Targeting EZH2 depletes LMP1-induced activated regulatory T cells enhancing antitumor immunity in nasopharyngeal carcinoma

Objective: Regulatory T cells (Tregs) are critical factors that impair antitumor immunity. Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is one of the most pathogenic factors in nasopharyngeal carcinoma (NPC). However, the role of EBV-encoded LMP1 in regulating Treg generation in NPC remains unclear. Materials and Methods: The in vitro stability of activated Tregs (aTregs) influenced by LMP1 was analyzed by flow cytometry. The inhibitory effects of LMP1-HONE1 antigen-induced aTregs on tumor-associated antigen (TAA)-specific T cells were analyzed in vitro and in vivo. Finally, the expression of LMP1, Foxp3, and enhancer of zeste homolog 2 (EZH2) were analyzed in samples from 86 NPC patients by immunohistochemistry and immunofluorescence. Results: LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. EZH2 inhibitor, DZnep, depleted LMP1-HONE1 antigen-induced aTregs in vitro and led to potent TAA-specific T cell antitumor immunity in vivo. In NPC tissues, LMP1 expression level was positively correlated with the number of EZH2+ Tregs, which was positively correlated with clinical stage and overall survival. Conclusions: EZH2 is essential for maintaining the stability and inhibitory functions of aTregs that are induced by EBV-encoded LMP1 in NPC

Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.

Lateral endoscopic transorbital approach to middle skull base: anatomical and surgical practice study / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the anatomical and surgical approaches to middle cranial fossa through orbital lateral wall under endoscope.@*Methods@#Cadaveric formalin fixed specimens and fresh colored silicone injected specimens were used for this study. All anatomic technical measurements were performed under 0° and 30° endoscope and infrared rays navigation. The surgical approach was designed with the bony opening on the lateral wall of orbit through which the lateral side of the middle cranial fossa could be directly entered under endoscope. One case of recurrent meningioma was performed through this surgical approach. SPSS 20.0 software was used for statistical analysis.@*Results@#The approach can directly enter the middle cranial fossa and expose anatomic landmarks including superior orbital fissure, lateral side of cavernous sinus, foramen rotundum, foramen ovale, foramen spinosum, petrosal bone and others as well as Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅵ cranial nerves under endoscope. The maximal bony opening through the lateral wall of orbit was measured, with a horizontal diameter of (1.38±0.68) cm, a vertical diameter of (2.02±0.32) cm, a depth of (1.44±0.42) cm from bony opening margin to the dura. The recurrent meningioma involving lateral side of the middle skull base was successfully removed by this surgical approach through lateral wall of orbit.@*Conclusion@#Lateral transorbital endoscopic approach to the lateral side of middle skull base is a safe, feasible, and minimally invasive method, which allows surgeons to directly manipulate diseases involving this area with good visualization and minimal invasion under endoscope.

Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2–3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.

Clinical application of supraclavicular flap for oncologic reconstruction of hypopharynx and upper esophagus / 中华耳鼻咽喉头颈外科杂志

Objective@#To assess the efficacy of supraclavicular artery island flap (SCAIF) for the reconstruction of hypopharynx and upper esophagus.@*Methods@#The SCAIF procedure on was used in 10 patients, including 8 with hypopharygeal carcinomas, 1 with esophageal carcinoma and neck skin invasion and 1 with hypopharyngeal leiomyosarcoma, at the Otorhinolaryngology Hospital, the First Affiliated Hospital, Sun Yatsen University between December 2015 and June 2017. The sizes of the flaps were measured in (4-8) cm×(5-12) cm. Clinical indexes such as harvesting time and survival were recorded.@*Results@#Harvesting time for SCAIF ranged from 20 to 30 minutes, averaging 26 minutes. Nine flaps survived, one flap had partially necrosis. Functional outcomes were excellent and the donor sites were direct closed without complications.@*Conclusions@#SCAIF is a versatile, reliable, and easily harvested flap, with good cosmetic and functional outcomes for reconstructing the defects of hypopharynx and upper esophagus.

Immunoregulatory role of tolerogenic dendritic cells in allergic rhinitis in mice / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the immunoregulatory role of tolerogenic dendritic cells(TolDC) in allergic airway inflammation in mouse model of allergic rhinitis(AR).METHODS A total of 24 Balb/c mice were equally and randomly divided into 4 groups with 6 mice in each group. AR group was established with oval bumin(OVA) sensitization and challenge, meanwhile the physiological saline(PBS) sensitization and challenge as the control group. AR group were treated by adoptive transfer of TolDC as treatment group. And treatment group were injected intraperitoneally with TGF-β/IL-10R neutralizing antibody as blockade group. In each group, allergic nasal symptoms score, inflammatory cell infiltration in lung, the expression of Th1/Th2-derived cytokines in the bronchoalveolar lavage fluid(BALF) and nasal lavage fluid(NALF), the expression of OVA-specific serum IgE and the expression of Treg in lung were measured.RESULTS The mouse model of OVA-induced AR was successfully developed. Compared with AR group, treatment group exhibited lower allergic nasal symptoms score, a decrease in inflammatory cell infiltration in lung, lower expression of Th1/Th2-derived cytokines in BALF and NALF and OVA-specific serum IgE, as well as up-regulation of Treg in lung, which were abolished by TGF-β/IL-10 neutralizing antibody shown in blockade group.CONCLUSION TolDC suppress airway inflammation in AR by inducing regulatory T cells through TGF-β/IL-10-dependent mechanisms.

Expression of heme oxygenase-1 in nasal polyps and regulation by glucocorticoid / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the expression and possible modulation of heme oxygenase-1 (HO-1) in nasal polyps of patients with chronic rhinosinusitis with nasal polyps (CRSwNP).</p><p><b>METHODS</b>Nasal polyps and uncinate process tissues were collected from 25 CRSwNP patients and 19 healthy controls with nasal septal deviation. HO-1 expression was examined using qRT-PCR, immunohistochemistric staining and Western blot analysis. Moreover, additional uncinate process mucosal samples of 15 healthy controls with nasal septal deviation were harvested for nasal explant culture experiments. HO-1 expression was measured in cultured nasal explant in response to specific inflammatory and glucocorticoid stimulation. SPSS 20.0 software was used to analyze the data.</p><p><b>RESULTS</b>The mRNA and protein expression of HO-1 was significantly increased in polyp tissues, 1.220±0.397 in mRNA and 1.409±0.701 in protein, compared with healthy controls 0.464±0.318 in mRNA and 0.017±0.1147 in protein (U=22.00 in mRNA and U=1.00 in protein, both P< 0.05). The immunohistochemical results showed that HO-1 was mainly distributed in the epithelial layer, submucosal glands and inflammatory cells in nasal tissues. Nasal explant culture experiments demonstrated that HO-1 mRNA was upregulated by IL-17A. The HO-1 mRNA level before the stimulation was 1.000, and 17.264±4.275 after the stimulation of 1 ng/ml IL-17A (U=0, P<0.05), 19.128±4.605 after the stimulation of 10 ng/ml IL-17A (U=0, P<0.05), but was significantly suppressed after stimulation with glucocorticoids (dexamethasone, DEX). The mRNA level after the glucocorticoids stimulation was 0.370±0.101 (U=0, P<0.05) and 0.316±0.167 (U=0, P<0.05) respectively. Furthermore, the HO-1 mRNA was inhibited by TGF-β1, the mRNA level was 0.217±0.322 (U=0, P<0.05), 0.070±0.070 (U=0, P<0.05), respectively.</p><p><b>CONCLUSION</b>Increased HO-1 expression may play a role in the pathogenesis of CRSwNP, which may be considered as the therapeutic target.</p>

Inhibition of miR-9 expression suppresses proliferation, invasion and mi-gration of nasopharyngeal carcinoma cells / 中国病理生理杂志

AIM:To investigate the effects of down-regulated miR-9 expression on the proliferation , invasion and migration of nasopharyngeal carcinoma (NPC) cells.METHODS:Human NPC CNE1 and CNE2 cells were transfect-ed with the inhibitor of miR-9 by Lipofectamine to down-regulate the expression of miR-9, and the cells transfected with an inhibitor control were also set up .The cell proliferation and cell cycle were evaluated by CCK-8 assay and flow cytometry . The cell invasion and migration abilities were detected by Transwell invasion and wound -healing assays .Immunoblotting was applied to analyze the levels of the proteins .RESULTS:Compared with control group , inhibition of miR-9 expression in the NPC cells by transfection of the miR-9 inhibitor significantly decreased the proliferation ability (P<0.05).The per-centages of the cells in G 0/G1 phase [ CNE2: ( 57.96 ±1.39 )% vs ( 47.93 ±1.76 )%, P<0.05; CNE1: ( 51.24 ± 0.88)%vs (48.29 ±0.39)%, P<0.05] were significantly increased.The migration distances [CNE2: (186.50 ± 7.94)μm vs (247.56 ±15.56)μm, P<0.05;CNE1:(139.06 ±16.73)μm vs (230.66 ±14.27)μm, P<0.01] and the invasion ability of the CNE2 cells (43.00 ±3.17 vs 65.80 ±5.20, P<0.01) were also significantly inhibited .Moreo-ver, the tumor cells transfected with the inhibitors produced lower β-catenin.CONCLUSION:Inhibition of miR-9 expres-sion suppresses the proliferation , invasion and migration of nasopharyngeal carcinoma cells .

Questionnaire survey on obstructive sleep apnea hypoventilation syndrome and related complications / 中华全科医师杂志

Objective To investigate relationship between obstructive sleep apnea hypoventilation syndrome(OSAHS) and hypertension.Methods Questionnaire survey was conducted among 1573 local permanent residents in Guangzhou during March and June 2006 to understand prevalence of hypertension and snoring,and polysomnography monitoring was performed for 347 of them with moderate and severe snoring to estimate prevalence of OSAHS.Risk factors for hypertension was screened with multivariate logistic regression analysis.Results In total,1547 copies of valid questionnaires were collected,and 184 cases (11.9%) of hypertension were found with a prevalence of 10Department of Endocrinology,Shanxi Provincial People's Hospital,Taiyuan 030012,China 0%,49 of diabetes with a prevalence of 2.7%,and 212 of dyslipidemia with a prevalence of 10.4%.Prevalence of OSAHS was found in 34 of them (2.2% ) with Epworth sleepiness scale (ESS) score equal to or greater than nine.Prevalence of hypertension in OSAHS group was 32.5%,much higher than that in non-snoring group (8.3% ) and snoring group ( 17.1% ).Results of logistic regression analysis showed that age,gender,OSAHS,diabetes and dyslipidemia all were high-risk factors for hypertension,with OSAHS ranking the third.Conclusion OSAHS is one of high-risk factors for hypertension.

Kinetic expression of T-bet and GATA-3 genes in rat allergic rhinitis models / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate kinetic expression of genes T-bet and GATA-3 in blood mononuclear cells (BMCs) in allergic rhinitis rats model at different stages of development of allergic rhinitis.@*METHOD@#Twenty SD rats (including 10 male and 10 female) were divided into 2 groups, experimental group and control group, randomly, 10 rats for each group. Ten rats in experimental group were sensitized and intranasally challenged by OVA, aluminium hydroxide hydrate gel and Bordelella pertussis inactive microorganism suspension (B. pertussis) adjuvants, as allergic rhinitis models, Ten rats in control group were investigated using physiological saline only. BMCs were separated from 2 ml blood which was extracted from rat heart at the end of sensitization, 10- hour after the first challenge and 10-hour after the final challenge, respectively. RT-PCR was utilized to detect the expression of T-bet and GATA-3.@*RESULT@#At the end of sensitization, 10-hour after the first challenge and 10-hour after the final challenge, in experimental group, Relative quantitation of expression of T-bet was 0.404 +/- 0.187, 1.676 +/- 0.708, 0.503 +/- 0.514 and that of GATA-3 was 0.434 +/- 0.147, 0.600 +/- 0.480, 1.029 +/- 0.690, respectively. While, In control group, Relative quantitation of expression of T-bet was 0.487 +/- 0.212, 0.486 +/- 0.148, 0.495 +/- 0.103 and and its of GATA-3 was 0.596 +/- 0.249, 0.474 +/- 0.101, 0.550 +/- 0.119, respectively. At 10-hour after the first challenge, relative quantitation of expression of T-bet in experimental group was increased markedly and there was significant difference compared with contol group (t=4.18, P<0.01). In experimental group, The amount of expression of T-bet at 10-hour after first challenge was higher than it at 10-hour after the final challenge and there was markedly difference (t=5.14, P<0.01). The amount of expression of T-bet at 10-hour after first challenge was increased significantly compared with it at the end of sensitization (t= 5.27, P<0.01). while, the expression of GATA-3 at 10-hour after final challenge was markedly increased compared with it at the end of sensitization (t= 3.51, P<0.05) and was higher than it at 10-hour after first challenge (t=2.53, P<0.05). At 10-hour after final challenge, The amount of expression of GATA-3 in experimental group was significantly higher than it in control group (t=2.71, P<0.05). However, both the expression of GATA-3 and T-bet had not markedly changed in control group.@*CONCLUSION@#It is thought that the development of allergic rhinitis is a successive and sequencing kinetic course, and imbalance of expression of GATA-3 and T-bet may be genetic base on allergic rhinitis, both GATA-3 and T-bet were involved in allergic rhinitis only in different phase of development of allergic rhinitis.

Diagnosis of small round cell tumor of nasal sinus and bases of skull (a report of 123 cases) / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the features and diagnosis way of small round cell tumor of nasal sinus and bases of skull.@*METHOD@#A retrospective analysis of 123 case with small round cell tumor of nasal sinus and bases of skull were carried out in our hospital in past ten year. Clinical, histological, radiological and immunohistochemical characters of these cases were studied.@*RESULT@#All cases usually complained of nasal obstruction, headache, diplopia, nasal mucus with bleeding, vision or weight loss. Expansible or infiltrative lumps were found in nasal sinus or bases of skull in radiological examination. A lot of small round cells were found in these tumors in histological pathology. At least 5-6 cell, tissue or tumor markers were examined immunohistochemically in most of cases before the final diagnosis were made. In some cases over 20 markers were examined. Five cases were carried out transmission electron microscope examination, special features such as desmosome and myofilament were found.@*CONCLUSION@#Clinical symptom, physical signs and radiological finding can supply malignant evidences of these tumors. Histological examination can make certain that they are small round cell tumors, but final diagnosis is still hard to make only by these. Immunohistochemical examination of various markers can tell the original characters of the specimen tissues, it is the key for final diagnosis. Transmission electron microscope examination is another helpful way for diagnosis.

Clinical study on aggressive rhinocerebral mucormycosis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the clinical diagnosis, course and combined therapy of aggressive rhinocerebral mucormycosis.@*METHOD@#The clinical feature, diagnosis and therapy were analyzed in 5 cases with rhinocerebral mucormycosis throughout disease progress. Good treatments were found by analyzing curative effect of different treatment.@*RESULT@#One patient died within three weeks in hospital three patients survived from 2 months to 2 years; and one patient was alive over 3 years. The mortality rate was 80% in this study.@*CONCLUSION@#Rhinocerebral mucormycosis is always secondary to patients with severe diseases and bad immunologic function. The lesion can invade the orbit and brain quickly, and the mortality rate is high. The cause of the disease can be retarded by clearing up the focus early and removing the environment of fungi thriving with combined therapy. It is effective of remodelling the necrotic tissues by nasal endoscopy.

Clinical outcome of conservative treatment for pharyngocutaneous fistula / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the conservative management and outcomes of pharyngocutaneous fistula after total laryngectomy.@*METHOD@#Twenty-one patients with postoperative fistulas were identified and treated by conservative therapy.@*RESULT@#Different treatment were given basing on the three stages of pharyngocutaneous fistula: drainage and cleaning stage, pressure bandaging stage and healing stage. Fourteen patients (66.7%) with the conservative therapy resumed oral feeding after closure of fistula, the other 7 patients had to be cured by further operation.@*CONCLUSION@#Management basing on the stages of pharyngocutaneous fistula can achieve satisfied outcome. It can provide important information for pharyngocutaneous fistula's treatment.

Expression of T-bet in nasopharyngeal associated lymphatic tissue of patients with allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the pattern and value of the expression of T-bet in nasopharyngeal-associated lymphatic tissue (NALT) of patients with or without allergic rhinitis (AR).@*METHOD@#T-bet and CD4/T-bet expression in adenoids, tonsils and nasal mucosa was respectively detected with single stain and double stain of immunohistochemistry.@*RESULT@#The positive ratio of T-bet expression in tonsils, adenoids and nasal mucosa between AR group and the control group had statistically different (P < 0.05). There was statistical difference of T-bet expression in tonsils from AR group in three different age groups (P < 0.05). The difference was that T-bet expression in adults group was significantly lower than that in children group and adolescent group. There was no difference of T-bet expression among different age groups in non-AR group. There were some positive expression of CD4 and T-bet in tonsils, adenoids and nasal mucosa from two groups and most positive expression of T-bet on CD4 positive cell.@*CONCLUSION@#T-bet expression was down-regulated in NALT of patients with AR. T-bet expression of NALT is associated with allergic mucosal inflammation and functional status of NALT, as well as the weak Th1 response at the level of transfer factor in local mucosa of respiratory tract in AR patients.

Expression and significance of PCNA and p27 in inverted papilloma of nasal cavities and paranasal sinuses / 中国耳鼻咽喉头颈外科

0.05). CONCLUSION The PCNA labeling index may reflect the proliferating condition of NIP, but does not have relationship with NIP recurrence. And the role of p27 in the development of NIP needs more investigation.

Effect of OSAHS on children growth and their clinical features / 中国耳鼻咽喉头颈外科

0.05). CONCLUSION Obesity was an influential factor of snoring. The PS and OSAHS have the same effect on children growth and their clinical features.

Quality of life in laryngectomees and its influencing factors in Guangdong and Hong Kong / 中国耳鼻咽喉头颈外科

OBJECTIVE To summarize the clinical experience of endoscopic thyroidectomy via suprasternal approach. METHODS Endoscopic thyroidectomy via suprasternal approach was performed in 35 patients with ultrasonic scalpel. RESULTS Operations were successfully performed in 35 patients. The mean operation times were 130 (105～190) minutes in 24 cases with subtotal lobectomy and 4 case with total lobectomy, 60 (50~70) minutes in 2 cases with isthmectomy, 228 (185～270) minutes in 2 case with bilateral subtotal lobectomy, 163 (140～215) minutes in 3 case with subtotal lobectomy and the contralateral ademona resection. The bleeding during operation was 5 to 40ml and the average hospital stay time was 4 (3～5) days. CONCLUSION Endoscopic thyroidectomy via suprasternal approach is a safe way with good cosmetic value.

Evaluation the adenoid and tonsil in children with obstructive sleep apnea hypopnea syndrome / 中国耳鼻咽喉头颈外科

0.05),but there was a significant difference in the lowest SaO2,average SaO2 and AHI between the 2 groups(P

Expression of T-bet in peripheral blood and its relation with serum IgE in patient with allergic rhinitis / 免疫学杂志

Objective To investigate T-bet mRNA expression on peripheral blood mononuclear cells (PBMCs) and its relations with allergen specific IgE (SIgE), eosinophile cationic protein (ECP) levels, and allergic symptom in patients with allergic rhinitis (AR). Methods The allergen, SIgE, and ECP in serum of patients with AR were detected by Unicap CAP system. Blood samples were taken from 15 healthy controls and 35 house dust mite allergic patients. PBMC was isolated by density gradient centrifugation and one part of them was cultured with mite allergen at a concentration of 50 μg/mL. PBMC was subjected to analysis of T-bet mRNA expression using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results The ratio of T-bet to β-actin mRNA levels was 0.418 ± 0. 101 in patients of AR and 0.706 ± 0.091 in healthy controls and the difference was significant (P ＜ 0.01). The expression intensity of T-bet mRNA was not related to varying severity of allergic symptom and ECP levels ( r = - 0.227, - 0.033, P ＞ 0.05). However, there was an inverse correlation between expression intensity of T-bet mRNA and SIgE concentration (r = -0.375, P ＜ 0.05). There was a positive correlation between SIgE and allergic symptom scores ( r = 0.426, P ＜ 0.05). After that PBMC was stimulated by mite allergen, the expression intensity of T-bet mRNA, ECP, and SIgE changed very little ( P ＞ 0.05). Conclusion Down-regulated expression of T-bet mRNA in mite-AR patients is not related to serum ECP and symptom scores but one of important links in the mechanism of imbalance of Th1/Th2 in the occurrence of AR. Specific allergen has no effect on T-bet mRNA, ECP, and SIgE of children and adults with AR in vitro. The level of SIgE objectively and directly indicates the severity of allergic symptom, but T-bet did not. T-bet may be one of indirect factors which affect the level of IgE.