Analysis of mRNA m6A modification and mRNA expression profiles in middle ear cholesteatoma.

Introduction: Middle ear cholesteatoma is characterized by the hyperproliferation of keratinocytes. In recent decades, N6-methyladenosine (m6A) modification has been shown to play an essential role in the pathogenesis of many proliferative diseases. However, neither the m6A modification profile nor its potential role in the pathogenesis of middle ear cholesteatoma has currently been investigated. Therefore, this study aimed to explore m6A modification patterns in middle ear cholesteatoma. Materials and methods: An m6A mRNA epitranscriptomic microarray analysis was performed to analyze m6A modification patterns in middle ear cholesteatoma tissue (n = 5) and normal post-auricular skin samples (n = 5). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the potential biological functions and signaling pathways underlying the pathogenesis of middle ear cholesteatoma. Subsequently, m6A modification levels were verified by methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) in middle ear cholesteatoma tissue and normal skin samples, respectively. Results: A total of 6,865 distinctive m6A-modified mRNAs were identified, including 4,620 hypermethylated and 2,245 hypomethylated mRNAs, as well as 9,162 differentially expressed mRNAs, including 4,891 upregulated and 4,271 downregulated mRNAs, in the middle ear cholesteatoma group relative to the normal skin group. An association analysis between methylation and gene expression demonstrated that expression of 1,926 hypermethylated mRNAs was upregulated, while expression of 2,187 hypomethylated mRNAs and 38 hypermethylated mRNAs was downregulated. Moreover, GO analysis suggested that differentially methylated mRNAs might influence cellular processes and biological behaviors, such as cell differentiation, biosynthetic processes, regulation of molecular functions, and keratinization. KEGG pathway analysis demonstrated that the hypermethylated transcripts were involved in 26 pathways, including the Hippo signaling pathway, the p53 signaling pathway, and the inflammatory mediator regulation of transient receptor potential (TRP) channels, while the hypomethylated transcripts were involved in 13 pathways, including bacterial invasion of epithelial cells, steroid biosynthesis, and the Hippo signaling pathway. Conclusion: Our study presents m6A modification patterns in middle ear cholesteatoma, which may exert regulatory roles in middle ear cholesteatoma. The present study provides directions for mRNA m6A modification-based research on the epigenetic etiology and pathogenesis of middle ear cholesteatoma.

Efficacy of endoscopic porcine small intestinal submucosa graft myringoplasty: a retrospective comparative study.

BACKGROUND: The surgical outcomes following tympanic membrane (TM) repair are affected by many factors. OBJECTIVES: To evaluate the efficacy of endoscopic porcine small intestine submucosa graft (PSISG) myringoplasty by comparing with endoscopic myringoplasty with temporal fascia (TF) and perichondrium (PC). METHODS: We conducted a retrospective comparative study that a total of 98 patients with TM perforations were included. The patients underwent endoscopic myringoplasty using PSISG, TF or PC as the graft. The closure rate, hearing outcomes, operative time and complications in three groups were compared. RESULTS: At 3 months postoperatively, the closure rate were 85.2% (23/27), 92.1% (35/38) and 87.9% (29/33) in the PSISG, TF and PC groups respectively (p = .667); Hearing improved after surgery in three groups (p < .001), and showed no significant difference among the three groups. The mean operative time of the PSISG group was shorter than autologous TF (p < .001) and PC groups (p < .001) in this study; No operative or postoperative complications were found among the three groups. CONCLUSION: Compare to autologous temporal fascia or perichondrium, the PSISG appears to be an effective and safe material for TM perforations closure. Endoscopic PSISG myringoplasty may be an alternative technique for repairing TM perforations, especially for revision cases.

Microarray analysis and functional prediction of differentially expressed circular RNAs in acquired middle ear cholesteatoma.

BACKGROUND: Middle ear cholesteatoma is characterized by hyper-proliferation of keratinocytes. Circular RNA (circRNA) plays an essential role in the pathogenesis of many proliferative diseases. However, the role of circRNA in the etiopathogenesis of middle ear cholesteatoma is rarely investigated so far. We aimed to investigate the differential expression profiling of circRNAs between acquired middle ear cholesteatoma and normal skin, and to identify potential circRNAs contributing to the etiopathogenesis of middle ear cholesteatoma. Microarray analysis and functional prediction were performed to investigate the circRNA expression profiling between middle ear cholesteatoma and normal skin. Validation of differentially expressed circRNAs was conducted by qRT-PCR. Prediction of m6A modification was also carried out. RESULTS: Microarray analysis displayed that totally 93 up-regulated and 85 down-regulated circRNAs were identified in middle ear cholesteatoma. Through validation, expressions of hsa_circRNA_104327 and hsa_circRNA_404655 were significantly higher, while hsa_circRNA_000319 was significantly down-regulated in cholesteatoma. GO classification, KEGG pathway, and ceRNA network analyses suggested that these differentially expressed circRNAs might play important roles in the etiopathogenesis of middle ear cholesteatoma. Prediction of m6A modification exhibited that hsa_circRNA_000319 possessed 4 m6A sites with very high confidence, and hsa_circRNA_404655 had 3 m6A sites with high confidence. CONCLUSIONS: Our study revealed that these differentially expressed circRNAs might contribute to the etiopathogenesis of middle ear cholesteatoma. Further researches should be conducted to investigate the exact mechanism of these differentially expressed circRNAs in the etiopathogenesis of middle ear cholesteatoma. Targeting on these circRNAs may provide a new strategy for middle ear cholesteatoma therapy in the future.

Effectiveness of salvage intratympanic dexamethasone treatment for refractory sudden sensorineural hearing loss classified by audiogram patterns.

BACKGROUND: Intratympanic dexamethasone is commonly conducted to treat refractory sudden sensorineural hearing loss (RSSNHL). However, no consensus has been reached on its effectiveness. OBJECTIVES: The study aimed to evaluate the effectiveness of otoendoscope-assisted salvage intratympanic dexamethasone treatment (IDT) on RSSNHL with different audiogram patterns after failure of initial therapy. MATERIAL AND METHODS: A total of 108 patients with unilateral RSSNHL were classified into 4 groups according to audiogram patterns. Hearing results were evaluated by pure-tone audiometry (PTA), which was performed at baseline and one month after otoendoscope-assisted salvage IDT. The effectiveness of otoendoscope-assisted salvage IDT was assessed in each group. RESULTS: The efficiency in low-frequency, high-frequency, flat, and deaf group was 48%, 24.1%, 46.2%, 17.9%, respectively. The efficacy did not differ between the high-frequency and deaf group. Notably, the efficacy in the low-frequency and flat group was significantly higher than that in the deaf group. CONCLUSIONS: Otoendoscope-assisted salvage IDT is a safe and effective treatment for RSSNHL. This treatment provided better results for patients with low-frequency damaged and flat curve audiogram than patients with other audiogram patterns. SIGNIFICANCE: Audiogram patterns should be considered in the clinical management of patients with RSSHNL prior to salvage IDT.

Nuclear factor E2 related factor (NRF2) inhibits mast cell- mediated allergic inflammation via SIRT4-mediated mitochondrial metabolism.

BACKGROUND: Mast cell (MC)-mediated inflammation is essential for allergic rhinitis, and nuclear factor E2 related factor (NRF2) is found to inhibit inflammation. This study investigated whether NRF2 could inhibit MC inflammation and its molecular mechanisms concerning SIRT4. METHODS: Real-time quantitative PCR (RT-qPCR) and western blot were used to detect gene expression, and Elisa kit was used to detect the content of histamine and inflammatory cytokines in the medium of MCs, and Seahorse XF instrument was used to measure the mitochondrial metabolism of MCs. Knockdown SIRT4 and establish SIRT4 overexpression of HMC-1 cells to study the function of SIRT4. RESULTS: As an activator of NRF2, 4-Octyl Itaconate increases not only NRF2 expression but also increases SIRT4 expression. Although 4-Octyl Itaconate could reduce the histamine release and degranulation of MCs, which was induced by compound 48/80, SIRT4 knockdown decreased the inhibition of 4-Octyl Itaconate. Similarly,4-Octyl Itaconate inhibited the secretion of inflammatory cytokines (TNF-α, IL-1ß, IL6, and IL-8) by MCs, which was induced by LPS, but SIRT4 knockdown decreases the inhibition of 4-Octyl Itaconate. Also, the up-regulation of SIRT4 significantly inhibited mitochondrial metabolism in MCs and inhibited SIRT1 and P-p65 protein expression after inducing by 100 ng/mL LPS for 1 hour. CONCLUSIONS: NRF2 inhibits MC degranulation and MC-mediated inflammation by promoting SIRT4, and SIRT4 overexpression inhibits the mitochondrial metabolism of MCs.

Expression of PTHrP and RANKL in acquired middle ear cholesteatoma epithelium.

Background: Regarded as the most important clinical characteristic of middle ear cholesteatoma, the exact mechanism of bone resorption in cholesteatoma still remains unknown.Objectives: To investigate protein expression of PTHrP and RANKL in acquired middle ear cholesteatoma epithelium and analyze their functional roles in the etiopathogenesis of bone resorption in middle ear cholesteatoma.Material and methods: A total of 22 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. Protein expression of PTHrP and RANKL in middle ear cholesteatoma and normal postauricular skin was investigated by immunohistochemical staining. Correlations between bone resorption degree and expression of PTHrP and RANKL were also analyzed.Results: Protein expression of PTHrP and RANKL in cholesteatoma epithelium significantly increased when compared with normal postauricular skin epithelium. In cholesteatoma epithelium, a significantly positive association was observed between PTHrP and RANKL expression. Meanwhile, obviously positive correlations between protein expression of PTHrP and RANKL and bone resorption degree were discovered.Conclusions and significance: The increased protein expression of PTHrP and RANKL in cholesteatoma epithelium, and their associations with the degree of bone resorption, revealing that PTHrP might promote bone resorption process in middle ear cholesteatoma through RANKL signaling pathway.

Circle RNA hsa_circRNA_100290 serves as a ceRNA for miR-378a to regulate oral squamous cell carcinoma cells growth via Glucose transporter-1 (GLUT1) and glycolysis.

Aerobic glycolysis (the Warburg effect) is a robust metabolic hallmark of most tumors, including oral squamous cell carcinoma (OSCC). Glucose transporter 1 (GLUT1), a major glucose transporter regulating the glucose uptake, is upregulated in OSCC and participated in the cell glycolysis of OSCC. The deregulation and function of noncoding RNAs in cancers have been widely reported. Reportedly, hsa_circular RNA (circRNA)_100290 (circ_SLC30A7) is significantly upregulated (fold change = 6.91, p < 0.0000001) in OSCC. According to online tools prediction (miRWalk, miRanda, and Targetscan), miR-378a could simultaneously target circRNA_100290 and GLUT1. Herein, the expression of circRNA_100290 and GLUT1 remarkably increased in oral tumor tissue specimens and cells. In OSCC cell lines, cell proliferation and glycolysis could be remarkably downregulated by circRNA_100290 silence, which could be rescued by GLUT1 overexpression. Conversely, miR-378a expression could be remarkably inhibited in tumor tissue specimens and cells. The effect of miR-378a overexpression on OSCC cells was similar to those of circRNA_100290 silence. miR-378a directly bound to circRNA_100290 and GLUT1 3'-untranslated region, circRNA_100290 could remarkably relieve miR-378a-induced inhibition on GLUT1 via acting as a competing endogenous RNA (ceRNA). miR-378a inhibition remarkably attenuated the effect of circRNA_100290 silence on cell proliferation and glycolysis in OSCC cell lines. In summary, circRNA_100290 serves as a ceRNA to counteract miR-378a-mediated GLUT1 suppression, thus promoting glycolysis and cell proliferation in OSCC. We provide a reliable experimental basis for understanding the mechanism of cell growth and glycolysis deregulation in OSCC.

Microarray Analysis of Differentially-expressed MicroRNAs in Acquired Middle Ear Cholesteatoma.

Objectives: To analyze the miRNAs expression profiling between acquired middle ear cholesteatoma and normal skin, and to identify several novel miRNAs which may be involved in the etiopathogenesis of middle ear cholesteatoma. Methods: MiRNA microarray technology was adopted to analyze the miRNA expression profiling between acquired middle ear cholesteatoma and normal skin. qRT-PCR was used to validate selected differentially expressed miRNAs. Results: The miRNA microarray technology showed totally 44 upregulated (miRNA-21-3p, miRNA-584-5p, miRNA-16-1-3p, etc) and 175 downregulated (miRNA-10a-5p, miRNA-152-5p, miRNA-203b-5p, etc) miRNAs in cholesteatoma tissues with 2-fold change compared with normal skin. The qRT-PCR validation was in accordance with the microarray results partly: miRNA-21-3p and miRNA-16-1-3p expressed significantly higher while miRNA-10a-5p exhibited an obviously decreased expression in middle ear cholesteatoma tissues when compared with normal skin. The GO and KEGG pathway analyses provided clues that these differentially expressed miRNAs might play essential roles in the etiopathogenesis of middle ear cholesteatoma, including cell proliferation, apoptosis, cell cycle, differentiation, bone resorption and remodeling process. Conclusions: Our study suggests possible roles of differentially expressed miRNAs in the pathogenesis of middle ear cholesteatoma. Targeting on these miRNAs may provide a new strategy for cholesteatoma therapy in the future.

Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against Acoustic Trauma.

Noise is the most common occupational and environmental hazard, and noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit. Although therapeutics that target the free-radical pathway have shown promise, none of these compounds is currently approved against NIHL by the United States Food and Drug Administration. The present study has demonstrated that tetrandrine (TET), a traditional Chinese medicinal alkaloid and the main chemical isolate of the Stephania tetrandra S. Moore herb, significantly attenuated NIHL in CBA/CaJ mice. TET is known to exert antihypertensive and antiarrhythmic effects through the blocking of calcium channels. Whole-cell patch-clamp recording from adult spiral ganglion neurons showed that TET blocked the transient Ca2+ current in a dose-dependent manner and the half-blocking concentration was 0.6 + 0.1 µM. Consistent with previous findings that modulations of calcium-based signaling pathways have both prophylactic and therapeutic effects against neural trauma, NIHL was significantly diminished by TET administration. Importantly, TET has a long-lasting protective effect after noise exposure (48 weeks) in comparison to 2 weeks after noise exposure. The otoprotective effects of TET were achieved mainly by preventing outer hair cell damage and synapse loss between inner hair cells and spiral ganglion neurons. Thus, our data indicate that TET has great potential in the prevention and treatment of NIHL.

HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma.

CONCLUSIONS: The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma. OBJECTIVE: To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation. METHODS: A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed. RESULTS: On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

The role of bone resorption in the etiopathogenesis of acquired middle ear cholesteatoma.

Cholesteatoma is a destructive squamous epithelial lesion of the temporal bone which gradually expands and leads to serious complications by destruction of nearby bony structures. Erosion caused by bone resorption of the ossicular chain and bony labyrinth may result in hearing loss, vestibular dysfunction, facial paralysis, labyrinthine fistulae and intracranial complications. The exact underlying cellular and molecular mechanism of bone resorption in acquired cholesteatoma still remains unexplained. Pubmed database and China National Knowledge Infrastructure were screened for articles focusing on bone resorption in acquired cholesteatoma. Osteoclast activation, pressure necrosis, acid lysis, enzyme mediation, inflammatory mediators and several newly discovered biomolecules are outlined as main theories behind bone resorption in acquired cholesteatoma, aiming to facilitate the development of potential therapeutic targets for preventing intracranial and extracranial complications caused by bone resorption in acquired middle ear cholesteatoma.

DAPT mediates atoh1 expression to induce hair cell-like cells.

Hearing loss is currently an incurable degenerative disease characterized by a paucity of hair cells (HCs), which cannot be spontaneously replaced in mammals. Recent technological advancements in gene therapy and local drug delivery have shed new light for hearing loss. Atoh1, also known as Math1, Hath1, and Cath1, is a proneural basic helix-loop-helix (bHLH) transcription factor that is essential for HC differentiation. At various stages in development, Atoh1 activity is sufficient to drive HC differentiation in the cochlea. Thus, Atoh1 related gene therapy is the most promising option for HC induction. DAPT, an inhibitor of Notch signaling, enhances the expression of Atoh1 indirectly, which in turn promotes the induction of a HC fate. Here, we show that DAPT cooperates with Atoh1 to synergistically promote HC fate in ependymal cells in vitro and promote hair cell regeneration in the cultured basilar membrane (BM) which mimics the microenvironment in vivo. Taken together, our findings demonstrated that DAPT is sufficient to induce HC-like cells via enhancing of the expression of Atoh1 to inhibit the progression of HC apoptosis and to induce new HC formation.

Acquired cholesteatoma epithelial hyperproliferation: Roles of cell proliferation signal pathways.

OBJECTIVES/HYPOTHESIS: To review the recent cell proliferation signal pathways in the etiopathogenesis of acquired middle ear cholesteatoma. DATA SOURCES: PubMed (to September 2015). REVIEW METHODS: Articles about cell proliferation signal pathways in the etiopathogenesis of acquired cholesteatoma and treatment advances were searched in the PubMed database, from which 73 were included in this review. RESULTS: The exact underlying cellular and molecular mechanism of acquired cholesteatoma still remains unknown. Recent research tends to regard the proliferation of cholesteatoma epithelial cells as the mechanism of cholesteatoma pathogenesis. Cell proliferation signal pathways including epidermal growth factor receptor/phosphoinositide 3-kinase/protein kinase B signal pathway, mitogen-activated protein kinase signal pathway, interleukin-6/signal transducer and activator of transcription 3 signal pathway, inhibitor of DNA binding/differentiation-1/nuclear factor-κB/cyclinD1 signal pathway, microRNA-mediated proliferation signal pathway, and keratinocyte growth factor/keratinocyte growth factor receptor signal pathway have been proven to play important roles in acquired middle ear cholesteatoma. CONCLUSIONS: This review outlines the main biological properties of certain cell proliferation signal pathways, aiming to facilitate the development of potential therapeutic targets for intratympanic drug therapy for the nonsurgical or complementary treatment of cholesteatoma. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1923-1930, 2016.

[Clinical multi-center study on the treatment of sudden sensorineural hearing loss accompanied with feeling of ear fullness].

OBJECTIVE: To investigate the therapeutic effect of drug treatment for patients with sudden sensorineural hearing loss (SSNHL) accompanied with feeling of ear fullness (FEF). METHODS: A prospective clinical multicenter research was carried out from August 2007 to October 2011. SSNHL patients aged between 18 to 65 years old and accepted no medication were recruited, with a duration less than two weeks. The patients were divided into four types according to the hearing curve: type A was acute SSNHL in low tone frequencies, type B was acute SSNHL in high tone frequencies, type C was acute SSNHL in all frequencies, and type D was total deafness. Each type was subdivided into two groups by the accompaniment of SEF or not. And each type had four different treatment programs, based on the unified designed randomized table. All patients were followed up for four weeks from the initial examination. RESULTS: A total of 1 024 cases with single side SSNHL were recruited in the study from 33 hospitals in China, including 565 cases accompanied with FEF (55.18%), and 459 cases without FEF (44.82%). By classification of audiogram, 205 cases were type A (20.20%), of whom 122 were accompanied with FEF (59.51%); 141 cases belonged to type B (13.77%), of whom 74 were accompanied with FEF (52.48%); 402 cases were type C (39.25%), of whom 229 were accompanied with FEF (56.97%); and 276 cases were classified as type D (26.95%), of whom 140 were accompanied with FEF (50.72%). No significant difference was observed in total effective rate between the SSNHL patients accompanied with FEF or not in four acoustic types (P > 0.05). Among four acoustic types, the clinical cure rate of patients accompanied with FEF in type A was 93.44%, ranking the first; followed by 84.28% for type C; 75.71% for type D; and 70.27% for type B, respectively. CONCLUSIONS: The therapeutic effect for patients accompanied with FEF in type A is satisfactory. The presence of FEF do not impact the therapeutic effect for SSNHL patients.

Intratympanic dexamethasone injections for refractory Meniere' s disease.

Intratympanic injections or titration is a potential medical therapeutic strategy for patients with incurable inner ear diseases. Dexamethasone represent an attractive steroid source in intratympanic steroids strategies in the treatment of inner ear disorders. Here, we evaluated the effectiveness of intratympanic dexamethasone injections (IDI) in outpatients with refractory Meniere's disease (MD). Vestibular function measured by Vestibular Ocular Reflex (VOR) gain and caloric test revealed that 21 outpatients out of 43 (48.8%) had complete sufficient vertigo control, while 9 (20.9%) of them were attached to fundamental manipulation. Out of the 13 remaining outpatients, 4 (9.3%) had a limit control and 9 had less modification. Therefore, 5 of 9 received re-treatment with IDI and 2 of 9 patients were administered ablative treatment with gentamicin. Meanwhile, audiology data suggested that 3 (7.0%), 4 (9.3%), 32 (74.4%), 4 (9.3%) patients were attached to the level of A, B, C, D, respectively. Furthermore, the symptom of tinnitus in 5 outpatients vanished, 21 (48.8%) diminished, 10 (23.3%) invariable, 7 (16.3%) aggravated. In 4 of 24 cases (16.7%), aural fullness disappeared after IDI, when the aural fullness was alleviated in 11 cases (45.8%) even intensive in 9 patients (37.5%). Together, our results demonstrate that intratympanic dexamethasone injection, as an effective therapeutic strategy for refractory Meniere's disease, could either be used for cascade therapy preoperation or used for patients who couldn't accept the surgery.

[Langerhans cell histiocytosis of the temporal bone in children: 7 cases analysis].

OBJECTIVE: To analyze the clinical manifestations, diagnosis, therapy and prognosis of Langerhans cell histiocytosis (LCH) of the temporal bone in children. METHOD: Seven children with LCH of the temporal bone n our hospital were retrospectively summed up from April 2009 to April 2014. The patients were followed up 1-5 years, their clinical manifestations, imaging findings, diagnosis, therapy and prognosis were studied. Correlation between clinical classifications and prognosis was also analyzed. RESULT: Among the 7 patients, 4 were boys and 3 were girls. 5 cases belonged to the single system group and 2 cases belonged to the multisystem group. The most common clinical characters were temporal tumor, otorrhea, otalgia, hearing loss and granulation of external auditory canal. CT of the temporal bones showed extensive osteolytic destructions with diffuse soft tissure density, without border sclerotization. The cases were. received different therapies. Followed up for 1-5 years, 4 cases were regressive, 1 case kept stable, while 2 cases showed progressive. The two boys then received standard treatment combined steroids with vinblastine. The prognosis in the multisystem group was significantly different from the single system group (P < 0.05). CONCLUSION: The clinical manifestations of LCH vary a lot. The diagnosis is based on histological and immunophenotypic examination of lesion tissue. The main therapy includs surgery, chemotherapy and radiotherapy. The prognosis of the single system group is much better than the multisystem group.

Primary thyroid diffuse large B-cell lymphoma coexistent with papillary thyroid carcinoma: A case report.

BACKGROUND: Primary thyroid lymphoma (PTL) is uncommon, accounting for 2% to 5% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) is the most frequent thyroid cancer. The coexistence of PTL and PTC is very rare, and the preoperative diagnosis is rather difficult. METHODS: A 41-year-old male patient complaining of fast painless thyroid enlargement for 2 months and a cervical mass for half a month was presented. Imaging demonstrated an enlarged thyroid and a mass in the thyroid. RESULTS: Surgery was conducted, and the final diagnosis of coexistence of PTL and PTC was confirmed by histopathological and immunohistochemical examination. The patient was then treated with cyclophosphamide, hydroxy doxorubicin, oncovin, prednisone (CHOP) chemotherapy and radiotherapy. After 2 months of follow-up, no recurrence or metastasis was noted. CONCLUSION: This rare case highlights the importance for physicians to keep PTL in mind for differential diagnosis in patients with sudden thyroid enlargement and who have clinical history of Hashimoto thyroiditis.

Activation of the IL-6/JAK/STAT3 signaling pathway in human middle ear cholesteatoma epithelium.

Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma.

[Intratympanic therapy in the management of tinnitus].

Tinnitus is a common symptom which often becomes disabling, affecting the emotional and psychosocial dimensions of life. Nowadays, therapies for tinnitus vary greatly, none of which could give a satisfactory therapeutic effect however. Intratympanic therapy allows the generation of high concentration of drugs within the inner ear without systemic side effects. This review aims to introduce the commonly used medications and approaches for intratympanic management of tinnitus. Although different medications have been tested for their effects on tinnitus by intratympanic application, no breakthrough has been achieved so far. Consequently, the clinical use of specific medications for tinnitus has remained limited. A more widespread adoption of intratympanic management requires the development of specific medications for tinnitus, as well as proof of their safety and efficacy.