[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[The progress of voice restoration after total laryngectomy].

Total laryngectomy or laryngopharyngectomy is the main treatment strategy of choice for advanced laryngeal/hypopharyngeal carcinoma.However,the operation is associated with important consequences over and above the loss of normal voice.Therefore,it is necessary toachieve voice in the absence of a functional larynx.The objective of this article is to provide an over view of current methods and a summary of the present progress about voice rehabilitation after total laryngectomy.

[Nasopharyngeal low grade papillary adenocarcinoma with squamous differentiation：a case report].

Summary Low grade papillary adenocarcinoma is especially rare tumor in nasopharynx. Here we reported a patient who had low grade papillary adenocarcinoma of the nasopharynx and was diagnosed by pathology. The patient complained for bilateral nasal congestion for 10 years and was hospitalized in recent 3 years. The patient received nasopharyngeal tumor resection, and the postoperative pathological examination showed low grade nasopharyngeal papillary adenocarcinoma with squamation. The patient was followed up for 9 months without recurrence or metastasis. We reported this case and reviewed the relevant literature in order to improve the diagnosis and treatment of this disease..

[Clinicopathological characteristics and prognosis of diffuse midline gliomas with histone H3K27M mutation: an analysis of 30 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

[The roles of sodium-glucose transporters in tumor cell energy metabolism].

Glucose is a major metabolic substrate required for cancer cell survival and growth.Instead, the entry of glucose molecules into the cells is effected by a large family of structurally related transport proteins known as glucose transporters. Two main types of glucose transporters have been identified, namely, the passive facilitative glucose transporters(GLUTs) and the secondary active sodium-coupled glucose transporters(SGLTs).However, tumor cells may adapt to an ischemic microenvironment by upregulation of SGLTs in the plasma membrane which supplies the tumor cell with glucose even at very low extracellular glucose concentration.Therefore, SGLTs is essential for ischemic and hypoxic tumor cells to uptake glucose.Current research indicates that SGLTs may become a promising biomarker for cancer therapy.

[A preliminary study on the relationship between GLUT-1，MCT-4 and CA⠨ in laryngeal squamous cell carcinoma].

Objective:The aim of this study was to evaluate the expression of metabolism-related proteins including glucose transporter-1(Glut-1), monocarboxylate transporter-4 (MCT-4) and carbonic anhydrase Ⅸ (CAⅨ) in laryngeal squamous cell carcinoma and to access the clinical significance of the results.Method:Forty cases of laryngeal squamous cell carcinoma and 10 cases of adjacent corresponding laryngeal mucosal tissues was selected. Histopathological grading, TNM and staging were done. Immunohistochemical staining for GLUT-1, MCT-4 and CAIX was performed on tissue sections from 40 cases of laryngeal squamous cell carcinoma and 10 cases of adjacent corresponding laryngeal mucosal tissues to evaluate the association between the expression of metabolism-related proteins and clinicopathologic factors. Analysis was performed on SPSS software (Windows version 21.0). Result:The positive expression of GLUT-1，MCT-4 and CAⅨ in the 40 cases of laryngeal carcinoma was 72.5%，75% and 55% respectively. MCT-4 expression in normal mucosa was minimal or absent，while，the basal layer of proliferating stem cells is highly enriched in GLUT-1. Significant association of GLUT-1，MCT-4 and CAⅨpositive expression was found with histologic grade（P=0.012，P=0.028,P=0.013）, which high poorly differentiated expression in LSCC as compared to the well differentiated carcinoma cells. Moreover, of the 40 cases of LSCC，MCT-4 and CAⅨ was significantly associated with TNM stage(P=0.016，P=0.005). Higher MCT-4 and CAⅨ in stage Ⅲ or Ⅳ was found as compared to stageⅠor Ⅱ. The expression of GLUT-1，MCT-4 and CAIX showed no relationship with age，smoking amount，lymphnode metastasis or the tumor location（P>0.05）. There were significant positive correlations between the expression of GLUT-1, CAⅨ and tumoral expression of MCT-4(P<0.05) . Conclusion:The results here in presented glocuse uptake and pH regulation are closely linked in the metabolic remodeling，cancer progression and aggressiveness in LSCC. Therefore, combinatorial targeting of the metabolism-related proteins in the microenvironment of hypoxia may be an effective strategy for the treatment of patients with aggressive cancer.

[Study on the relationship between MCT-1 and p53 in laryngeal squamous cell carcinoma].

Objective:The aim of this study is to investigate the expression and clinical significance of monocarboxylate transporter 1 (MCT-1) and p53 in laryngeal squamous cell carcinoma (LSCC). Method:Immunohistochemical staining of MCT-1 and p53 was carried out in 41 cases of laryngeal squamous cell carcinoma embedded in paraffin, and the relationship between positive expression and clinicopathological data was evaluated. All data were analyzed by SPSS software (Windows version 21.0). Result:In normal mucosa p53 expression was absent; while, the basal "stem cell" layer is highly enriched in MCT-1. The positive expression of MCT-1 and p53 in the 41 cases of LSCC was 73.2% and 61.0% respectively. The differential expressions of MCT-1 and p53 in LSCC and normal tissues had significant difference (P=0.002, P=0.028). In the well-differentiated tumor tissues, MCT-1 was mainly expressed in the highly invasive cancerous cells. In poorly differentiated tumors, cells in the nests diffusely stain strongly for MCT-1. Of the 41 cases of LSCC, MCT-1 and p53 was significantly associated with histologic grade (P=0.046, P=0.047), clinical stage (P=0.023, P=0.044) and lymph node metastasis (P=0.044, P=0.005). However, over expression of MCT-1 and p53 had no relation with age (P=0.945, P=0.364), gender (P=1.0, P=1.0) and tumor location (P=0.456, P=0.51). Spearman analysis is shown a positive correlation with MCT-1 and p53 (r=0.418, P=0.006). Conclusion:MCT-1 is an importer of L-lactate and ketone bodies into cells, and high expression of MCT-1 induces high OXPHOS and low glycolytic states. We show here that MCT-1 is the best marker of the basal stem cell layer of normal mucosa, and its expression correlate with high p53 expression in LSCC. Therefore, MCT-1 is a new target for the development of anticancer drugs for laryngeal squamous cell carcinoma.

[External nose eccrine poroma：a case report].

Eccrine poroma is a benign neoplasm of the terminal duct. It is commonly located in distal extremities but rarely present in head and neck. This report mainly describes a case of external nose eccrine poroma. We will clarify the disease from pathology; histopathological examination; diagnosis; clinical manifestations to prognosis.

[The relationship between ¹8F-FDG uptake and oncogene in human laryngeal squamous cell carcinoma transplantation tumor animal model].

Objective:The aim of this study is to explore the relationship between [F18] fluoro 2 deoxy d glucose ¹8F-FDG) uptake and oncogene expression in human laryngeal squamous cell carcinoma (LSCC) transplantation tumor.Method:Ten nude mice were randomly divided into two groups, 5 mice of each group. One group was injected subcutaneously with Hep-2 cells to establish xenograft model, and the other one was injected with HIF-RNAi-Hep-2 cells. All animals were conducted with positron emission tomography computed tomography PET scan. The average tumor T/N ratio was calculated. After PET scanning, tumor tissue was picked off for immunohistochemical examination.Result:The tumor imaging were both clear and there was no significant difference between these two groups (P> 0.05). The expression of hypoxia inducible factor 1 alpha (HIF-1α), glucose transporter protein-1 (GLUT-1) and vascular endothelial growth factor (VEGF) were high in Hep-2 group. The expression of HIF-1α was lower in HIF-RNAi-Hep-2 group (P< 0.05). But there was no significant difference about the expression of GLUT-1 and VEGF between these two groups (P> 0.05).Conclusion:The oncogenic pathway activated in LSCC is related with the uptake of ¹8F-FDG. The glycolysis gene and vascular factor maybe play a critical role.

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has become one of the most common forms of cancer worldwide. Hypermethylation-induced silencing of tumor-associated gene has been proposed as an important cofactor in cancer pathology. This paper aimed to characterize the gene methylation patterns in human papillomavirus (HPV) associated-HNSCC. TIMP3 and APC methylation status in neoplastic (N = 92) and non-neoplastic tissues (N = 92) of HNSCC as well as their association with HPV infection were investigated via methylation-specific PCR assays. Results indicated that methylation level of TIMP3 was markedly higher in HPV-positive tumors as compared with HPV-negative tumors. Both TIMP3 and APC methylation were associated with lymph node metastasis and higher clinical stage of tumors. Patients with methylation at TIMP3 or APC had worse prognoses as compared to those without these alterations. This is the first study that shows a possible linkage between HPV infection and APC methylation. Methylation patterns of tumor-related genes may contribute to different disease prognosis in HNSCC according to the HPV infection status.

[Research progress of Merlin protein and its signal pathway in tumor].

Hippo signaling pathway was first found in drosophila, and was proved to participate in regulatory of cell proliferation, cell apoptosis and organ size in multicellular animals. Compared with Hippo/Mst to YAP/Yki phosphorylation of the core kinase cascade, upstream the protein interaction of Hippo kinase cascade has rarely been studied. Early studies in drosophila have shown that apical membrane associated FERM domain protein Merlin and its extension may be upstream of the Hippo pathway as a signaling pathway component. Recently, increasing researches showed that Merlin protein has a close relationship with tumor occurrence. As upstream regulatory molecule and the core in Hippo signaling pathway, the mutation or deletion of Merlin can increase oncogene Yap/Yki expression, and then contribute to tumor progression. It ultimately affects the patients' prognosis. To clarify the relationship between Merlin(NF2) and malignant tumor will be helpful for the prevention and treatment of cancer. This article revivewed the latest research progress of Merlin(NF2) protein.