Identification and genetic analysis of new mutations in EYA1 gene of BOS syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis. Methods: Clinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing. Results: There were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) in EYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family. Conclusions: A novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.

Analysis of genetic characteristics in two Chinese children of type Ⅱ Waardenburg syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.

The Pubmed Bibliometric Analysis of Trend in the Research on Age-related Hearing Loss / 听力学及言语疾病杂志

Objective This study aimed to define research status of age -related hearing loss ,and provide the basis and direction for future research .Methods We have retrieved all relevant literatures on age -related hearing loss from Pubmed ,and conduct an objective analysis of the existing literatures by Bibliometric analytics and co -word analysis method using co -occurrence bibliographic information mining system and SPSS22 .0 software for data analysis .Results There were a large number of articles and journals about presbycusis and age -related hearing loss .Many countries were involved in the research .Literatures and core authors were mainly from developed coun‐tries such as Europe and the United States .The quantity and quality of Chinese literatures were in a leading position in Asia .The researches focused on the common characteristics of patients ,the epidemiology ,characteristics of hear‐ing ,treatment and laboratory studies .There were some new research directions in recent 5 years ,such as factors as‐sociated with the younger ages before developing presbycusis ,standard design and use of questionnaires ,prevention and control .Conclusion Age-related hearing loss will continue to be a hot topic with growing focus on micro and macro development of multi -disciplinary cooperation .The penetration will be the trend for the future research while the prevention will become a new focus of research .

Relationship among allergic rhinitis, regional pollens and meteorological conditions in Kunming area / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the species, quantity and diffusion of allergenic pollens as well as the relationship among allergic rhinitis (AR), pollen species and meteorological conditions in Kunming area.</p><p><b>METHODS</b>The exposure film was used to investigate the species of airborne pollen, the total number of these pollens during December 2009 to November 2010 by means of gravitational sedimentation, at the same time, AR patients were registered. The species of allergic pollen in Kunming area during the same period, and the statistic analysis was made with the meteorological elements, using the correlation analysis methods of Excel for data analysis.</p><p><b>RESULTS</b>From December 2009 to November 2010, a total of 60 exposure films of pollen species was found, including 26 147 pollens. The annual airborne pollen showed two scattering peak, respectively: February to April and September to October; the number of advantage pollen was 17 species. The number of year-round drifting pollen was 13 species while 2 species showed two peaks on spring and autumn. There was another 26 new species added to the results of 2009-2010, compared with 1987-1989, while the original 12 species were not seen. The drifting peak was the same. The number of allergen intradermal tests (AIT) positive AR patients was positively correlated with 16 pollen species, respectively, oleaceae, alnus nepalensis, walnut, palm, pig weed, fennel, Amaranthaceae, artemisia, rosa, Albizia julibrissin Durazz, gramineae, castor, Fraxinus L, populus, Morus alba L, hemp humulus, (r value were 0.689 7, 0.550 1, 0.742 1, 0.755 2, 0.771 2, 0.663 3, 0.556 1, 0.568 3, 0.659 8, 0.607 4, 0.834 7, 0.664 3, 0.745 9, 0.634 7, 0.718 3, 0.777 2, all P < 0.05). The population of AIT positive AR patients was positively correlated with average temperature, average wind speed and other meteorological factors (r values were 0.552 0, 0.883 5, both P < 0.05), and was negatively correlated with average relative humidity (r = -0.714 7, P < 0.05).</p><p><b>CONCLUSIONS</b>Kunming had a large number of airborne pollen species which showed two peaks annually, respectively, spring and autumn. The relationship among the number of AIT positive AR patients, the meteorological factors and the number of airborne pollen were close.</p>

The quantification and significance of muscle segment homeobox gene Msx2, human topoisomerase II-α, HPV16 and VEGF in sinonasal inverted papilloma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the quantification and significance of Msx2, topoII-α; HPV16 and VEGF in sinonasal inverted papilloma(SNIP), to study the correlation among the four factors,and to discover the relationship between Msx2 and topoII-α in the process of SNIP malignant transfomation.@*METHOD@#Real-time quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect the expression of Msx2, topoII-α, HPV16 and VEGF in 13 cases of sinonasal inverted papilloma (SNIP), 10 cases of sinonasal squamous cell carcinoma(NSCC) and 10 cases of inflammatory nasal polyp paraffin (INP)tissues. According to the pathology results SNIP were divided into mild dysplasia, moderate dysplasia and severe dysplasia. All the data were analysised by SPSS17. 0, P<0. 05 was refered to statistically significant difference.@*RESULT@#The mRNA level of Msx2, topoII-α, VEGF and HPV16 in SNIP, NSCC tissues were significantly higher than in the INP tissues (P<0. 05). The expression differences of Msx2, topoII-α, HPV16 and VEGF mRNA level in SNIP tissues which were divided into three groups according to their pathological results,were all statistically significantly different between any two of the three groups (P< 0. 05). Using Pearson correlation coefficient analysis,we found positive correlation between any two of the mRNA level of Msx2, topoII-α, VEGF and HPV16 (P<0. 05).@*CONCLUSION@#Msx2 and topoII-α may play an important role in the process of SNIP Malignant transformation,which may be new targets for gene therapy of SNIP and NSCC.

Research on 3-D reconstruction of sphenoid sinus in children and adolescents in Yunnan region / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To research the correlation between development of sphenoid sinus and age in normal children and adolescents by 3-D CT images.@*METHOD@#Review of CT images of the skulls of 120 children and adolescents aged 0~20 years old. They were divided into five groups. Then reconstructed 3-D shape of the sphenoid sinus, and measureed the maximal anteroposterior diameter, longitudinal diameter, and transverse diameter of the bilateral sphenoid sinus by the 2-D and 3-D approach respectively, then process statistical analysis.@*RESULT@#Pearson analyses revealed a positive correlation between various diameters of sphenoid sinus measured by 2-D and 3-D approach and age (P<0. 05).@*CONCLUSION@#The development of sphenoid sinus has a linear correlation with age, and increases with age and growth in Yunnan region. It helps to know the three-dimensional CT images of the sphenoid sinus in children and adolescents by Simplant software, thereby allow the clinicians to understand the current situation of the development of sphenoid sinus. Meanwhile, it contributes to preoperative evaluation of sinus problems.

Short-term efficacy of standardized medication offer chronic rhinosinusitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the efficacy of standardized medication for patients with chronic rhinosinusitis.@*METHOD@#According to the diagnosis and treatment guidelines on chronic rhinosinusitis formulated in 2008, by means of prospective study, we studied 54 patients suffering from chronic rhinosinusitis treated with standardized medication including, a combination of local intranasaI corticosteroids, macrolides, mucus discharging agent and nasal irrigation treatment and followed up for 3 months. Visual analogue scale (VAS), sino nasal outcome test-20 Chinese version scales (SNOT-20 CV), Lund-Mackay CT and Lund-Kennedy endoscopy methods were employed to conduct the subjective and objective assessment and comprehensively evaluate the clinical efficacy before and after treatment.@*RESULT@#(1) After three months of standardized medication, the patients' total scores of VAS, SNOT-20 CV, CT and endoscopy were improved significantly compared with those before-treatment (P < 0.01 for all these scoring systems). (2) There was statistically significant difference between the clinical efficacies of chronic rhinosinusitis patients with and without nasal polyps groups (P < 0.01). After 3 months of standardized medication, the effective rates of the CRSwNP group evaluated by subjective assessment and CT evaluation were 66.7% and 94.4% respectively, while those of the CRSsNP groups were 91.7% and 97.2% respectively. (3) Betwecn CRSwNP and CRSsNP groups, there was no significant difference in the improvement rate or inefficiency rate in subjective assessment except for the cure rate, while there were significant differences in both cure rate and improvement rate in CT evaluation. (4) The CRS patients' self-testing-based questionnaires results showed positive correlation with objective assessments.@*CONCLUSION@#The standardized medication with combination of intranasal local glucocorticoid, macrolides (14-membered ring), the mucus discharging agent and nasal irrigation on CRS was effective.

Expression and Significance of Toll-like receptor-2 and Heme oxygenase-1 in Recurrent Nasal Polyps / 昆明医科大学学报

Objective To investigate the expression and significance of TLR-2 and HO-1 in recurrent nasal polyps,and to discuss the relationship between the expression and the recurrence of nasal polyps. Methods The immune protein imprinting technology was used to detect the protein expression of TLR-2 and HO-1 in 20 cases of recurrent nasal polyps,20 cases of nasal polyps and 20 cases of normal mucosal tissue in control group, and the relationship between the two proteins were analyzed. Results Expression levels of TLR-2 and HO-1 in the tissues of the recurrent nasal polyps had statistically significant difference with nasal polyps group ( <0.05) . Expression levels of TLR-2 and HO-1 in the tissues of the nasal polyps had statistically significant difference with normal nasal mucosa tissues ( <0.05) .The expression of TLR-2 and HO-1 had significant correlation in each group ( <0.05) .Conclusion TLR-2 and HO-1 plays an important role in the recurrence mechanism of nasal polyps, and both of them may be as objective indicators for postoperative follow-up of patients with recurrent nasal polyps and judging the recurrent trend.

Prevalence of sensitization to aeroallergens in 1 893 patients with allergic rhinitis in Yunnan / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate which aeroallergens were prevalent in patients with allergic rhinitis in Yunnan.@*METHOD@#Retrospective analysis of the medical records of intradermal test performed in 1893 AR patients. The samples were divided into four age groups: 4-17-year-olds, > 17-35-year-olds, > 35-50-year-olds and > 50-70-year-olds. According to gender,the samples were decided into two groups: the males and the females. The positive rate of aeroallergens were compared among the groups.@*RESULT@#(1)The total positive rate of intradermal test was 70.1%. The top ten allergens were as follow: dermatophagoides pteronyssinus, dermatophagoides farina, house dust, pollen of the summer and autumn, alnus nepalensis, chenopodiaceae, mugwort, poaceae, brassica and cockroach. (2) In all groups,patients with triple positive allergens were the most common,followed by dual positive allergens and single positive allergen. (3) Among the top ten allergens, the top three positive ones in all groups were dermatophagoides pteronyssinus, dermatophagoides farina and house dust. And there were significant differences between 4-17-year-olds group and the other age groups (P < 0.01). (4) There was no significant difference between male and female patients in distribution of aeroallergens except House dust and mite.@*CONCLUSION@#The most common allergen in patients with allergic rhinitis in Yunnan is mite,the follow are pollen of the summer and autumn, alnus nepalensis, chenopodiaceae, mugwort, poaceae, and brassica. The distribution of aeroallergens are different among the age groups, but has no evident correlation with gender.

The relationship between three-dimensional morphology of maxillary sinus and maxillary sinusitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#A three-dimensional morphology of the maxillary sinus was reconstructed. We studied the relationship between sinusitis and three-dimensional morphology, volume as well as gasification coefficients.@*METHOD@#One hundred and fifty adult subjects were selected in this study, and divided into three groups: normal bilateral maxillary sinus, unilateral maxillary sinusitis and bilateral maxillary sinusitis, with fifty cases in each group. Use Siemens helix CT for sequential scanning of the nasal-sinus. After scanning, the DICOM data was recorded in DVD-R and transferred into another computer for reconstruction and measurement.@*RESULT@#The volume of the normal maxillary sinus group was (15 018.64 +/- 473.36) mm3. The volume of the maxillary sinusitis group was (14 971.86 +/- 360.93)mm3. There was no significant difference between the values of volumes for the normal maxillary sinus group and maxillary sinusitis group. The gasification coefficient was 0.345 +/- 0.071 for the normal maxillary sinus group, 0.252 +/- 0.057 for the maxillary sinusitis group. There was significant difference between the two groups.@*CONCLUSION@#Maxillary sinus reconstruction permits more vivid visualization of the three-dimensional structure and three-dimensional shape of the maxillary sinus. The occurrence of the maxillary sinusitis is closely related to the three-dimensional shape of the maxillary sinus and the gasification coefficient measured. The more regular the three-dimensional shape of the maxillary sinus, with the gasification coefficient >0.300, the lower the probability of the maxillary sinusitis. Otherwise, the probability increases. Adult inflammation of maxillary sinus may be originated from a relatively larger volume of maxillary sinus in childhood and adolescence.

Genetic testing and mutation analysis for the cochlear implantation children and their normal auditory phenotype parents / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the characteristics and significant of mutations of GJB2 gene, SLC26A4 gene and mitochondrial 12S rRNA in deaf children who received cochlear implantation (CI) in Yunnan and to provide the data for diagnoses and research of recovery in C1 children.@*METHOD@#Genomic DNA was extracted from the peripheral blood samples collected from 46 children and their parents (110 cases). All the children received the CI. Their parents had normal auditory phenotype. PCR was performed and the products were sequenced by automated DNA sequencer to detect the hot spots of mutations.@*RESULT@#The detection rates of GJB2 235delC (13.0%) and 109G>A (24.0%) mutations were significantly higher than other mutations. SLC26A was the secondary major mutation (13.0%). We found out that no patient carried the mitochondrial 12S rRNA mutations. Leukoencephalopathy, hyperbilirubinemia and hypoxic-ischemic injure were disclosed in 7 patients (15.2%). The rate of mutations in parents was 36.0% (23/64). There had no difference between Han and other racial minorities (P>0.05).@*CONCLUSION@#The CI recipients in Yunnan with a high frequency of 235 delC and 109 G>A mutation, IVS7-2A>G (6.5%) is also a common mutation related hearing loss; aminoglycoside antibiotics may not be the main reason which induced congenital deaf in CI children; environment facts was suggested to contribute another important cause. The hot-spots gene screening for the C1 children could offer an accurate genetic counseling for early diagnosis and treatment, it also provide evidences for the clinical analysis between mutations and curative effect.

Expression and significance of Msx2 and topo II-alpha in sinonasal inverted papilloma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression and significance of muscle segment homeobox2 (Msx2) and topo II-alpha in sinonasal inverted papilloma (SNIP), and the relationship in the process of malignant transformation of SNIP.@*METHOD@#Immunohistochemical method was used to detect the expression of Msx2 and topo II-alpha in 32 cases of SNIP, 30 cases of inflammatory nasal polyp (INP) and 30 cases of SNIP with carcinoma. According to the pathology results, SNIP were divided into mild atypical hyperplasia, moderate atypical hyperplasia and severe atypical hyperplasia.@*RESULT@#The mean optical density of Msx2 in SNIP and SNIP with carcinoma tissues were 0.2183 +/- 0.0598 and 0.2521 +/- 0.0761,which were significantly higher than 0.1878 +/- 0. 0372 in the INP tissue (P<0.05 or 0.01). The mean optical density of topo II-alpha in SNIP and SNIP with carcinoma tissues were 0.2303 +/- 0.0397 and 0.2666 +/- 0.0483, which were significantly higher than 0.1978 +/- 0.0388 in the NIP tissue (P<0.01). There were significant difference of Msx2 and topo II-alpha in SNIP between any two of the three groups divided according to pathological morphology (P<0.01 or 0.05). The expression of Msx2 and topo II-alpha in SNIP were positively correlated (P<0.05).@*CONCLUSION@#Msx2 and topo II-alpha may play an important role in the occurrence and development of SNIP. So it can be used as new therapeutic targets.

Clinical application of computer-aided electromagnetic imaging navigation in nasal endoscopic surgery / 中国医师进修杂志

Objective To evaluate the clinical application of computer-aided electromagnetic imaging navigation in nasal endoscopic surgery.Methods Twenty-two cases of nasal endoscopic surgery with intraoperative imaging navigation were retrospectively reviewed,including 16 cases of sinusitis with or without polyp;5 cases of nasal inverting papilloma; 1 case of maxillary capillary hemangioma.All cases were operated with computer-aided electromagentic imaging navigation and nasal endoscope.Results The preoperative preparing time would take 4-10 minutes.In 22 cases,the localization accuracy between 3-D image landmarks of navigation system and actual anatomical landmarks was less than 1 mm.The optic nerve and other anatomical landmarks could be orientated accurately in intraoperative procedures.No complication occurred.Conclusions Nasal endoscope combined with computer-aided electromagnetic imaging navigation provides accurate anatomical localization of nasal cavity,sinuses and anterior skull base.It could improve the effectiveness and decrease surgical complications,especially in complicated cases.

Radiological research of maxillary sinus development of children and adolescent without sinusitis in Kunming of Yunnan / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the maxillary sinus development and provide data for sinus surgery on children.@*METHOD@#Two thousand two hundred and thirty-eight children were randomly selected among those who underwent skull and nasal sinus CT scanning because of certain symptoms and signs. Patients were divided into eighteen age cohorts based on their age at the time of the scan. Anterior-posterior, transverse diameters and vertical height of the maxillary sinus were measured and statistically analyzed.@*RESULT@#The maxillary sinus volume was enlarging even in adult, hut the growth of maxillary sinus was relatively stable in adolescent. The difference of transverse and anterior-posterior diameters of maxillary sinus had no statistical significance between female and male (P > 0.05), while there was statistically significant difference in the vertical height of maxillary sinus (P < 0.05).@*CONCLUSION@#The results will aid the physicians when correlating the clinical and radiographic findings of pediatric patients who are being evaluated for sinus disease and potential surgical intervention.

The study on the association of the interleukin-4 receptor gene polymorphism with allergic rhinitis / 中国耳鼻咽喉头颈外科

OBJECTIVE To dectect the possible association between interleukin-4 receptor gene polymorphism and allergic rhinitis. METHODS The study was conducted in two different groups: patients with allergic rhinitis (the case group,n=50) and healthy people (the control group,n=40). The IL-4R Q576R polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study compared frequencies distribution of genotype and allele between the two groups,and calculated odds ratio (OR) of genotype. RESULTS IL-4R allelic frequencies showed significant difference between the two groups (x2=9.12,P