Endoscopic assisted adenoidectomy versus conventional curettage adenoidectomy: a meta-analysis of randomized controlled trials.

Adenoidectomy, surgical removal of hypertrophic adenoids, is a common operation in children worldwide. The purpose of this study was to compare the operative effectiveness, and included total operative time, blood loss and complications, between endoscopic assisted adenoidectomy and conventional curettage adenoidectomy. EMBASE, PubMed, Cochrane Library, and China National Knowledge Infrastructure and symposiums and review articles were used to choose relevant randomized controlled trials. A meta-analysis was performed to analyze the data for total operative time, blood loss and complications. Seven studies fit the inclusion criteria, and included 331 patients treated with endoscopic assisted adenoidectomy, and 251 patients treated with conventional curettage adenoidectomy. The meta-analysis demonstrated that compared with conventional curettage adenoidectomy, endoscopic assisted adenoidectomy had a shorter operative time (SMD -1.09; 95 % CI -1.29 to -0.90; p < 0.00001), less blood loss (MD -19.74; 95 % CI -22.75 to -16.73; p < 0.00001), and fewer complications (OR 0.15; 95 % CI 0.07-0.35; p < 0.0001). Endoscopic assisted adenoidectomy has advantages over conventional curettage adenoidectomy with regard to total operative time, blood loss and complications.

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway.

The present study aimed to investigate the mechanism by which Aurora kinase A (AURKA) promotes cell migration and invasion in head and neck squamous cell carcinoma (HNSCC). Transwell assays were performed to investigate the cell migration and invasion abilities of AURKA, whilst western blotting was used to analyze the protein expression in FaDu and Hep2 cells, each treated with pharmacological inhibitors. Following the inhibition of AURKA, Akt and focal adhesion kinase (FAK), the migration and invasion of the FaDu and Hep2 cells decreased. The expression of phosphorylated (p)-AURKA and p-FAK (Y397) was observed to decrease following FaDu and Hep2 cell treatment with VX-680, a small molecular inhibitor of AURKA. The expression of p-Akt and p-FAK (Y397) ceased following treatment with the Akt inhibitor triciribine. The expression of p-FAK (Y397) decreased, however, p-Akt expression did not change following treatment with the FAK inhibitor TAE226. In conclusion, AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC.

Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56(+) and cytoCD3(+) lymphocytes with aggressive clinical course, which is prevalent in Asian and South American populations. The molecular pathogenesis of NKTCL has largely remained elusive. We identified somatic gene mutations in 25 people with NKTCL by whole-exome sequencing and confirmed them in an extended validation group of 80 people by targeted sequencing. Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (21/105 subjects, 20.0%), tumor suppressors (TP53 and MGA), JAK-STAT-pathway molecules (STAT3 and STAT5B) and epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). As compared to wild-type protein, DDX3X mutants exhibited decreased RNA-unwinding activity, loss of suppressive effects on cell-cycle progression in NK cells and transcriptional activation of NF-κB and MAPK pathways. Clinically, patients with DDX3X mutations presented a poor prognosis. Our work thus contributes to the understanding of the disease mechanism of NKTCL.

[Comparison of HyperCVAD regimen and CHOP regimen in treating patients with lymphoblastic lymphoma].

OBJECTIVE: To compare the efficacy and safety of HyperCVAD regimen and CHOP regimen in treating patients with lymphoblastic lymphoma (LBL). METHODS: Seventy-five LBL patients were enrolled from January 2002 to October 2013, with 44 being treated with HyperCVAD and 31 being treated with CHOP regimen. The patients were followed up until 31 December 2013. Factors associated with the prognosis of the patients were analyzed using Logistic and COX regression models. RESULTS: The complete remission rate (73% vs. 23%) and overall response rate (91% vs. 46%) were both significantly higher in the patients receiving HyperCVAD regimen compared with those receiving CHOP regimen (P < 0.000 1). The follow-up lasted on average (median) 9.9 months (ranging from 1.3 to 41 months). The patients receiving HyperCVAD regimen had significantly longer overall survival (OS) (median 31.5 vs. 11 months, P = 0.012 7) and progression-free survival (PFS) time (median 16 vs. 5 months, P= 0.000 4) than those receiving CHOP regimen. Complete remission (CR) was negatively associated with increased lactate dehydrogenase (LDH, standard partial regression coefficent (beta) = -0.4793 and international prognostic index (IPI score > or = 3, beta = -0.691) in the patients receiving HyperCVAD regimen. The only significant predictor for survival was CR (relative risk (RR) = 0.146, 95% confidence interval (CI): 0.044-0.488). Common adverse events of the two regimens were bone marrow suppression, pulmonary infection, liver dysfunction and hemorrhage. Patients receiving HyperCVAD regimen were more likely to suffer from bone marrow suppression (100% vs. 84%) and severe pulmonary infection (27% vs. 3%) than those receiving CHOP regimen (P < 0.05). No patient died of those adverse events. CONCLUSION: Compared with CHOP regimen, HyperCVAD regimen can improve response rates and survival of LBL patients. Its higher level of pulmonary infection can be managed.

Novel modified surgical treatment of auricular pseudocyst using plastic sheet compression.

OBJECTIVE: To introduce a novel modified surgical procedure of excision of anterior cartilage of the pseudocyst along with plastic sheet compression for the treatment of auricular pseudocyst and ascertain the effect of the surgical modality of this disease. STUDY DESIGN: A retrospective study. SETTING: Medical college hospital. SUBJECTS AND METHODS: Eighty-seven auricular pseudocyst patients were subjected to excision of the anterior cartilage of the pseudocyst followed by plastic sheet compression from July 2006 to September 2013. The effects of the operation were evaluated. RESULTS: Eighty patients were males and 7 were females. The median age was 52 years old. The lesions of 86 patients were unilateral and only 1 was bilateral. The clinical features presented a hemispheric painless swelling, which was seen on the ventral side of the auricle, usually the scaphoid and triangular fossa. The average major axis of the pseudocyst was 1.7 ± 0.6 cm. The patients underwent excision of anterior cartilage of the pseudocyst along with plastic sheet compression. The average follow-up period was 51.9 ± 19.1 months. No recurrence was observed with this technique, and the appearance of the auricle was cosmetically acceptable. CONCLUSIONS: Our novel modified surgical procedure of excision of anterior cartilage of pseudocyst along with plastic sheet compression is an effective surgical management for the auricular pseudocyst. The advantages of a simple technique, a short-term therapeutic period, and no recurrence made the surgical procedure worth recommending as the definitive treatment of auricular pseudocysts.

Feasibility of using a dual-promoter recombinant baculovirus vector to coexpress EGFP and GDNF in mammalian cells.

Vectors that are capable of coexpressing two or more exogenous genes for in vitro and in vivo gene delivery are being increasingly studied. The aim of the present study was to explore the feasibility of using the pFastBac™ Dual vector, under the control of two cytomegalovirus (CMV) promoters with opposite directions, to coexpress enhanced green fluorescent protein (EGFP) and glial cell line-derived neurotrophic factor (GDNF) in the same mammalian cell. In the study, two promoters in the pFastBac Dual vector were replaced with CMV-EGFP and CMV-GDNF, whose directions were consistent with the initial directions. The pFastBac Dual-CMV-EGFP-CMV-GDNF plasmid was constructed and then transfected into human embryonic kidney (HEK) 293T cells. The recombinant virus, Bac Dual-CMV-EGFP-CMV-GDNF, was generated with the Bac-to-Bac Baculovirus Expression system and used to transduce HeLa cells. Immunofluorescence was applied to examine the coexpression of EGFP and GDNF in transfected or transduced mammalian cells, while western blot analysis was used to confirm the expression of GDNF in transduced HeLa cells. The recombinant plasmid was constructed and the recombinant baculovirus was successfully generated. Immunofluorescence observations demonstrated that EGFP and GDNF were simultaneously expressed in the same transfected HEK 293T cell and in a single transduced HeLa cell. Western blot analysis revealed that GDNF was expressed accurately in the transduced cells. Therefore, the pFastBac Dual vector is an efficient gene transfer vector that is able to coexpress two target proteins in mammalian cells and serve as a platform for combining reporter or/and therapy genes used in molecular imaging and dual-gene therapy. Thus, the current study presents a new coexpression strategy for dual-gene delivery in vitro and in vivo.

Merocel versus Nasopore for nasal packing: a meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the clinical outcomes, including efficacy and complications, of Merocel versus Nasopore as a nasal packing material after nasal surgery. METHODS: Relevant randomized controlled trials were identified from electronic databases (The Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure and Chinese Biomedical Database). Conference proceedings and references from identified trials and review articles were also searched. Outcome measures were pain during nasal packing, pain and bleeding upon packing removal, pressure sensation, nasal blockage, formation of synechiae, mucosal healing, and patients' general satisfaction. RESULTS: Seven randomized controlled trials met criteria for analysis. Compared with Merocel, Nasopore significantly reduced patients' subjective symptoms including in situ pain (pain experienced while packing is in place), nasal pressure, pain and bleeding during packing removal, and increased patients' general satisfaction with nasal packing. There were no significant differences in nasal obstruction, adhesion and mucosal healing between the Merocel and Nasopore groups. CONCLUSIONS: Preliminary evidence suggests that Nasopore may be superior to Merocel as a nasal packing material with regard to in situ pain, pain and bleeding upon removal, pressure, and general satisfaction and does not differ from Merocel in terms of nasal obstruction, tissue adhesion, and long-term mucosal healing.

Study on molecular imaging and radionuclide therapy of human nasopharyngeal carcinoma cells transfected with baculovirus-mediated sodium/iodine symporter gene.

The non-invasive imaging and radiotherapy by sodium/iodine symporter (NIS) gene transfer have been widely used for many experiments and some clinical studies. Baculovirus is an efficient tool for gene delivery into mammalian cells in vitro and in vivo. However, the applications of NIS and/or baculovirus in nasopharyngeal carcinoma (NPC) cells have not been reported yet. In this study, two recombinant baculoviruses expressing, respectively, NIS and green fluorescent protein (GFP), both under the control of the cytomegalovirus promoter (Bac-NIS and Bac-GFP) were successfully constructed. The infection efficiency and GFP fluorescence intensity of the human NPC cell line CNE-2Z infected by Bac-GFP at different setting of multiplicity of infection (MOI) were determined by flow cytometry. NIS protein expression was detected by indirect immunofluorescence. The 125I uptake and efflux of infected CNE-2Z cells by Bac-NIS were measured by a γ-counter. The cytotoxicity of baculovirus and sodium butyrate and inhibition of iodine uptake by NaClO4 were examined. The radioactivity and GFP fluorescence intensity in co-infected CNE-2Z cells by Bac-NIS and Bac-GFP were measured. Cell colony formation tests were conducted to evaluate the killing effect of Bac-NIS-mediated 131I. Based on the results, the transduction efficiency of Bac-GFP at the MOI of 200 or 400 reached 91.16 and 94.79%, respectively. NIS protein was expressed accurately on transfected CNE-2Z cell membranes and performed its normal function in iodine transport. Baculovirus had hardly any cytotoxic effects on infected cells, while relatively high concentration of sodium butyrate generated cytotoxicity. The correlation coefficient between the GFP fluorescence intensity and radioactivity in co-infected CNE-2Z cells was 0.917. Treatment coupled Bac-NIS with 131I killed the infected tumour cells dramatically in vitro. These results suggest that baculovirus is an effective vector of the gene delivery into CNE-2Z cells and NIS-mediated iodine transport is a potential approach for molecular imaging and radionuclide therapy of NPC.

Down-regulation of alpha-2u globulin in renal mitochondria of STZ-induced diabetic rats observed by a proteomic method.

AIM: To identify the changes of mitochondrial protein expression in diabetic renal parenchyma and to characterize their molecular functions and biological processes in diabetes. METHODS: Mitochondrial proteins extracted from renal parenchyma mitochondria of streptozotocin-induced diabetic rats and normal rats were separated by two-dimensional polyacrylamide gel electrophoresis and identified by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. RESULTS: Eleven proteins from 533 visualized protein spots displayed significant different expressions in mitochondria of diabetic kidneys compared with those in normal ones. Among these altered proteins, two proteins with the most obvious changes in protein expression were identified as alpha-2u globulin (mature protein, named A2) and its proteolytically modified form (named A2-fragment) respectively. These proteins were found in mitochondria of male rat renal parenchyma and were proved to be down-regulated in diabetic rats simultaneously. CONCLUSION: Our results suggest that down-regulation of alpha-2u globulin may be associated with an abnormal ß-oxidation of long-chain fatty acids during diabetes. The decreased expression of A2-fragment in renal mitochondria of diabetic nephropathy may reduce fatty acid ß-oxidation, which leads to a diminished energy supply from mitochondria to kidney tissue and the deposition of a large number of fatty acids in the kidney, ultimately causing and aggravating kidney damage. In conclusion, these findings may be helpful for understanding the molecular mechanism of diabetic nephropathy.

[Association of susceptibility to chronic rhinosinusitis with genetic polymorphisms of IL-4 and IL-10].

OBJECTIVE: To investigate the relationship between the promoter polymorphism of IL-4 and IL-6 and chronic rhinosinusitis (CRS). METHODS: One hundred and twenty-three patients with CRS and 239 healthy controls in Shanghai region were chosen in this study. The genotype of IL-4 gene -33T>C and -590C>T were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and the genotype of IL-10 gene -1082A>G was determined using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Statistical calculations were performed using SAS 8.2 software. RESULTS: Significant differences were found in genotype distribution of -33T>C and -590C>T between the CRS group and the control group (χ2=6.6013, P=0.0102, χ2=6.6013, P=0.0304), and -33T>C remained significant following application of the Bonferroni correction (P<0.025). The relative risks of CRS with -33T>C and -590C>T were 1.818(P=0.0236, 95%CI 1.084-3.050) and 1.838 (P=0.0147, 95%CI 1.127-2.997). There was linkage disequilibrium (LD) between the -33T>C and -590C>T. The coefficient of linkage disequilibrium (D') was 0.77 and the related coefficient (r2) was 0.54. The -33T/-590T haplotype was associated with CRS and the relative risk was 1.653 (P=0.0130, 95%CI 1.107-2.469). There were only two genotypes of IL-10 gene-1082A>G and the frequencies of the AA and AG genotypes were not different between the CRS and control groups. CONCLUSION: The promoter polymorphism of IL-4 -33T>C and -590C>T were associated with the susceptibility of CRS and the -33T/-590T haplotype was a risk factor for CRS, but there were no association between the -1082A>G and CRS.

[The association between genetic polymorphisms of IL-6 and the susceptibility of chronic rhinosinusitis].

OBJECTIVE: To investigate the relationship between the promoter polymorphism of IL6 (-174G > C, -572G > C and -597G > A) and chronic rhinosinusitis (CRS). METHOD: The case-control study consisted of 123 patients with CRS and 239 controls from a Chinese Han population from Shanghai. The genotypes of the subjects were determined by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. Besides, the concentrations of the totle immunoglobulin E (TIgE) and eosinophilic cationic protein (ECP) in the blood were also determined. RESULT: The -174G > C and -597G > A polymorphisms were not detected in this study population. Significant differences in genotype and allele frequencies of -572C/G were observed between CRS patients and control groups. In CRS patients, the CC, CG, GG genotype frequencies were 69.1%, 29.3%, 1.6%, C, G allele frequencies were 83.7%, 16.3%. In control group, the genotype frequencies were 55.2%, 42.3%, 2.5%, the allele frequencies were 76.4%, 23.6%, respectively. The -572CC genotype was associated with an increased risk of developing CRS (P < 0.05, OR = 1.932, 95% CI, 1.205-3.097). There was no significant differences in the concentrations of the TIgE and ECP among each genotype. CONCLUSION: IL-6 gene -572G > C polymorphism is associated with the susceptibility to CRS. CC genotype could be an independent risk factor.

[Analysis on clinical characteristics, treatments and prognostic factors of head and neck non-Hodgkin's lymphoma].

OBJECTIVE: To study the clinical characteristics, treatments and prognoses of the primary non-Hodgkin's lymphoma (NHL) in head and neck. METHOD: Clinical manifestations and clinicopathology characteristics of 107 NHL patients in head and neck were analyzed retrospectively. RESULT: The median age of patients with head and neck NHL was 54 years. The most commonly primary site was tonsil (29 cases, 27.10%), and the secondly primary site was nasal cavity (28 cases, 26.17%). The most common histologic subtype was diffuse large B cell lymphoma(46 cases, 42.99%), and the secondly one was NK/T cell lymphoma(24 cases, 22.43%). We found that the combination of rituximab was superior than that of chemotherapy alone. Prognosis depended on both IPI and histological subtype, and IPI was a more dangerous factor than histological subtype. CONCLUSION: The primary NHL is a common neoplasm in the head and neck region. Characteristic in age, primary site, histologic subtype, treatment and prognostic factors were helpful to understand and treat non-Hodgkin's lymphoma in head and neck.

[Endoscopic orbital decompression for thyroid-associated ophthalmopathy].

OBJECTIVE: To evaluate the therapeutic results of endoscopic orbital decompression for thyroid-associated ophthalmopathy. METHOD: The records of nine patients (twelve orbits) received endoscopic orbital decompression for thyroid-associated ophthalmopathy were analyzed for changes in visual acuity, intraocular pressure, proptosis, corneal ulceration and movement. The follow-ups ranged from two months to thirty-six months. RESULT: Twelve orbits (100%) had improvement in visual acuity (range 0.1-0.7). Ten orbits (83.3%) decreased in intraocular pressure (range 0.2-21.4 mm Hg). Eight orbits (66.70%) decreased in proptosis (one-five mm). The orbit with corneal ulcer was healed after decompression. Diplopia was cured in one of four patients. CONCLUSION: Endoscopic orbital decompression is a safe and effective procedure for the treatment of thyroid-associated ophthalmopathy.

CT and MR imaging patterns for pancreatic carcinoma invading the extrapancreatic neural plexus (Part I): Anatomy, imaging of the extrapancreatic nerve.

Pancreatic carcinoma is an extremely high-grade malignant tumor with fast development and high mortality. The incidence of pancreatic carcinoma continues to increase. Peripancreatic invasion and metastasis are the main characteristics and important prognostic factors in pancreatic carcinoma, especially invasion into the nervous system; pancreatic nerve innervation includes the intrapancreatic and extrapancreatic nerves. A strong grasp of pancreatic nerve innervation may contribute to our understanding of pancreatic pain modalities and the metastatic routes for pancreatic carcinomas. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful techniques for depicting the anatomy of extrapancreatic nerve innervation. The purpose of the present work is to show and describe the anatomy of the extrapancreatic neural plexus and to elucidate its characteristics using CT and MRI, drawing on our own previous work and the research findings of others.

[Suppression of Aurora-A by RNA interference inhibits laryngeal cancer Hep-2 cell growth].

OBJECTIVE: To investigate the effects of knockdown of Aurora-A by RNA interference on laryngeal cancer Hep-2 cell growth in vitro and in vivo. METHODS: A plasmid containing siRNA against Aurora-A was constructed and transfected into human laryngeal cancer cell line Hep-2. Measurements included the CCK-8 assay for viability and proliferation, Transwell assay for invasion, colony formation assay for cell anchorage-independent growth. Western blot and immunohistochemistry assay for protein expression. Tumorigenicity was observed in vivo. RESULTS: In Hep-2 cells transfected by Aurora-A siRNA (designated as siRNA-3), protein expression of Aurora-A was suppressed by 52%. In CCK-8 assay, absorbance value of siRNA-3 cells (3.268 ± 0.106, (x(-) ± s)) was lower than that of Hep-2 cells (3.722 ± 0.152, F = 17.634, P < 0.001). In Transwell assay, the average invasive cells per field in siRNA-3 cells (110.0 ± 18.0) was less than that in Hep-2 cells (236.0 ± 26.0, F = 26.462, P < 0.01). In colony formation assay, the average colony number of siRNA-3 cells (31.0 ± 6.6) was lower than that of Hep-2 cells (104.0 ± 14.0). The average tumor size in siRNA-3 group was (127.77 ± 174.83) mm(3), which was less than Hep-2 cell group (837.26 ± 101.80) mm(3), (F = 28.187, P < 0.001). Silencing of Aurora-A decreased the expression of focal adhesion kinase (FAK) and matrix metalloproteinase-2 (MMP-2), key regulators in cell adhesion and invasion. CONCLUSIONS: The knockdown of Aurora-A inhibits the growth and invasiveness of Hep-2 cells in vitro and in vivo, which may be a promising therapeutic strategy for LSCC.

[Association of IL-1beta gene -31T/C polymorphism with chronic rhinosinusitis].

OBJECTIVE: To investigate the relationship between polymorphism of IL-1beta gene 31T/C and chronic rhinosinusitis. METHOD: One hundred and twenty-three patients with chronic rhinosinusitis and 239 healthy controls were collected to determine the genotypes by polymerase chain reaction-restriction fragment length polymorphism. RESULT: There was significant difference in genotype and allelic frequencies between the CRS and control group (P < 0.05). -31CC genotype was an independent risk factor with CRS (P < 0.05, OR = 1.639). There was no significant difference in TIgE and ECP among these genotypes (P > 0.05). CONCLUSION: IL-1beta gene 31CC genotype may be an independent risk factor with chronic rhinosinusitis.

[Nasal anatomic abnormalities and bacterial infection in chronic rhino sinusitis].

OBJECTIVE: To study the relationship between nasal anatomic abnormalities and the bacteria infection status of maxillary sinus. METHOD: The anatomic abnormalities of 115 cases of maxillary sinuses were detected with the CT images and confirmed with chronic infection, which were divided into two groups: high anatomic abnormality group and low anatomic abnormality group. The sinusal contents were sent to bacteria culture, compare the bacteria infection rate and the distribution of bacteria between the two groups. RESULT: The bacteria positive rate of the high anatomic abnormality group and low anatomic abnormality group was 90.32% and 56.60% (P < 0.01) respectively. The contribution of gram-positive bacteria and gram-negative bacteria are 47.76% and 52.24% in high anatomic abnormality group, 62.16% and 37.84% in low anatomic abnormality group. CONCLUSION: Nasal anatomic abnormalities can improve the bacteria infectious rate of maxillary sinuses. High anatomic abnormality may more induces gram-negative bacteria infections,while low anatomic abnormality may more induces gram-positive bacteria infections.

[A computational fluid dynamics study of inner flow through nasal cavity with unilateral hypertrophic inferior turbinate].

OBJECTIVE: To investigate the anatomical influence of the hypertrophic inferior turbinate on computational fluid dynamics (CFD) model of unilateral hypertrophic inferior turbinate nasal cavity, and to analyze the bilateral detailed nasal airflow simulations under both inspiratory and expiratory phases in CFD model. METHOD: One male volunteer troubled with unilateral hypertrophic inferior turbinate accepted CT scan. CFD model was built by CT scans through Simplant 10.0 and ANSYS ICEM. Fluent 6.3.26 simulated the airflow of both nasal cavity in breathing rates 200 ml/s. RESULT: 1) In infraturbinal region, the cross-section area (CSA) of the nasal cavity with hypertrophic inferior turbinate was smaller than that in healthy side and the average area difference between two sides was 1.62 cm2. 2) In both inspiration and expiration phases, the hypertrophic infraturbinal produced a markable reduction in intranasal pressures drop along the full length of the infraturbinal region. The volumetric flow rate in the hypertrophic infraturbinal side was 50 ml/s, which equalled to one third of that in healthy side; Mean air speed in the anterior valve region was estimated to be 0.57 m/s at hypertrophic infraturbinal side and 1.83 m/s at healthy side during inspiration; More vortices happened in the hypertrophic infraturbinal side. CONCLUSION: The unilateral hypertrophic infraturbinal change the normal anatomy and influence the aerodynamic of nasal cavity, which is harmful to the functions of human nasal in ventilation, temperature accommodation and olfactory sensation.