Multi-center clinical study on the treatment of the low-middle frequency sudden hearing loss / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate and compare the short-term outcome of patients with low-middle frequency sudden deafness treated with alone or combination treatment.</p><p><b>METHODS</b>From August 2007 to October 2011, 205 patients with the diagnosis of low-middle frequency sudden deafness who were from 33 different clinical centers were recruited. All patients were followed up for four weeks from the initial examination. Patients were treated with steroid , Ginaton, batroxobin respectively, or Ginaton and steroid combination treatment.</p><p><b>RESULTS</b>The total effective rate was 90.73%. In Ginaton group, the total effective rate was 87.27%, 89.19% in steroid group, 87.80% in batroxobin group, and 95.83% in Ginaton and steroid group. Considering the total effective rate, there was no statistical difference between four groups (χ(2) = 7.98, P = 0.54). The clinical cure rate for steroid alone was 81.01%, Ginaton alone 76.36%, batroxobin alone 68.29%, and Ginaton and steroid combination treatment 80.56%. There were no clinically significant differences between the different treatments (P > 0.05).</p><p><b>CONCLUSIONS</b>The low-middle frequency sudden deafness tends to have a relatively favorable prognosis. The steroid played a good effect in the treatment. But different treatments either improving the microcirculation of inner ear or alleviating edema blood has undifferentiated results. Therefore the combination therapy may be more effective.</p>

Application and development of in vitro metabolism study at early drug discovery stage / 药学学报

Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.

Survival analysis for laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the survival rate and prognostic factors of laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy.</p><p><b>METHODS</b>One hundred and sixty-seven laryngeal carcinoma cases with no surgery, radiotherapy or chemotherapy were analyzed retrospectively. Survival rates were calculated by Kaplan-Meier product-limit method. With univariate analysis, comparisons among/between groups were performed using Log-rank test. Multivariate analysis was carried out using Cox proportional hazard model.</p><p><b>RESULTS</b>Overall survival time was (16.0 ± 1.4) months (x(-) ± s), overall 1- and 2-year survival rates were 56.4% and 26.5%, respectively. No patient survived over 5 years in these cases who had been diagnosed more than 5 years (except for those who lost). Univariate analysis showed that primary site, pathological grade, T-stage, N-stage and clinical stage were significant prognostic factors for the survival of the patients (P < 0.05). The survival rates of laryngeal carcinoma whether with tracheotomy were no statistically significant (P > 0.05). Multivariate analysis showed survival rates statistically correlated with T stage and N stage (hazard ratio were 1.812 and 1.557, P < 0.05).</p><p><b>CONCLUSIONS</b>The development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgical such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological grade, T-stage, N-stage and clinical stage, and of them, T-stage and N-stage are the independent prognostic factors.</p>

Clinical study on mometasone furoate nasal spray in the treatment of non-allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the outcome of mometasone furoate nasal spray (MFNS) used for 3 months on non-allergic rhinitis (NAR).</p><p><b>METHODS</b>In this multicenter study, NAR patients were enrolled from eight hospitals and received MFNS 200 microgram once daily for 3 months. The patients were followed-up for three times (at baseline, month 1 and month 3) to record the symptom scores and nasal endoscopic appearances. At the same time, the adverse events frequency was recorded and analyzed.</p><p><b>RESULTS</b>A total of 188 NAR cases were enrolled in the study. The total nasal symptom score assessment descended significantly at month 1 (1.70 ± 0.75) and month 3 (0.95 ± 0.79) visits versus at baseline (2.67 ± 0.68, Z value were from -11.603 to -10.491, all P < 0.01). The individual symptoms, including nasal stuffiness, nasal discharge, nasal stuffiness-related dizziness or headache, hyposmia, sleep quality, daily life activity, work or study efficiency, mental status, and whole body fatigue, also showed less scores at month 1 and month 3 visits versus at baseline (Z value were from -11.313 to -6.802, all P < 0.01). At the same time, nasal mucosal appearances assessed by endoscopy had lower scores at month 1 (1.40 ± 0.62) and month 3 (0.75 ± 0.71) visits versus at baseline (2.27 ± 0.73, Z value were from -11.484 to -10.002, all P < 0.01). Additionally, adverse events were only observed in 5.3% cases with light rhinorrhagia and nasal dryness. No other side effect was found.</p><p><b>CONCLUSIONS</b>A 3-months administration of intranasal mometasone can effectively and safely improve NAR patients' clinical symptom and nasal mucosal appearances.</p>

Effect of tumor necrosis factor-alpha on the permeability of strial capillary endothelial cells in guinea pig cochlea / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To perform an initial study on possible molecular regulatory mechanisms of TNF-alpha to the permeability of strial capillary endothelial cells in guinea pig cochlea</p><p><b>METHODS</b>Strial capillary endothelial cells in guinea pig cochlea was dissociated and cultured to establish a model for its permeability in vitro. The animals were divided into TNF-alpha, TNF-alpha + L-arginine (L-Arg), TNF-alpha + NG-monomethyl-L-arginine (L-NMMA) and control groups. In order to measure the alternations of permeation rate, Evans blue was used in different time by different concentrations to detect contents of F-actin in each group under immunofluorescence laser scanning confocal microscope.</p><p><b>RESULTS</b>TNF-alpha increased permeability of strial capillary endothelial cells notably, and permeation rate to Evans blue heightened significantly (P < 0.01) and increased under higher concentrations of TNF-alpha as well as lengthened the durations. Being as a NO donator, L-Arg significantly enhanced the ability of TNF-alpha which increasing permeability of strial capillary endothelial cells; permeation rate to Evans blue heightened significantly (P < 0.01), which obviously rose up when the concentration of Evans blue added. L-NMMA, NO inhibitor, was able to weaken the ability of TNF-alpha which increasing permeability of strial capillary endothelial cells; permeation rate to Evans blue decreased significantly (P < 0.01), which obviously fell down when the concentration of L-NMMA added. TNF-alpha decreased F-actin in strial capillary endothelial cells (P < 0.01), more TNF-alpha, less F-actin; L-Arg could be further the inhibition to F-actin content (P < 0.05); L-NMMA held back the trend (P < 0.05).</p><p><b>CONCLUSIONS</b>TNF-alpha can increase permeability of strial capillary endothelial cells of guinea pig cochlea. NO may be one of the important molecular regulators to permeability of strial capillary endothelial cells by TNF-alpha, and changes of F-actin content probably relate to the regulation in these cells.</p>

Adenoviral-mediated APE/Ref-1 expression protects rat spiral ganglion cells from oxidative damage / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To address the question if apurinic/apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) involved in preventing spiral ganglion cells oxidative damage after oxidative stress.</p><p><b>METHODS</b>Primary cultured rat spiral ganglion cells were infected with the adenovirus containing APE/Ref-1 for 48 h, then treated with H2O2 (0, 10, 25, 50, 100, 300 micromol/L) for 1 h, and finally changed back into normal medium. Western blot were used to detect the level of APE/Ref-1 protein in the infected cells to ensure APE/Ref-1 over expression as a result of adenovirus infection. The cell viability was determined by MTT and the apoptosis of spiral ganglion cells was determined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL).</p><p><b>RESULTS</b>Western blot showed that infection of adenovirus resulted in APE/Ref-1 over expression in the spiral ganglion cells. Over expression of APE/Ref-1 significantly improved cell viability in cultures treated with different concentration H2O2 from 50 to 300 micromol/L However, the apoptosis of cells was significantly inhibited.</p><p><b>CONCLUSIONS</b>Over expression of APE/Ref-1 could protect spiral ganglion cells from oxidative damage.</p>

Morphology effects of shear stress in cochlear microvascular endothelial cells in guinea pigs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To observe the effects of different shear stresses on the morphological changes in cochlear microvascular endothelial cells cultured in vitro so as to enrich the mechanism of the blood-labyrinth barrier.</p><p><b>METHODS</b>The morphological photos of cochlear microvascular endothelial monolayer cells were obtained with the hydrodynamic system design and the morphological parameters such as Pyx and Q were detected.</p><p><b>RESULTS</b>Through digestion with collagenase type I, the monolayer cells of cochlear microvascular endothelial monolayer were obtained. As to cochlear microvascular endothelial cells in guinea pigs, no morphological changes of the cells were found when shear stresses of 0. 0883 Pa acting for 24 h. When shear stress was 0.1184 Pa acting for 8 h, compliant changes from former disorderliness into orderliness happened following the direction of the flowing liquid of the cellular morphology. The changing tendency was in a time-dependent manner.</p><p><b>CONCLUSIONS</b>Cochlear microvascular endothelial cells in guinea pigs after the effect of shear stress are morphologically different from statically cultured endothelial cells. Range of the shear stress that cochlear microvascular endothelial cells can tolerate is little.</p>

Characteristics of hearing loss caused by local microcirculatory disorders in cochlea of guinea pigs / 第三军医大学学报

Objective　To study the characteristics of hearing loss caused by local microcirculatory disorders in the cochlea of guinea pigs. Methods　The local microcirculatory disorders in the cochlea basal turn near terminal or in the cupule of cochlea of guinea pigs were induced by photochemical reaction. The morphological changes in the cochlea were observed with light microscopy. The compound action potential N1 (CAPN1) amplitude, latency, threshold shift evoked by short tone burst were recorded by Madsen 2250 system. Results　When the local microcirculatory disorders took place in the cochlea basal turn near terminal, the hearing losses were more remarkable in the high-range frequencies, but with low-range ones to some extent. If the local microcirculatory disorders was induced in the cochlea cupule, the hearing losses were mainly in the low-range frequencies companying with some high-frequency ones. Conclusion　Local microcirculatory disorders in the different parts of the cochlea cause different types of hearing loss in different frequency.

Role of cochlea microvasculature permeability changes in guinea pigs after inner ear ischemia / 第三军医大学学报

Objective　To study the cochlea microvasculature permeability changes of the inner ear in guinea pigs, so as to clarify the possible role of the cochlea microvasculature permeability changes in the ischemic injury of inner ears. Methods　Modified method of Evans blue fluorescence was used to observe the changes of permeability of the cochlea microvasculature in the animal model of cochlea microcirculatory disorders which was caused by photochemical reaction. CAPN1 threshold was recorded by using Madsen 2 250 to study the hearing loss. Results　The amounts of Evens blue crossing the cochlea microvasculature were (1.709±0.769) and (2.849 ±0.653) μg/per animal 2 and 4 h after the development of cochlea microcirculatory disorder in guinea pigs, respectively (P<0.01); and their hearing loss were （24.44 ±7.27） and （38.33±7.91）dBpeSPL in 2 and 4 h, respectively (P<0.01)． Conclusion　The permeability of the cochlea microvasculature increases along with the duration of cochlea microcirculatory disorder occur and the increase of cochlea microvasculature permeability might be one of the important mechanisms inducing cochlear ischemic lesions.

Isolation, culture and characterization of cochlea microvascular endothelial cells from guinea pigs / 第三军医大学学报

Objective　To set up a reliable method for isolating and culturing cochlea microvascular endothelial cells. Methods　Cochlea stria was separated by micrergy from guinea pigs and the stria tissue nubbles were cultured in vitro. Results　Two days later, a few cells were seen disseminately around partial tissue nubbles and their number was increased with time prolongation. There were some cellular colonies consisted of large quantity of cells around the partial tissue nubbles on 10 th day. Under the inversion microscope, the single cultured cells presented a long fusiform and the confluent monolayer cells linked tightly and exhibited the typical structure of “scree” of cultured endothelial cells in vitro. After purification, over 95% of the cultured cells showed factorⅧ relative antigen positive reaction. Conclusion　The method used in this study can obtain cochlea microvascalar endothelial cells of guinea pig in vitro.

Characteristics of hearing loss caused by local microcirculatory disorders in cochlea of guinea pigs / 第三军医大学学报

Objective　To study the characteristics of hearing loss caused by local microcirculatory disorders in the cochlea of guinea pigs. Methods　The local microcirculatory disorders in the cochlea basal turn near terminal or in the cupule of cochlea of guinea pigs were induced by photochemical reaction. The morphological changes in the cochlea were observed with light microscopy. The compound action potential N1 (CAPN1) amplitude, latency, threshold shift evoked by short tone burst were recorded by Madsen 2250 system. Results　When the local microcirculatory disorders took place in the cochlea basal turn near terminal, the hearing losses were more remarkable in the high-range frequencies, but with low-range ones to some extent. If the local microcirculatory disorders was induced in the cochlea cupule, the hearing losses were mainly in the low-range frequencies companying with some high-frequency ones. Conclusion　Local microcirculatory disorders in the different parts of the cochlea cause different types of hearing loss in different frequency.

Role of cochlea microvasculature permeability changes in guinea pigs after inner ear ischemia / 第三军医大学学报

Objective　To study the cochlea microvasculature permeability changes of the inner ear in guinea pigs, so as to clarify the possible role of the cochlea microvasculature permeability changes in the ischemic injury of inner ears. Methods　Modified method of Evans blue fluorescence was used to observe the changes of permeability of the cochlea microvasculature in the animal model of cochlea microcirculatory disorders which was caused by photochemical reaction. CAPN1 threshold was recorded by using Madsen 2 250 to study the hearing loss. Results　The amounts of Evens blue crossing the cochlea microvasculature were (1.709±0.769) and (2.849 ±0.653) μg/per animal 2 and 4 h after the development of cochlea microcirculatory disorder in guinea pigs, respectively (P<0.01); and their hearing loss were （24.44 ±7.27） and （38.33±7.91）dBpeSPL in 2 and 4 h, respectively (P<0.01)． Conclusion　The permeability of the cochlea microvasculature increases along with the duration of cochlea microcirculatory disorder occur and the increase of cochlea microvasculature permeability might be one of the important mechanisms inducing cochlear ischemic lesions.

Isolation, culture and characterization of cochlea microvascular endothelial cells from guinea pigs / 第三军医大学学报

Objective　To set up a reliable method for isolating and culturing cochlea microvascular endothelial cells. Methods　Cochlea stria was separated by micrergy from guinea pigs and the stria tissue nubbles were cultured in vitro. Results　Two days later, a few cells were seen disseminately around partial tissue nubbles and their number was increased with time prolongation. There were some cellular colonies consisted of large quantity of cells around the partial tissue nubbles on 10 th day. Under the inversion microscope, the single cultured cells presented a long fusiform and the confluent monolayer cells linked tightly and exhibited the typical structure of “scree” of cultured endothelial cells in vitro. After purification, over 95% of the cultured cells showed factorⅧ relative antigen positive reaction. Conclusion　The method used in this study can obtain cochlea microvascalar endothelial cells of guinea pig in vitro.