Three-dimensional finite element analysis on cochlear implantation electrode insertion.

Studying the insertion process of cochlear implant (CI) electrode array (EA) is important to ensure successful, sufficient, and safe implantation. A three-dimensional finite element (FE) model was developed to simulate the insertion process. The cochlear structures were reconstructed from an average statistical shape model (SSM) of human cochlea. The electrode is simplified as a long and tapered beam of homogeneous elastic materials, contacting and interacting with the stiff cochlear structures. A quasi-static insertion simulation was conducted, the insertion force and the contact pressure between the electrode and the cochlear wall, were calculated to evaluate the smoothness of insertion and the risk of potential cochlear trauma. Based on this model, different EA designs were analyzed, including the Young's modulus, the straight or bended shape, the normal or a more tapped section size. The influence of the insertion angle was also discussed. Our simulations indicate that reducing the EA Young's modulus, tapering and pre-bending are effective ways to ensure safe and successful EA implantation. This model is beneficial for optimizing EA designs and is potentially useful for designing patient-specific CI surgery.

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs.

Background: Endolymphatic hydrops (EH) is considered as the pathological correlate of Menière's disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials. Objective: This study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models. Methods: In this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells. Results: The RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL). Conclusion: Endolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

Bioinformatics analysis of the complete sequences of cytochrome b of Takydromus sylvaticus and modeling the tertiary structure of encoded protein.

Cytochrome b (cyt b) gene complete sequences (1143bp) of Takydromus sylvaticus were sequenced. In order to clarify the phylogenetic position of the Takydromus sylvaticus, we investigated the phylogeny of 15 Takydromus spp. distributed in East-Asia by Maximum Parsimony (MP), Bayesian Inference (BI), and Maximum Likelihood (ML) methods using DNA fragments of cyt b genes. The results supported that the Platyplacopus merged into Takydromus and negated the validity of Platyplacopus. Furthermore, the prediction of tertiary structures of cyt b exhibited the CD loop region contain two short helices forming a hairpin arrangement, namely cd1 and cd2. Thermostability analysis shows that the CD-loop region is unstable thermodynamically and may provide mobility to amino acids located at the heme, and might provide high flexibility to the top of ISP (iron-sulfur protein) and the cavity region of Qo binding site. It suggested that the two short helices of CD loop region of cyt b was a dominating portion for ISP binding site.

Analysis of SOX4 gene mutation in non-small cell lung cancer tissues.

OBJECTIVE: To investigate the mutation of SOX4 gene in the different tumor tissues with pathological stages and types of non-small cell lung cancer (NSCLC), and to explore its roles in the progression of lung carcinoma. METHODS: The SOX4 gene HMG-box of lung cancer tissues and paracancerous tissues were amplified by PCR, 20 cases shown difference by single strand conformation polymorphyism analysis were sequenced. The DNA sequences were compared with normal sequences by software Clustal and DNAStar. RESULTS: In the 90 NSCLCs, 18 cases were found with mutations of SOX4 gene and were sequenced, and there were 2 mutational points. Seven were detected from squamous cell carcinoma, five from adenocarcinoma and six from adeno-squamous. Three were obtained from tissues in stage I, five in stage II, six in stage III, and four in stage IV. The mutation rate in stage II, III and IV was significantly higher than that in stage I. CONCLUSION: SOX4 gene mutation is not associated with pathology histological types of tumor, but it is significantly associated with pathological stages and the mutation rate increases gradually, which has relation with advanced pathological stages in NSCLC. The results indicate that the SOX4 gene mutations might be related in the lung carcinogenesis and tumor metastasis. The study also provides molecular data for study the links between the mutation of SOX gene and human oncogenesis.

Cloning, expression and bioactivity of duck BAFF.

B cell activating factor (BAFF) belonging to the TNF family is critical for B cell survival and maturation. In the present study, we identified a duck BAFF cDNA, named dBAFF, by RT-PCR and RACE strategies. The open reading frame (ORF) of this cDNA encodes a 288-amino acid protein containing a predicted transmembrane domain and a putative furin protease cleavage site like chicken BAFF (cBAFF), human BAFF (hBAFF) and mouse BAFF (mBAFF). The amino acid identity between biologically soluble dBAFF and cBAFF, hBAFF or mBAFF is 97, 78 and 71%, respectively. RT-PCR analysis showed the dBAFF gene is strongly expressed in the bursa of fabricius. Recombinant soluble dBAFF (dsBAFF) fused with NusA.tag was efficiently produced in Origami B (DE3) pLysS expression host strain. In vitro, purified dsBAFF was not only able to promote survival of bursa B cells, but also able to co-stimulate proliferation of mammalian B cells with anti-IgM. Furthermore, recombinant hsBAFF has a positive effect on duck bursa B cells survival. These findings indicate dBAFF plays an important role in survival and proliferation of duck B cells and because of its high conservation in the evolution, functional cross-reactivity exists between mammalian and duck BAFF.

[Study on relationship between HBV post-transcriptional regulatory element and response to IFN-alpha by using a reporter gene luciferase].

AIM: To identify the function of HBV post-transcriptional regulatory element(HPRE) in response to IFN-alpha by using the reporter gene luciferase (LUC). METHODS: The gene encoding LUC was obtained by PCR from the vector pGEM-luc and then cloned into the eukaryotic expression vector pcDNA3.0. The HPRE, HPREalphabeta(1) and HPREbeta(1)beta(2) fragments were amplified by PCR from HBV genome and then cloned into the recombinant vector pcDNA3.0-luc. These constructed plasmids were transfected into the human hepatoma cell line HepG2. The expression of LUC before and after the addition of IFN-alpha was detected by LUC assay system. RESULTS: The DNA sequencing analysis showed that the recombinant plasmids pcDNA3.0-luc, pcDNA3.0-luc-HPRE, pcDNA3.0-luc-HP-REalphabeta(1) and pcDNA3.0-luc-HPREbeta(1)beta(2) were successfully constructed. The results of LUC detection assay showed that HPRE, HPREalphabeta(1) and HPREbeta(1)beta(2) could enhance the expression of LUC before the addition of IFN-alpha. When IFN-alpha was added, only the fragment of HPRE, HPREbeta(1)beta(2) could significantly reduce the expression of LUC, but the expression of LUC was not influenced by HPREalphabeta(1). CONCLUSION: The functional element beta(2) of HPRE plays a more important part in response to IFN-alpha than the element alpha and beta(1), which may be valuable for further research on mechanisms of IFN-alpha therapy in HBV infection and function of HPRE binding protein.