Global burden of head and neck cancers from 1990 to 2019.

Head and neck cancer (HNC) exerts a significant healthcare burden worldwide. Insufficient data impedes a comprehensive understanding of its global impact. Through analysis of the 2019 Global Burden of Disease (GBD) database, our secondary investigation unveiled a surging global incidence of HNC, yet a decline in associated mortality and disability-adjusted life years (DALYs) owing to enhanced prognosis. Particularly noteworthy is the higher incidence of escalation among females compared to males. Effective resource allocation, meticulous control of risk factors, and tailored interventions are imperative to curtail mortality rates among young individuals afflicted with HNC in underprivileged regions, as well as in elderly individuals grappling with thyroid cancer.

Emerging roles of circular RNAs in regulating the hallmarks of thyroid cancer.

Thyroid cancer is a prevalent endocrine malignancy with increasing incidence in recent years. Although most thyroid cancers grow slowly, they can become refractory, leading to a high mortality rate once they exhibit recurrence, metastasis, resistance to radioiodine therapy, or a lack of differentiation. However, the mechanisms underlying these malignant characteristics remain unclear. Circular RNAs, a type of closed-loop non-coding RNAs, play multiple roles in cancer. Several studies have demonstrated that circular RNAs significantly influence the development of thyroid cancers. In this review, we summarize the circular RNAs identified in thyroid cancers over the past decade according to the hallmarks of cancer. We found that eight of the 14 hallmarks of thyroid cancers are regulated by circular RNAs, whereas the other six have not been reported to be correlated with circular RNAs. This review is expected to help us better understand the roles of circular RNAs in thyroid cancers and accelerate research on the mechanisms and cure strategies for thyroid cancers.

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea.

Introduction: Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear. Methods: To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5). Results: A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids. Discussion: This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.

Store-Operated Ca2+ Channels Contribute to the Generation of Ca2+ Waves in Interdental Cells in the Cochleae.

Cochlear calcium (Ca2+) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca2+ waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca2+ waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca2+ wave formation and propagation by developing a single-cell Ca2+ excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca2+ excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca2+ channels in IDCs are responsible for Ca2+ wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca2+ waves. Our results provide the mechanism of Ca2+ formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca2+ waves in the cochlea, with good potential for research on cochlear Ca2+ and hearing functions.

A Flexible Thermocouple Film Sensor for Respiratory Monitoring.

A novel flexible thermocouple film sensor on a polyimide substrate is proposed that is simple and flexible for monitoring the respiratory signal. Several thermocouples were connected in series and patterned on the polyimide substrate, and each one is formed by copper and a constant line connected to each other at two nodes. The respiratory signal was measured by the output voltage, which resulted from the temperature difference between the hot and cold junctions. The sensors were fabricated with surface-microfabrication technology with three sputtering steps. The measurement results showed that the peak voltage decreased by 90% in the case of apnea compared with normal breathing. The sensor has potential application for wearable detection of sleep apnea hypopnea syndrome (OSAHS).

Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.

Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.

A reduced form of nicotinamide riboside protects the cochlea against aminoglycoside-induced ototoxicity by SIRT1 activation.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+), a coenzyme that plays crucial roles in many cellular processes, is a potential therapeutic target for various diseases. Dihydronicotinamide riboside (NRH), a novel reduced form of nicotinamide riboside, has emerged as a potent NAD+ precursor. Here, we studied the protective effects and underlying mechanism of NRH on aminoglycoside-induced ototoxicity. METHODS: Auditory function and hair-cell (HC) morphology were examined to assess the effects of NRH on kanamycin-induced hearing loss. The pharmacokinetic parameters of NRH were measured in plasma and the cochlea using liquid chromatography tandem mass spectrometry. NAD+ levels in organ explant cultures were assessed to compare NRH with known NAD+ precursors. Immunofluorescence analysis was performed to detect reactive oxygen species (ROS) and apoptosis. We analyzed SIRT1 and 14-3-3 protein expression. EX527 and resveratrol were used to investigate the role of SIRT1 in the protective effect of NRH against kanamycin-induced ototoxicity. RESULTS: NRH alleviated kanamycin-induced HC damage and attenuated hearing loss in mice. NRH reduced gentamicin-induced vestibular HC loss. Compared with NAD and NR, NRH produced more NAD+ in cochlear HCs and significantly ameliorated kanamycin-induced oxidative stress and apoptosis. NRH rescued the aminoglycoside-induced decreases in SIRT1 and 14-3-3 protein expression. Moreover, EX527 antagonized the protective effect of NRH on kanamycin-induced HC loss by inhibition of SIRT1, while resveratrol alleviated HC damage caused by EX527. CONCLUSIONS: NRH ameliorates aminoglycoside-induced ototoxicity by inhibiting HC apoptosis by activating SIRT1 and decreasing ROS. NRH is an effective therapeutic option for aminoglycoside-induced ototoxicity.

Oriented Growth of Neural Stem Cell-Derived Neurons Regulated by Magnetic Nanochains.

Neural stem cell therapy has become a promising cure in the treatment of neurodegenerative disorders. Owing to the anisotropy of the nervous system, the newly derived neurons need not only the functional integrity but also the oriented growth to contact with the partner cells to establish functional connections. So the oriented growth of the newly derived neurons is a key factor in neural stem cell-based nerve regeneration. Nowadays, various biomaterials have been applied to assist in the oriented growth of neural stem cell-derived neurons. However, among these biomaterials, the magnetic materials applied in guiding the neuronal growth are still fewer than the other materials, such as the fibers. So in this work, we developed the magnetic nanochains to guide the oriented growth of neural stem cell-derived neurons. With the guidance of the magnetic nanochains, the seeded neural stem cells exhibited a good arrangement, and the neural stem cell-derived neurons showed well-oriented growth with the orientation of the nanochains. We anticipated that the magnetic nanochains would have huge potential in stem cell-based nerve regeneration.

Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis.

Aminoglycoside antibiotics are widely used for the treatment of serious acute infections, life-threatening sepsis, and tuberculosis, but all aminoglycosides cause side effects, especially irreversible ototoxicity. The mechanisms underlying the ototoxicity of aminoglycosides need further investigation, and there are no effective drugs in the clinic. Here we showed that tetrandrine (TET), a bioactive bisbenzylisoquinoline alkaloid derived from Stephania tetrandra, ameliorated neomycin-induced cochlear hair cell injury. In both in vitro and in vivo experiments we found that TET administration significantly improved auditory function and reduced hair cell damage after neomycin exposure. In addition, we observed that TET could significantly decrease oxidative stress and apoptosis in hair cells after neomycin exposure. Finally, RNA-seq analysis suggested that TET protected against neomycin-induced ototoxicity mainly by promoting steroid biosynthesis. Collectively, our results provide pharmacological evidence showing that TET may be a promising agent in preventing aminoglycosides-induced ototoxicity.

Detecting epidemiological relevance of adenoid hypertrophy, rhinosinusitis, and allergic rhinitis through an Internet search.

PURPOSE: This study aimed to detect the epidemiological relevance between adenoid hypertrophy (AH) and rhinosinusitis, and AH and allergic rhinitis (AR) through an Internet search. METHODS: Internet search query data from January 2011 to December 2019 in China were retrieved from the Baidu Index (BI). Spearman's correlation coefficients were used to detect the correlation among the search volumes of AH, rhinosinusitis, and AR. We also collected search data from the first 5 months of 2020, when quarantine was implemented in China due to the coronavirus disease 2019 epidemic. Then, we compared the search data to those obtained during the same period in 2019 to assess the effects of isolation on AH and AR. RESULTS: Statistically significant relevance was found between the search variations of AH and rhinosinusitis during 2011-2019 (R = 0.643, P < 0.05). However, the relationship between AH and AR was weak (R = - 0.239, P < 0.05) and that between rhinosinusitis and AR (R = - 0.022, P > 0.05) was not relevant. The average monthly search volume of AH and rhinosinusitis had a strong correlation (R = 0.846, P < 0.01), but AH and AR and rhinosinusitis and AR were not correlated (R = - 0.350, P > 0.05; R = - 0.042, P > 0.05, respectively). AH and rhinosinusitis search volumes decreased consistently during the first 5 months of 2020 (isolation), whereas that for AR increased during January-February. CONCLUSION: AH had an epidemiological relationship with rhinosinusitis, which was not consistent with AR. The decrease in public gathering effectively reduced the morbidities of AH and rhinosinusitis but not those of AR.

The Impact of Glycolipid Metabolic Disorders on Severity Stage-Specific Variation of Cardiac Autonomic Function in Obstructive Sleep Apnea: A Data-Driven Clinical Study.

BACKGROUND: Cardiac autonomic dysfunction (CAD) is a common pathology in cardiovascular diseases; however, the role of glycolipid metabolic disorders in CAD development in obstructive sleep apnea (OSA) remains poorly understood. METHODS: In total, 4152 patients with suspected OSA were recruited in our sleep center. Metabolic characteristics including anthropometric and glycolipid data were collected. Heart rate variability (HRV) was measured to assess the risk of CAD; its dose-response relationship with OSA severity was evaluated via restricted cubic spline (RCS) analysis. A segmented multivariate linear regression (SMLR) model was used to evaluate the roles of metabolic variables in different stages of OSA. RESULTS: The RCS showed that CAD risk increased in a nonlinear relationship pattern with OSA severity, from slow fluctuation at earlier stages to rapid change in later stages. After integrating the clinical definition and RCS selected knots, we obtained the new four OSA severity stages. SMLR model showed that the overall value of glycolipid variables for prediction of HRV abnormalities was greater than the value of OSA variables at earlier stages, while OSA variables were more effective predictors in more severe stages. The discordance in respective relationship of HRV with metabolic and OSA variables sheds the light how metabolic disorders promoted the development of CAD in OSA, the later further in turn deteriorates cardiac function. CONCLUSION: These results are indicative of stage-specific involvement of glycolipid metabolic factors underlying CAD nonlinear changes in patients with OSA. Early control glycolipid disorders may help the control of CAD development in patients with OSA.

Influence of multiple apolipoprotein A-I and B genetic variations on insulin resistance and metabolic syndrome in obstructive sleep apnea.

BACKGROUND: The relationships between apolipoprotein A-I (APOA-I), apolipoprotein B (APOB) with insulin resistance, metabolic syndrome (MetS) are unclear in OSA. We aimed to evaluate whether the multiple single nucleotide polymorphism (SNP) variants of APOA-I and APOB exert a collaborative effect on insulin resistance and MetS in OSA. METHODS: Initially, 12 APOA-I SNPs and 30 APOB SNPs in 5259 subjects were examined. After strict screening, four APOA-I SNPs and five APOB SNPs in 4007 participants were included. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of APOA-I and APOB. Logistic regression analyses were used to evaluate the relationships between APOA-I/APOB genetic polymorphisms, insulin resistance, and MetS in OSA. RESULTS: Serum APOB levels increased the risk of insulin resistance and MetS adjusting for age, gender and BMI [odds ratio (OR = 3.168, P < 0.001; OR = 6.098, P < 0.001, respectively]. APOA-I GRS decreased the risk of insulin resistance and MetS after adjustments (OR = 0.917, P = 0.001; OR = 0.870, P < 0.001, respectively). APOB GRS had no association with insulin resistance (OR = 1.364, P = 0.610), and had weak association with MetS after adjustments (OR = 1.072, P = 0.042). In addition, individuals in the top quintile of the APOA-I genetic score distribution had a lower risk of insulin resistance and MetS after adjustments (OR = 0.761, P = 0.007; OR = 0.637, P < 0.001, respectively). CONCLUSIONS: In patients with OSA, cumulative effects of APOA-I genetic variations decreased the risk of insulin resistance and MetS, whereas multiple APOB genetic variations had no associations with insulin resistance and weak association with MetS.

Removal of biofilm is essential for long-term ventilation tube retention.

BACKGROUND: Although long-term retention of a ventilation tube is required in many ear diseases, spontaneous removal of conventional ventilation tube is observed in patients within 3 to 12 mo. To address this issue, we aimed to determine a new method for long-term retention of the ventilation tube. AIM: To explore the value of removing the biofilm for long-term retention of tympanostomy ventilation tubes. METHODS: A case-control study design was used to evaluate the safety and effectiveness of long-term tube retention by directly removing the biofilm (via surgical exfoliation) in patients who underwent myringotomy with ventilation tube placement. The patients were randomly divided into two groups: Control group and treatment group. Patients in the treatment group underwent regular biofilm exfoliation surgery in the clinic, whereas those in the control group did not have their biofilm removed. Only conventional ventilation tubes were placed in this study. Outcome measures were tube position and patency. Tube retention time and any complications were documented. RESULTS: Eight patients with biofilm removal and eight patients without biofilm removal as a control group were enrolled in the study. The tympanostomy tube retention time was significantly longer in the treatment group (43.5 ± 26.4 mo) than in the control group (9.5 ± 6.9 mo) (P = 0.003). More tympanostomy tubes were found to be patent and in correct position in the treatment group during the follow-up intervals than in the control group (P = 0.01). CONCLUSION: Despite the use of short-term ventilation tubes, direct biofilm removal can be a well-tolerated and effective treatment for long-term tube retention of tympanostomy ventilation tubes in patients who underwent myringotomy.

Surgical Treatment and Outcomes for Sinonasal and Skull Base Phosphaturic Mesenchymal Tumors.

OBJECTIVE: To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution. STUDY DESIGN: Retrospective case series. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019. RESULTS: There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia. CONCLUSIONS: A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.

Anxiety and depression in patients with nasal septal deviation.

OBJECTIVE: Nasal septal deviation (NSD) has a significant impact on patients' quality of life; however, there have been limited studies examining the psychological status of NSD patients. In this study, symptoms of depression and anxiety were investigated between NSD patients and controls using a self-report questionnaire. METHODS: A case-control study design was used to evaluate the psychological burden of NSD in patients who visited the general hospital. The control group comprised of ENT outpatients without a history of chronic nasal disease. The Zung Self-rating Anxiety/Depression Scale (SDS/SAS) was used to evaluate the prevalence and severity of anxiety and depression between the NSD and control group. RESULTS: Seventy-six patients with NSD and 79 control patients were enrolled in the study. We found that depression and anxiety, as well as the co-morbidity of depression with anxiety, were more common in the NSD group in comparison to the control (39.5% vs 22.8%, p = 0.025; 38.2% vs 15.2%, p = 0.001; and 27.6% vs 11.4%, p = 0.011, respectively). The average SDS and SAS score was higher in NSD patients compared to controls (SDS: 49.7 ± 13.1 vs 45.2 ± 10.4, p = 0.019 and SAS: 48.1 ± 11.6 vs 41.3 ± 9.3, p < 0.001, respectively), and NSD patients were found to have more severe levels of anxiety and depression. CONCLUSION: Depression and anxiety are more common and severe in patients with NSD. Therefore, psychological distress should be taken into consideration during the diagnostic and therapeutic process for patients with NSD.

Septal floor rotational flap pedicled on ethmoidal arteries for endoscopic skull base reconstruction.

OBJECT: Expanded endonasal approaches have dramatically changed how skull base surgery is performed, and nasoseptal flap (NSF) has significantly improved skull base reconstruction. However, challenges remain when the pterygopalatine artery is invaded by tumors; when it must be sacrificed to approach the lateral sphenoidal recess; when late-occurrence leak occurs in the sella after transsphenoidal surgery; and also when the leak is on the posterior wall of the frontal sinus, which is too distant for NSF to reach. This article describes a septal floor rotational flap pedicled on ethmoidal arteries for endoscopic skull base reconstruction in certain cases. STUDY DESIGN: Case series. METHOD: In this article, we retrospectively review a series of 19 patients who underwent skull base reconstruction with a septal floor rotational flap pedicled on the ethmoidal arteries. RESULT: All 19 flaps, including the anterior and posterior artery pedicled flaps, survived without significant complications, and no postoperative cerebrospinal fluid leak occurred during follow-up. CONCLUSION: Ethmoidal arteries pedicled septal floor rotational flap, with their strong blood supply and large coverage area, are ideal replacements for NSF. These flaps are qualified in locations ranging from the posterior wall of the frontal sinus to the lateral sphenoidal recess and in cases ranging from tumor invading the pterygopalatine fossa to sellar late-occurred leak after transsphenoidal surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2696-2701, 2019.

Fetal bovine serum inhibits neomycin-induced apoptosis of hair cell-like HEI-OC-1 cells by maintaining mitochondrial function.

Aging and exposure to noise or ototoxic drugs are major causes of hair cell death leading to human hearing loss, and many agents have been developed to protect hair cells from apoptosis. Fetal bovine serum (FBS) is a fundamental ingredient in the culture medium of hair cell-like House Ear Institute Organ of Corti 1 (HEI-OC-1) cells, but there have been no reports about the function of FBS in HEI-OC-1 cell apoptosis. In this study, we found that FBS deprivation alone significantly increased HEI-OC-1 cell apoptosis in the absence of neomycin exposure and that the presence of FBS significantly inhibited HEI-OC-1 cell apoptosis after neomycin exposure compared to FBS-deprived cells. Further, we found that the protective effect of FBS was dose dependent and more effective than the growth factors B27, N2, EGF, bFGF, IGF-1, and heparan sulfate. We also found that FBS deprivation significantly disrupted the expression level of mitochondrial proteins, increased pro-apoptotic gene expression, decreased the mitochondrial membrane potential, and increased reactive oxygen species accumulation in HEI-OC-1 cells after neomycin exposure. These findings indicate that FBS is involved in maintaining the level of mitochondrial proteins, maintaining the balance of oxidant gene expression, and preventing the accumulation of ROS, and thus FBS maintains normal mitochondrial function and inhibits apoptosis in HEI-OC-1 cells after neomycin exposure.

Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function.

Inherited hearing loss is associated with gene mutations that result in sensory hair cell (HC) malfunction. HC structure is defined by the cytoskeleton, which is mainly composed of actin filaments and actin-binding partners. LIM motif-containing protein kinases (LIMKs) are the primary regulators of actin dynamics and consist of two members: LIMK1 and LIMK2. Actin arrangement is directly involved in the regulation of cytoskeletal structure and the maturation of synapses in the central nervous system, and LIMKs are involved in structural plasticity by controlling the activation of the actin depolymerization protein cofilin in the olfactory system and in the hippocampus. However, the expression pattern and the role of LIMKs in mouse cochlear development and synapse function also need to be further studied. We show here that the Limk genes are expressed in the mouse cochlea. We examined the morphology and the afferent synapse densities of HCs and measured the auditory function in Limk1 and Limk2 double knockout (DKO) mice. We found that the loss of Limk1 and Limk2 did not appear to affect the overall development of the cochlea, including the number of HCs and the structure of hair bundles. There were no significant differences in auditory thresholds between DKO mice and wild-type littermates. However, the expression of p-cofilin in the DKO mice was significantly decreased. Additionally, no significant differences were found in the number or distribution of ribbon synapses between the DKO and wild-type mice. In summary, our data suggest that the Limk genes play a different role in the development of the cochlea compared to their role in the central nervous system.

Delayed Diagnosis and Treatment of Cerebrospinal Fluid Leakage in Current Practice.

As delayed diagnosis and treatment of cerebrospinal fluid (CSF) leakage are common in current practice, this study was performed to determine associated factors and discuss appropriate strategies to deal with these problems. A retrospective analysis of all cases of CSF leakage in our hospital from 2007 to 2018, including 41 patients with CSF rhinorrhea and 5 with CSF otorhinorrhea, was performed. Symptoms, associated diseases, misdiagnoses, history of skull base repair surgical, previous medical costs, and number of hospital visits before visiting our institution were reviewed. The diagnoses, surgical reconstruction methods, and prognoses of the patients were analyzed. In 18 patients, CSF leakage was spontaneous, in 14 the cause was trauma, and in the remaining 14 the origin was iatrogenic. Twelve patients had been misdiagnosed with allergic rhinitis, rhinosinusitis, or otitis media. Twelve cases had intracranial infection and 14 suffered airway infection. Six had undergone unsuccessful craniotomy, endonasal endoscopic surgery, or ear surgery for treatment of CSF leakage before visiting our institute. This resulted in an average of 5.13 ±â€Š1.32 referrals and medical costs of up to 20,795.7 ±â€Š4553.80 RMB. The success rate was 97.83% after repairing CSF fistulae in our hospital. The septal floor flap (SFF) method (based on ethmoidal arteries) to treat CSF rhinorrhea showed a success rate of 100% in 12 patients. Therefore, early localization, clinical diagnosis, and appropriate repair surgery can avoid the occurrence of delayed events. Pedicled flaps, including SFF, are recommended to manage challenging CSF rhinorrhea.

The Key Transcription Factor Expression in the Developing Vestibular and Auditory Sensory Organs: A Comprehensive Comparison of Spatial and Temporal Patterns.

Inner ear formation requires that a series of cell fate decisions and morphogenetic events occur in a precise temporal and spatial pattern. Previous studies have shown that transcription factors, including Pax2, Sox2, and Prox1, play important roles during the inner ear development. However, the temporospatial expression patterns among these transcription factors are poorly understood. In the current study, we present a comprehensive description of the temporal and spatial expression profiles of Pax2, Sox2, and Prox1 during auditory and vestibular sensory organ development in mice. Using immunohistochemical analyses, we show that Sox2 and Pax2 are both expressed in the prosensory cells (the developing hair cells), but Sox2 is later restricted to only the supporting cells of the organ of Corti. In the vestibular sensory organ, however, the Pax2 expression is localized in hair cells at postnatal day 7, while Sox2 is still expressed in both the hair cells and supporting cells at that time. Prox1 was transiently expressed in the presumptive hair cells and developing supporting cells, and lower Prox1 expression was observed in the vestibular sensory organ compared to the organ of Corti. The different expression patterns of these transcription factors in the developing auditory and vestibular sensory organs suggest that they play different roles in the development of the sensory epithelia and might help to shape the respective sensory structures.