.00% vs. 90.10%) rates than did the non-surgery group (All P<0.05). In total, 0 and 14 patients in the surgery and non-surgery groups, respectively, had residual cancer at the end of treatment (P=0.001). All patients in the surgery group tested negative for EBV-DNA, whereas two patients in the non-surgery group tested positive. The incidence of hematologic toxicity during treatment was similar between the two groups (All P>0.05). Still, the incidence of severe oral mucositis was lower in the surgery group than in the non-surgery group (37.9% vs. 54.08%, P=0.051). CONCLUSION: Surgery can improve the clearance rate of EB virus and reduce tumor residue. Surgery may be a safe and effective treatment for early NPC.

EB virus promotes metastatic potential by boosting STIM1-dependent Ca2+ signaling in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a unique head and neck malignancy with highly metastatic cell-biological characteristics, for which latent EBV-infection is responsible. Our earlier studies showed that EGF-stimulated Ca2+ signaling via store-operated Ca2+ entry (SOCE) was amplified in NPC cells expressing EBV-encoded LMP1, thus contributing to EBV-enhanced metastatic capacities. However, the pathway through which EBV modulates cytosolic Ca2+ signaling still remains unclear. Here, we demonstrated that EBV-infection amplified EGF-stimulated Ca2+ responses through the promotion of intracellular aggregation of STIM1, which serves as a Ca2+ sensor to activate SOCE. Blockage of EBV-remodeled Ca2+ signaling by STIM1-silencing inhibited cell migration by interrupting epithelial-mesenchymal transition (EMT) in vitro, and suppressed tumor dissemination in zebrafish and lymph node metastasis in mice. In addition, STIM1 expression was upregulated in primary NPC tissues compared with normal nasopharyngeal epithelium and stronger among the patients with advanced lymph node metastatic disease (N2-3 stage). Our findings thus indicate that EBV promotes metastatic potential by enhancing STIM1-dependent Ca2+ signaling that manipulates EMT in NPC cells. EBV-modulated Ca2+ signaling could serve as a candidate anti-metastatic target for NPC treatment.

Clinical outcomes of patients with nasopharyngeal carcinoma treated with antibiotics for radiation-induced mucositis: a retrospective study.

OBJECTIVE: To examine the effects of antibiotic administration on radiation-induced oral and oropharyngeal mucositis, and on the prognosis of patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively analyzed data for patients with NPC with grade 1/2 or 3/4 mucositis. Forty-two patients with grade 3/4 mucositis received antibiotics. Univariate survival analysis was assessed by Kaplan-Meier survival curves, survival curves were compared using log-rank tests, and multivariate analysis was carried out by Cox regression. RESULTS: A total of 463 patients with NPC were included in the study (194 grade 1/2 mucositis, 269 grade 3/4 mucositis). Univariate analyses identified T-stage, N-stage, clinical stage, type of treatment, and antibiotic use as factors affecting overall and disease-free survival. Multivariate analysis also determined that T-stage, N-stage stage, type of treatment, and antibiotic usage were independent factors affecting overall and disease-free survival. Mucositis improved in 32 of the 42 patients who received antibiotics (76.19%). However, red blood cell count and hemoglobin levels decreased in all patients after antibiotic treatment. CONCLUSIONS: Antibiotics may be effective for the treatment of severe radiation-induced mucositis (grade 3/4) during chemoradiotherapy, but may potentially adversely affect the prognosis of patients with NPC.

Effects of hepatitis B virus infection and antiviral therapy on the clinical prognosis of nasopharyngeal carcinoma.

PURPOSE: To investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis. METHODS: We conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow-ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS: Among the 876 participants, 106 (12.1%) patients were HBV-infected patients. The hepatitis B surface antigen-positive [HBsAg(+)] group had a lower CD4+ T cell count than the HBsAg(-) group (P = .048). Among patients with stage I/II NPC, 5-year overall survival (OS), disease-free survival (DFS), relapse-free survival, and distant metastasis-free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(-) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P = .017, .018, and .004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5-year DMFS existed between the antivirus (90.0%) and no-antivirus groups (70.0%) (P = .043). CONCLUSIONS: Hepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(-) group. Anti-HBV treatment may improve the prognosis of HBV-infected NPC patients.

Long Noncoding RNAs and Messenger RNAs Expression Profiles Potentially Regulated by ZBTB7A in Nasopharyngeal Carcinoma.

Our previous studies showed that ZBTB7A played an important role in promoting nasopharyngeal carcinoma (NPC) progression. However, molecular mechanisms of different levels of ZBTB7A are still unclear. It is necessary to search molecular markers which are closely connected with ZBTB7A. We selected NPC sublines CNE2 with stably transfecting empty plasmid (negative control, NC) and short hair RNA (shRNA) plasmid targeting ZBTB7A as research objectives. Microarray was used to screen differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) via shRNA-CNE2 versus NC-CNE2. Quantitative PCR (qPCR) was used to validate lncRNAs and mRNAs from the sublines, chronic rhinitis, and NPC tissues. Bioinformatics was used to analyze regulatory pathways which were connected with ZBTB7A. The 1501 lncRNAs (long noncoding RNAs) and 1275 differentially expressed mRNAs were upregulated or downregulated over 2-fold. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the upregulated or downregulated carbohydrate and lipid metabolisms probably involved in carcinogenicity of shRNA-CNE2 (P-value cut-off was 0.05). In order to find the molecular mechanisms of ZBTB7A, we validated 12 differentially expressed lncRNAs and their nearby mRNAs by qPCR. Most of the differentially expressed mRNAs are closely connected with carbohydrate and lipid metabolisms in multiply cancers. Furthermore, part of them were validated in NPC and rhinitis tissues by qPCR. As a result, NR_047538, ENST00000442852, and fatty acid synthase (FASN) were closely associated with NPC. ZBTB7A had a positive association with NR_047538 and negative associations with ENST00000442852 and FASN. The results probably provide novel candidate biomarkers for NPC progression with different levels of ZBTB7A.

A study on the value of narrow-band imaging (NBI) for the general investigation of a high-risk population of nasopharyngeal carcinoma (NPC).

BACKGROUND: This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients. METHODS: The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated. RESULTS: A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = - 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode. CONCLUSION: NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

Clinical outcomes of residual or recurrent nasopharyngeal carcinoma treated with endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy alone: a retrospective study.

BACKGROUND: Local residual and recurrent nasopharyngeal carcinoma (NPC) generally shows treatment failure after standard radiotherapy with or without concurrent chemotherapy. Whether endoscopic nasopharyngectomy might provide an additional therapeutic advantage remains controversial. Therefore, we retrospectively compared the clinical prognoses of patients with residual or recurrent NPC treated with endoscopic nasopharyngectomy combined with chemoradiotherapy (CRT) with those of patients treated with CRT alone. METHODS AND MATERIALS: A total of sixty-two patients with local residual or recurrent NPC were studied retrospectively: 36 patients received endoscopic nasopharyngectomy combined with CRT, whereas 26 patients who refused the surgery or had surgical contraindications received CRT alone. Serum Epstein-Barr virus (EBV) DNA levels were measured pre- and post-treatment. The differences in prognosis between the two treatment regimens and the pre- and post-treatment changes in EBV-DNA levels were analyzed. RESULTS: The median follow-up time was 31 months, with a 3-year overall survival (OS) of 51.40% and a 3-year disease-free survival (DFS) of 46.86%. The surgery + CRT group had a better OS than the CRT alone group did (χ2 = 4.054, P = 0.044). The pretreatment EBV-DNA levels showed a positive correlation with the clinical staging of recurrent NPC (χ2 = 11.674, P = 0.009). Patients with negative pretreatment serum EBV-DNA levels showed a superior OS to those of patients who tested positive for EBV-DNA (>0 copy/mL) (χ2 = 9.833, P = 0.002). The post-treatment EBV-DNA levels, compared with the pretreatment levels, decreased significantly in the surgery + CRT group (Z =  - 3.484, P = 0.000). In contrast, the EBV-DNA levels after CRT alone did not decrease significantly (Z =  - 1.956, P = 0.051). Multivariate analysis indicated that local staging, pretreatment EBV-DNA load, and the treatment method were independent risk factors for OS. Subgroup analysis indicated that the patients who tested negative for EBV-DNA before the treatment and those who received surgery + CRT showed a better OS than those who received CRT alone. CONCLUSIONS: The pretreatment serum EBV-DNA level was associated with disease prognosis. The combination therapy preceded by surgery can effectively decrease the copy number of EBV-DNA. Patients with local intermediate- and late-stage NPC, especially those negative for EBV-DNA, may consider opting for surgery followed by post-operative adjuvant radiotherapy or chemotherapy.

Influence of endoscopic sinus surgery on the quality of life of patients with early nasopharyngeal carcinoma and the analysis of prognosis-related factors.

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ2 = 4.403, p = 0.036; χ2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.

[A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAA receptors].

The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABAA and NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.