Homeobox B2 promotes malignant behavior and contributes to the radioresistance of nasopharyngeal carcinoma by regulating forkhead box protein O1.

Background: Nasopharyngeal carcinoma (NPC) is an epithelial tumor of the head and neck with heterogeneous racial and geographical distributions. Homeobox B2 (HOXB2) is a tumor promoter in many cancers. However, the biological role of HOXB2 in NPC has not been elucidated. Methods: Bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) between samples of patients with radiosensitive and radioresistant NPC. qRT-PCR, western blotting and immunohistochemistry were used to detect the expression levels of the corresponding mRNA and proteins. Cell viability was detected by CCK-8 assay and colony-forming capability was evaluated using colony formation assays. Further, migration and invasion abilities were examined using wound-healing and transwell chamber assays, respectively. Cellular apoptosis after irradiation was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Results: HOXB2 was identified as a potential regulator of radioresistance in NPC. Our in vitro results indicate that HOXB2 overexpression (HOXB2-OE) promoted malignant behaviors including invasion, migration, proliferation, and inhibited the irradiation-induced apoptosis of NPC cells. Consistent with these results, HOXB2 knockdown (HOXB2-sh) exhibited the opposite trends in these biological activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were enriched in the FOXO signaling pathway. Mechanistically, western blotting showed that HOXB2-OE inhibited forkhead box protein O1 (FOXO1) expression in NPC cells. Thereafter, we transferred the FOXO1-OE plasmid to HOXB2-OE NPC cells and found that overexpression of FOXO1 reversed cell proliferation, migration, invasion, and radioresistance profiles promoted by HOXB2 overexpression. Conclusion: Our findings showed that HOXB2 acts as a tumor promoter in NPC, activating malignant behaviors and radioresistance of tumors via FOXO1 regulation. Moreover, the inactivation of HOXB2 or activation of FOXO1 are potential strategies to inhibit tumor progression and overcome radioresistance in NPC.

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage.

Polyethyleneimine-polyethylene glycol (PEI-PEG), a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP) in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

[Effect of ossicular chain reconstruction with titanium ossicular replacement prosthesis in mastoidectomy with synchronous ossiculoplasty].

OBJECTIVE: To assess hearing effect of ossicular chain reconstruction with titanium ossicular replacement prosthesis during mastoidectomy with synchronous ossiculoplasty in chronic middle ear disease. METHOD: Retrospective reviews were performed for 139 patients who had underwent mastoidectomy and tympanoplasty with titanium ossicular replacement prostheses at the same time between 2008 and 2011. The partial ossicular replacement prostheses (PORP) were used in 91 patients and the total ossicular replacement prostheses (TORP) were used in 48 patients respectively. All patients had follow-up for 2 to 5 years. The preoperative and postoperative mean air conduction and air-bone gaps(ABG) for the four frequencies (0.5, 1.0, 2.0 and 4.0 kHz) were evaluated. The improvement of mean air conduction and ABG over the same frequencies were measured. A postoperative ABG less than or equal to 20 dB was considered a successful operation. The hearing results of titanium PORP and TORP were compared. RESULT: The mean air conductions were (53.97 +/- 11.32)dB and (36.80 +/- 11.68) dB preoperatively and postoperatively in PORP group. The mean improvement in air conduction was (17.17 +/- 5.79)dB. The mean ABG was (31.84 +/- 6.17)dB and (15.13 +/- 7.22)dB preoperatively and postoperatively in PORP group. The mean improvement in ABG was (17.71 +/- 5.5)dB. The difference of hearing threshold between preoperative and postoperative had statistical significance (P < 0.01). The mean air conduction were (58.05 +/- 11.35)dB and (44.53 +/- 13.15)dB preoperatively and postoperatively in TORP group. The mean improvement in air conduction was (13.52 +/- 7.81)dB. The mean ABG; were (35.67 +/- 5.73)dB and (21.48 +/- 7.01)dB preoperatively and postoperatively for TORP group. The mean improvement of hearing threshold in ABG was (14.18 +/- 7.53)dB. The difference of hearing threshold between preoperative and postoperative had statistical significance (P < 0.01). ABG less than 20 dB after operationwas happened in 68.63% of the patients (74.73% for PORP and 54.17% for TORP). There was statistically significant difference between PORP and TORP (P < 0.05). CONCLUSION: We conclude that titanium ossicular reconstruction during mastoidectomy with synchronous ossiculoplasty give stable and excellent hearing results. We obtained better results with PORP than with TORP.

[Application of ultracision-harmonic scalpel for tonsillectomy].

OBJECTIVE: To investigate the advantages and disadvantages of ultracision-harmonic scalpel assisted tonsillectomy by compared with conventional tonsillectomy. METHODS: Eighty-eight patients were randomly divided into ultrasonic scalpel group (group A, 42 cases) and control group (group B, 46 cases). The tonsillectomy in group A was performed with ultracision-harmonic scalpel, and in group B, the tonsillectomy was performed by routine method. The surgical time (complete removal of tonsils), blood loss, and postoperative sore throat situation were recorded. RESULTS: Surgical time in group A [(14.7 ± 4.0) min] was shorter than that in group B [(28.9 ± 7.6) min], t = -10.691, P < 0.05. Blood loss in group A [(3.1 ± 1.1) ml] was less than that in group B [(19.0 ± 5.2) ml], t = -19.544, P < 0.05. Postoperative sore throat was less painful in group A than that in group B in 10 hours after surgery, but much painful than group B 3 days after surgery and most patients lasted longer. There were statistical differences (P < 0.05). The average peel off time for the tunica albuginea was 8 days after the operation by using traditional method, by compared with the ultrasonic scalpel method, average time was 11 days, the difference showed statistical significance (t = 5.115, P < 0.05). CONCLUSIONS: Compared with traditional tonsillectomy, ultracision-harmonic scalpel tonsillectomy had shorter operative time, less blood loss and so on, but the sore throat symptoms persisted longer. In addition, the tunica albuginea peeled off later, so avoidance of secondary bleeding caused by improper diet was mandatory.

[Effect of brain-derived neurotrophic factor gene transfected bone-marrow mesenchymal stem cells on damaged cochlear spiral ganglion cells of guinea pigs].

OBJECTIVE: To investigate the protective role of brain-derived neurotrophic factor (BDNF) gene transfected bone-marrow mesenchymal stem cells (BMSC) on cochlear spiral ganglion cells (SGC) impaired by aminoglycoside antibiotics (AmAn). METHODS: The differentiation of BMSC transfected by BDNF gene (BDNF-BMSC) were detected with immunohistochemical examination of Nestin, neuron-specific enolase (NSE), and glial fibrillary acid protein (GFAP) antibody in vitro. BDNF gene transfected BMSC were transplanted into the cochleae of guinea pigs deafened by amikacin, while the control groups were designed in which artificial perilymphatic fluid (APF), BMSC or BDNF gene was injected into cochleae alone. The cochleae were obtained on the week 1, 2 and 4 after injection, respectively, paraffin-embedded, and cut in a paramodiolar plane subsequently. The histopathological changes of cochleae were observed, the density of SGC was calculated by staining with HE, and the corresponding optical density (COD) was calculated with immunohistochemical staining using NSE antibody. And the protective role of various groups on the cochlear SGC were compared. RESULTS: The positive staining rate of BDNF gene transfected BMSC with Nestin, NSE and GFAP antibody were all higher than that of BMSC in vitro (P < 0.01). After transplantation into cochleae, the differences of SGC density and COD among various groups were all significant on the same time points (P < 0.05). The SGC density and COD of the BDNF gene transfected BMSC group were the highest. The SGC density and COD of various groups on week 4 were all obviously decreased than those on week 1 and 2 (P < 0.05). CONCLUSION: AmAn-induced SGC damage could be depressed by BMSC, BDNF gene or BDNF gene transfected BMSC transplantation into cochleae, while BDNF gene transfected BMSC showed the best protective role.

[Expression of brain-derived neurotrophic factor modified bone marrow mesenchymal stem cells in the cochlea of drug deafened guinea pigs and its protection role].

OBJECTIVE: To study the expression of brain-derived neurotrophic factor (BDNF) gene modified bone marrow mesenchymal stem cells (MSC) in the cochlea of drug-deafened guinea pigs and its protection to spiral ganglion cells (SGC). METHODS: Guinea pigs deafened by subcutaneous injection of amikacin were randomly divided into two groups, BDNF gene modified bone marrow MSC were injected into the cochlea through fenestration of scala tympani in the experimental group, while artificial perilymphatic fluid were injected in the control group. Experimental animals were executed at 7 and 28 days post-operation. Expression of BDNF mRNA was examined by quantitate real time RT-PCR, histological images of cochlear sections were analyzed to calculate the cellular density of the SGC, and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was used to identify the apoptotic neurons. RESULTS: The BDNF expressive level in experimental group was higher than in the control group at 7 d and 28 d post-operation, whose differences were both statistically significant (P < 0.01). And, It showed a higher abundance of ganglion cell numbers, as well as a decreased apoptotic index in experimental group compared with the control group at 7 d and 28 d post-operation, whose differences were all statistically significant (P < 0.01). CONCLUSION: BDNF gene modified MSC could maintain expression for at least 28 days after transplantation into cochlea of drug deafened guinea pigs, and protect SGC.

[The incidence of facial nerve dehiscence at mastoidectomy and its risk factors].

OBJECTIVE: To study the incidence and locations of facial nerve dehiscence (FND) in mastoidectomy for the patients with cholesteatoma and chronic otitis media, and to determine its relevance as pre-operative prediction. METHOD: Three hundred and fifteen ears (217 ears with cholesteatoma and 98 with chronic otitis media) undergoing mastoidectomy with or without tympanoplasties were selected for retrospective study, in which the incidence and locations of FND was studied, and the relevance for FND were analyzed by univariate test following by multivariate stepwise logistic regression. RESULT: The presence of FND was 22.9% of total surgical procedures and the locations of FND were 93.1% in the tympanic segment, which was significantly higher than in the mastoid segment. The factors as otogenic facial paralysis, pathologic style (cholesteatoma or chronic otitis media) and lateral semicircular canal (LSC) fistula were related to FND, while others factors as sex, age, revision operations, preoperative complications, dural exposure, sigmoid sinus exposure were not risk factors for FND. CONCLUSION: The incidence of FND was 22.9% in this study, the most common location for FND was in the tympanic segment, therefore, the facial nerves should be especially taken care in mastoidectomy for patients with presence of otogenic facial paralysis, cholesteatoma and LSC fistula.