Lipopolysaccharide induces autophagy by targeting the AMPK-mTOR pathway in Human Nasal Epithelial Cells.

Chronic rhinosinusitis (CRS) is a well-known disease encountered in the department of otorhinolaryngology, yet little is known about its pathogenesis. Autophagy, a lysosome-dependent degradation process, has been reported to be involved in the process of many chronic inflammatory diseases. Here we tried to evaluate the function of autophagy in CRS as well as explore the related mechanisms. We first stained light chain 3B (LC3B) with immunohistochemistry in uncinate tissues (UT) from patients with and without CRS and found that its expression was up-regulated in CRS patients. Then, Human Nasal Epithelial Cells (HNEpC) were treated with lipopolysaccharide (LPS), one of the most common pathogenic elements in CRS, and we found that autophagy was induced in a dose- and time-dependent manner. This is supported by a rise in the expression of light chain 3B-II (LC3B-II), accumulation of GFP-LC3 vesicles, as well as decreased p62 expression. Furthermore, we found that LPS promoted AMPK phosphorylation and inactived mTOR, while AMPK inhibition by compound C significantly attenuated LPS-induced autophagy. Besides, treatment of HNEpC with LPS increased the amount of Toll-like receptor 4 (TLR4) while inhibiting TLR4 by Polymyxin B (PMB) declined autophagy caused by LPS. Taken together, our study first demonstrated that LPS caused autophagy in HNEpC, and this process was AMPK-mTOR dependent. These data suggested the relationship between LPS and autophagy in the pathogenesis of CRS.

Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway.

Astaxanthin is an oxygen-containing derivative of carotenoids that effectively suppresses reactive oxygen and has nutritional and medicinal value. The mechanisms underlying the effects of astaxanthin on isoflurane­induced neuroapoptosis remain to be fully understood. The present study was conducted to evaluate the protective effect of astaxanthin to reduce isoflurane­induced neuroapoptosis and to investigate the underlying mechanisms. The results demonstrated that isoflurane induced brain damage, increased caspase­3 activity and suppressed the phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) signaling pathway in an in vivo model. However, treatment with astaxanthin significantly inhibited brain damage, suppressed caspase­3 activity and upregulated the PI3K/Akt pathway in the isoflurane­induced rats. Furthermore, isoflurane suppressed cell growth, induced cell apoptosis, enhanced caspase­3 activity and downregulated the PI3K/Akt pathway in organotypic hippocampal slice culture. Administration of astaxanthin significantly promoted cell growth, reduced cell apoptosis and caspase­3 activity, and upregulated the PI3K/Akt pathway and isoflurane­induced neuroapoptosis. The present study demonstrated that downregulation of the PI3K/Akt pathway reduced the effect of astaxanthin to protect against isoflurane­induced neuroapoptosis in the in vitro model. The results of the current study suggested that the protective effect of astaxanthin reduces the isoflurane-induced neuroapoptosis via activation of the PI3K/Akt signaling pathway.

[Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea].

OBJECTIVE: To present the surgical technique and clinical effect of transnasal endoscopic repair of cerebrospinal fluid (CSF) rhinorrhea. METHODS: From 1996 to 2010, 54 patients with CSF rhinorrhea were treated with intranasal endoscopic surgery, including 25 patients with traumatic CSF rhinorrhea, 17 patients with spontaneous CSF rhinorrhea, and 12 patients with iatrogenic CSF rhinorrhea. The temporalis muscle, temporalis fascial, middle turbinate mucosa, nasal septum mucosa, inferior turbinate mucosa, fascia lata, leg muscle, abdominal fat, uncinate process mucosa and sinus mucosa were used to repair the fistulae. RESULTS: Forty-nine patients were successfully treated after the first operation, 1 after the second attempt, 1 after the third attempt, and 1 was successfully treated at the second operation in other hospital, 1 stopped therapy after an unsuccessful repairing. One patient recurred within one and a half years after operation and stopped therapy. Seven patients developed complications after the operation (high fever in 4, high fever and transient mild coma in 1, epilepsy in 1, pneumocephalus in 1) and were cured afterwards. CONCLUSIONS: Transnasal endoscopic surgery is safe, effective and microinvasive treatment for patients with CSF rhinorrhea, it is the first choice for repairing of CSF rhinorrhea for its high successful rate. Accurate leakage site identification, selection of suitable approach and repairing method are critical to the success of operation.

Anesthesiologist's knowledge and attitudes about obstructive sleep apnea: a survey study.

OBJECTIVE: The objectives of this study were to measure the anesthesiologists' knowledge and attitudes about OSA and assess the need for additional educational programs focusing on OSA. METHODS: The Obstructive Sleep Apnea Knowledge and Attitude Questionnaire (OSAKA) developed by Helena Metal was translated into Chinese and distributed to anesthesiologists from Shandong Province. Anesthesiologists completed the OSAKA questionnaire containing sections regarding knowledge (18 items) and attitudes about OSA (5 items). RESULTS: A total of 321 questionnaires were completed. The mean total knowledge score was 11.21, with the scores ranging from 2 to 17. The total correct score ratio was 62%. The knowledge score positively corrected with the participants' job titles and attitude scores. None of the dependent variables, such as sex, age, education, and working in a different hospital level, affected the score. CONCLUSION: The study shows that anesthesiologists lack adequate knowledge about OSA. The total correct score ratio was 62%; when they managed an OSA patient, the positive attitude score is mostly below 50%. They have low confidence about OSA patients. It is necessary to develop special training programs on OSA regularly for anesthesiologists after graduation.

[Knowledge and attitude of clinicians to pediatric obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the knowledge and attitude of clinicians in the departments of pediatrics and otolaryngology to pediatric obstructive sleep apnea hypopnea syndrome (OSAHS), since in China, the clinicians in these two departments had closest relationship with the diagnosis and treatment of OSAHS in children. METHODS: A validated questionnaire from USA which was the obstructive sleep apnea knowledge and attitudes questionnaire in children (OSAKA-KIDS) was used and permission by original author. The questionnaire was mailed to ENT doctors and pediatricians in 43 public hospitals in Shandong province. RESULTS: OSA-KIDS in Chinese version was re-tested by 30 physicians, r = 0.92. Totally, 391 valid questionnaires (87.7%) were returned. Average of correct rate (x(-) ± s) in 18 knowledge items was 64.1% ± 19.1%. Cronbach's α coefficient was 0.76. There was no difference between ENT doctors and pediatrics in total knowledge score. However, there was significant difference in below 2 questions: ENT doctors had more correction in answer "nearly 2% of children have OSAHS" and pediatrics had more correction in answer "pediatric OSAHS may be associated with pulmonary hypertension". Only 24.3% clinicians correctly know the degree of snoring (mild to severe) was not correlated with the severity of obstructive apnea in children. Only 16.1% could correctly answer the question about cardio-respiratory monitor could not reliably detect both central and obstructive apnea in infant. Cronbach's α coefficient was 0.72 in 5 items which was about importance of disease and self-evaluation in confidence. While more than 90% clinicians stated that "As a clinical disorder OSAHS is important or very, extremely important". However, among them, only about 36% felt confident in identifying or managing children with OSAHS. Total knowledge score about OSAHS was not different by gender or specialty (P > 0.05), but more knowledge was associated with more positive attitudes overall (P < 0.05) and more elder in age or longer years in practice (r = 0.384, P < 0.0001). CONCLUSIONS: It should be paid more effort to elevate the knowledge and attitude about pediatric OSAHS in pediatricians and otolaryngologists.

Bilateral congenital choanal atresia and osteoma of ethmoid sinus with supernumerary nostril: a case report and review of the literature.

INTRODUCTION: Congenital choanal atresia is a relatively rare deformity, especially bilateral congenital choanal atresia. We report a case of bilateral congenital choanal atresia in a 22-year-old Chinese man, who was also diagnosed with congenital right accessory nasal deformity, osteoma of his left ethmoid sinus and congenital keratoleukoma of his right eye. CASE PRESENTATION: A 22-year-old Chinese man presented with mouth breathing, sleep snoring and difficult feeding after birth, with no olfactory sensation. Three-dimensional computed tomography revealed bilateral choanal atresia and a high density bony shadow in his left ethmoid sinus that extended to his left frontal sinus. CONCLUSIONS: Choanal atresia is often accompanied by other congenital abnormalities. To the best of our knowledge, this is the first report of choanal atresia accompanied by congenital accessory nasal deformity and congenital keratoleukoma.

Preservation of laryngeal functions in surgical treatment of pyriform sinus carcinoma.

CONCLUSION: The tumor's grade, rather than the tumor's location, was related to the opportunity of preserving laryngeal functions in patients with pyriform sinus cancer. The survival rate decreased significantly with the increase of tumor grade or node grade. Preservation of laryngeal functions is a safe and promising method without compromising the survival rate of patients with pyriform sinus cancer. OBJECTIVE: Surgical resection of pyriform sinus carcinoma has a profound influence on the preservation of laryngeal functions. The purpose of this study was to assess the safety and efficacy of the surgical treatment of pyriform sinus carcinoma in the preservation of laryngeal functions without compromising the survival rate. METHODS: Two hundred and thirty patients with pyriform sinus cancer had been operated from March 1978 to December 2002. Of them, 158 cases had been operated with the preservation of laryngeal functions and 72 cases had been undergone total laryngectomy. In addition, 216 cases had received adjuvant postoperative radiotherapy. All cases were followed up for 6-12 months (mean 51 ± 26) after surgery. The survival rate was calculated on the basis of Kaplan-Meier analysis, and the factors that influenced the survival rate of patients with and without preservation of laryngeal functions were analyzed with the log-rank test. RESULTS: Laryngeal functions were preserved completely (speech, respiration, and deglutition) in 70.9% (112/158) cases, and partially (speech and deglutition) in 29.1% (46/158) cases. The 3- and 5-year survival rates were 75.4% and 59.0%, respectively, for the group with laryngeal function preservation, and 58.6% and 41.5%, respectively, for the group without preservation. There was no statistically significant difference in the survival rate between the two groups within the follow-up period (p > 0.05). Increase in the tumor grade resulted in a proportional decrease of patients with preservation of laryngeal function (p < 0.05). Increase in the tumor grade (p < 0.05) or node grade (p < 0.05) also led to significant decrease in the survival rate. The location of the primary lesions (the lateral wall or medial wall of the pyriform sinus) showed no significant influence on either the opportunity for preserving laryngeal functions (p > 0.05) or survival rate of patients (p > 0.05).

[An analysis of the cause and countermeasure of death of patients with severe obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To discuss the causes and countermeasures of death of severe obstructive sleep apnea hypopnea syndrome (OSAHS) patients undergoing tests or treatment. METHODS: A retrospective study of the data of six patients with severe OSAHS who died undergoing tests or treatment in 6 hospitals was conducted. RESULTS: Among the 6 patients, overly fat were found in 2 cases, hypertension in 2 cases, cardiac diseases in 2 cases, abnormal pulmonary function or chest X-ray in 2 cases, diabetes in 2 cases, while 2 cases had no above positive finding. Three patients did not have polysomnography (PSG). One patient died during PSG test. Two patients' apnea hypopnea index (AHI) were 56 times/h and 82 times/h respectively. The causes of death were as follows, two patients died of airway obstruction and unsuccessful tracheal intubation before uvulopalatopharyngoplasty (UPPP) operation. One died of encephaledema in long-term coma due to airway obstruction, long time poor oxygenation and unsuccessful tracheal intubation with muscle relaxants before hemostasis procedure for treating postoperative hemorrhage. One patient whose preoperative pulmonary function showed increased airway resistance died of cardiac and respiratory arrest after tracheal extubation when UPPP surgery finished. One who was found to have potential cardiac and pulmonary disorder died of cardiac arrest when doctors were replacing his tracheal intubation with a cannula, before the tube replacing procedure the patient was conscious. One who had hypertension, coronary heart disease, diabetes mellitus and adiposis suffering from respiratory acidosis with his electrocardiogram showing a level-three heart function died of cardiac arrest with repeated apnea during PSG monitoring. CONCLUSIONS: OSAHS patients with severe complications should be treated extremely carefully. The indication of surgery should be strictly observed. OSAHS patients can not undergo surgery until their cardiopulmonary functions and general conditions are improved.

[Obstructive sleep apnea hypopnea syndrome: surgical complications and strategy for avoidance].

OBJECTIVE: To analyze the surgical complications in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and discuss the risk factors and preliminary strategies for prevention of complications. METHODS: From September 1998 to March 2007, 653 OSAHS patients confirmed by polysomnography were treated by different surgical approaches according to their obstructive sites, which included uvulopalatopharyngoplasty (UPPP) in 586 cases, nasal surgery in 104 cases/times, hyoid suspension surgery in 53 cases/times, respectively or at the same time. Local anesthesia was used in 294 cases and general anesthesia in 359 cases. Two hundreds and seventeen cases were treated by continuous positive airway pressure (CPAP) 3 to 7 days pre-operation and 2 to 3 days post-operation. RESULTS: Perioperative complications were found in 57 OSAHS cases (93 times), the incidence of peri-operative complications was 8.7% (57/653), including respiratory problems in 19 cases/times and 1 death occurred during inducing stage in general anesthesia. Profuse bleeding was encountered in 9 cases/times during operation and primary and secondary bleeding in 27 cases/times, cardiopathy and hypertension crisis in 31 cases/times and cerebral stroke and hemiplegia in 1 case, reactive somnolence in 3 cases/times and reactive hyperglycemia in 3 cases/times. Data were analyzed by the multivariate logistic regression model. The results showed that the complications were significantly reduced after CPAP treatment during peri-operative stage and increased accompanied with patients' hypertension, choice of general anesthesia, BMI and AHI. All patients were followed-up more than 1 year. After UPPP, 23.9% cases (140/586) had sensation of foreign body in pharynx and alleviated in 6 to 12 months. Scar tissues in oropharynx in 7 cases, nasopharyngeal stenosis in 1 case, atrophy rhinitides and atrophy pharyngitis in 3 cases, nasopharyngeal un-closure and long-term nasopharyngeal reflex in 3 cases. Conclusions Peri-operative complications are more common in obese and severe OSAHS patients, especially when they accompanied with hypertension. The corresponding strategies should be taken to reduce complications in OSAHS surgery, which include controlling the hypertension effectively, performing CPAP treatment actively, cooperating with interdisciplinary doctors, monitoring closely after operation. It is important to reduce surgical sequelae through improving surgical skills and not enlarging the surgical scale blindly.

[Diagnosis and surgical management of carotid body tumor as well as blood vessel prosthesis' role].

OBJECTIVE: To analyse the diagnostic and therapeutic aspects of carotid body tumor (CBT). METHODS: Seven patients with CBT had been hospitalized between 2003 and 2006. The clinical data was analyzed retrospectively. The preoperative evaluation included angiography in 7 patients. Most of them had an asymptomatic cervical lateral mass. Only one patient had the hoarseness and buckling and was given radiation therapy alone. Six of seven patients with carotid body tumour underwent surgery. Simple tumor excision was accomplished in 4. Carotid artery resection with the tumor was required in 2 patients and in the both, interposition of a 7 mm polytetrafluoroethylene graft was performed . During the resection, temporary carotid shunt was required in the two patients. RESULTS: All tumors by surgery were identified as carotid paragangliomas without evidence of malignancy. There was no mortality and no hemiplegia. After surgery, temporary cranial nerve dysfunction was noted in one case. In the follow-up period of 2 months to 2 years, no recurrent disease occurred. The patient's tumor who accepted radiotherapy was in the stable stage under the half year follow up, and the follow up would be further continued. CONCLUSIONS: With non-invasive investigation and arteriography it was possible to obtain an early and precise diagnosis. The surgical management was the major treatment of these tumors. The pattern of operation should be chosen according to the relation of tumor and carotid. The decision to perform simple tumor excision or additional arterial resection was based on diagnostic preoperative and after the arterial resection the polytetrafluoroethylene graft would be used for carotid reconstruction.

[Primary evaluation of the indications of uvulopalatopharyngoplasty].

OBJECTIVE: To evaluate the indications of uvulopalatopharyngoplasty (UPPP) and clinical staging for oropharyngeal narrow in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: Sixty-six OSAHS patients were retrospectively analyzed, the data of physical examination and clinical staging for oropharyngeal narrow were built based on body mass index (BMI), palate-tongue position, tonsil sizes and hypertrophy degree in lateral side of oropharynx. The patients who had palatine-tongue position in degree 1 to 2 (no significant tongue enlargement) were defined as stage I (32 cases). The patients who had palatine-tongue position in degree 3 to 4 (tongue enlargement) were defined as stage II (34 cases). Among them, the patients with tonsil sizes 0 to 1 were stage I a (5 cases) and stage IIa (10 cases), another group with tonsil size 2 to 4 were stage I b (27 cases) and stage II b (24 cases), respectively. The indications of UPPP were evaluated according to the results of polysomnography (PSG) before and after operation. RESULTS: PSG in 1 to 2 years after operation showed: the surgical efficiency of UPPP had not any difference (P > 0.05) among different groups with the severity of OSAHS(labeled in preoperational AHI and LSaO2). Surgical results was better in patients with BMI < 30 kg/m2 (P = 0.023). Success of operation was defined as postoperational AHI <20/h and reduced more than 50% compared to preoperational AHI and symptoms alleviated significantly. Successful rates of UPPP in stage I b (70.4%, 19/27 cases) were statistically higher than that of other groups (I a:0%; I b:70. 4%; II a:20.0%; II b: 16.7%). CONCLUSIONS: Clinical staging system for oropharyngeal narrow is based on palate-tongue position and tonsil size. It is helpful to choose the surgical indications of UPPP for patients with OSAHS. It is the best UPPP indication for stage I b patients who had no tongue enlargement (palatine-tongue position 1 to 2) and accompanied with enlargement of tonsil size (in degree 2 to 4) and their sleep breathing disorder could be alleviated through UPPP.

[Quality of life survey in children with obstructive sleep apnea hypopnea syndrome before and after operation].

OBJECTIVE: To evaluate the influence of OSAHS in quality of life (QOL) for children and its changes before and after surgery. METHODS: Pediatric OSAHS disease-specific quality of life survey (OSA-18) and polysomnography (PSG) were used to analysis in 54 cases within 4 weeks before surgery. They were treated by tonsillectomy in 8 cases and adenoid tonsillectomy in 32 cases, adenoidectomy alone in 14 cases and were followed up in 12 to 18 months post-operation. RESULTS: The impact of pediatric OSAHS on QOL was severe in 61.11% patients. There were significant statistically correlation between OSA-18 and AHI, LSaO2 before surgery. After surgery, the total scores of QOL were improved in 75.92% cases in general. The domains of sleep disturbance in 88.89% cases, caregiver concerns in 74.07% and physical suffering in 70.37% were significantly improved, respectively. CONCLUSIONS: Pediatric OSAHS had severely influenced in quality of life of children. There are significant correlations between the survey in quality of life of pediatric OSAHS (OSA-18) and the objective data in PSG. OSA-18 can be a valuable measure in clinical diagnosis and treatment follow-up.

[Treatment of pediatric obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To evaluate treatment options of pediatric obstructive sleep apnea hypopnea syndrome (OSAHS) and their curative effect. METHODS: In this study, there are 59 confirmed pediatric obstructive sleep apnea hypopnea syndrome cases diagnosed by polysomnography (PSG). Among them, 54 cases were treated by tonsillectomy or/and adenoidectomy directed by transoral endoscopy. Continue positive airway pressure (CPAP) was used for 2 cases in long-term. Three cases were treated with other conservative therapy. OSA-18 (quality of life for children with obstructive sleep apnea 18 items) was adopted as a disease-specific quality-of-life follow-up survey before and after treatment. RESULTS: During perioperation period, no postoperative bleeding or acute respiratory obstruction occurred. Follow-up sleep study was carried out 12-18 months postoperatively, no complications of velopharyngeal insufficiency, nasopharyngeal stenosis or residual adenoid were found. OSA-18 scores showed that quality of life had been significant improved after operation in 76.3% (45 cases), sleep disturbance in 88.1% (52 cases) and physical symptoms in 67.8% (40 cases). The pressure level of long-term CPAP in 2 cases was about 5.6-7.8 cmH2O. 3 cases were slightly improved treated with conservative therapy. CONCLUSIONS: Surgical removal of upper airway obstruction caused by enlargement of tonsil and adenoid is one of the most effective treatment for pediatric OSAHS. Fibrous endoscopy and cephalometric analysis are helpful to confirm surgical indication. The advantages of transoral endoscopy directed adenoidectomy are as follows: clear and direct visualization, complete removal, without damaging of the peripheral structures.

[Diagnosis of pediatric obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To discuss the clinical feature and diagnosis of pediatric obstructive sleep apnea hypopnea syndrome (OSAHS) and analyze characteristics of polysomnography. METHODS: Cephalometric analysis, fibrous endoscopic examination and sleep breathing studies were performed in 49 cases with suspected complaints and signs. RESULTS: Most of them had marked history about snore, sleep apnea and signs of upper airway obstruction caused by enlargement of tonsil and/or adenoid. Polysomnography (PSG) was given to 41 cases who was proved 1 case with primary snore, 5 cases with upper airway resistance syndrome, 35 cases with OSAHS. Another 8 cases with OSAHS were diagnosed by Autoset I studies. CONCLUSION: Many features of pediatric OSAHS are different from adult OSAHS. The common symptom of pediatric OSAHS include snore, restless sleep, struggling to breathe, abnormal paradoxical chest/abdomen motion, mouth breathing, failure-to-thrive. Obesity and excessive daytime sleepiness are little present. Severe cases may be associated with cor pulmonale. PSG play an important role in exact diagnosis of pediatric sleep related breathing disorder. The results demonstrate that pediatric OSAHS are characterized by partial upper airway obstruction, more or less apnea and associated with staged desaturation. They have little sleep structure disorder and difficulty breathing are not associated with arousal. Apnea hypopnea index (AHI), lowest oxygen saturation (LSaO2) and desaturation index below 90% (SIT90%) are very important factors to measure about serious degree of pediatric OSAHS.