Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6.

Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. Considering the anti-inflammatory and antioxidant properties of Dex, we applied in vivo rat model as well as in vitro cardiomyocyte models (embryonic rat cardiomyocytes H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial ischemia reperfusion (I/R) injury. Transcriptomic sequencing for gene expression in heart tissues from control rats and Dex-treated rats identified that genes related to fatty acid metabolism were significantly regulated by Dex. Among these genes, the elongation of long-chain fatty acids (ELOVL) family member 6 (Elovl6) was most increased upon Dex-treatment. By comparing the effects of Dex on both wild type and Elovl6-knockdown H9c2 cells and NRCMs under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, we found that Elovl6 knockdown attenuated the protection efficiency of Dex, which was supported by the cytotoxicity endpoints (cell viability and lactate dehydrogenase release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays a key role in the process, which was further confirmed using palmitate exposure in both cells, as well as in an in vivo rat model. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provides better understanding on the fatty acid metabolism underlying the beneficial effects of Dex.

Self-Enhancement of Perfluorinated Sulfonic Acid Proton Exchange Membrane with Its Own Nanofibers.

High-performance proton exchange membrane (PEM) is crucial for the proton exchange membrane fuel cell (PEMFC). Herein, a novel "self-enhanced" PEM is fabricated for the first time, which is composed of perfluorinated sulfonic acid (PFSA) resin and its own nanofibers as reinforcement. With this strategy, the interfacial compatibility issue of conventional fiber-reinforced membranes is fully addressed and up to 80 wt% loading of PFSA nanofibers can be incorporated. Furthermore, on account of chain orientation within the PFSA nanofiber, single fiber exhibits super-high conductivity of 1.45 S cm-1, leading to state-of-the-art proton conductivity (1.1 S cm-1) of the as-prepared "self-enhanced" PEM so far, which is an order of magnitude increase compared with the bulk PFSA membrane (0.29 S cm-1). It surpasses any commercial PEM including the popular GORE-SELECT and Nafion HP membranes and is the only PEM with conductivity at 100 S cm-1 level. In addition, the mechanical strength and swelling ratio of membranes are both substantially improved simultaneously. Based on the high-performance "self-enhanced" PEM, high peak power densities of up to 3.6 W cm-2 and 1.7 W cm-2 are achieved in H2-O2 and H2-Air fuel cells, respectively. This strategy can be applied in any polymeric electrolyte membrane.

Oxygen-carrying acid-responsive Cu/ZIF-8 for photodynamic antibacterial therapy against cariogenic Streptococcus mutans infection.

Caries as a result of acid demineralization is the most common oral microbial infectious disease. Due to the small and complex intraoral operating space, it is challenging to completely remove Streptococcus mutans (S. mutans) and other cariogenic bacteria. As an intelligent acid-responsive photosensitive nanomaterial, O2-Cu/ZIF-8@Ce6/ZIF-8@HA (OCZCH) was chosen to adapt to the anaerobic and acidic microenvironment for inactivating S. mutans. In this work, OCZCH not only exhibits a regular nanomorphology in SEM and TEM images but also shows intelligent acid responsiveness as evidenced by the release of Ce6 and oxygen. When excited by near-infrared light at 650 nm, Ce6 releases reactive oxygen species (ROS) that act synergistically with internal oxygen to significantly enhance the antimicrobial therapeutic effect of photodynamic therapy (PDT). In vitro antimicrobial experiments showed that OCZCH could achieve an impressive sterilization effect against S. mutans and biofilm. Notably, the acid-producing ability of the bacteria was also significantly inhibited. With its oxygen-carrying photosensitizing properties, excellent responsiveness to acidic environments, and antimicrobial capacity under anaerobic conditions, OCZCH is considered an innovative candidate for clinical application in treating dental caries.

An Intelligent Method for Predicting Pacific Oyster (Crassostrea gigas) Freshness Using Deep Learning Fused with Malondialdehyde and Total Sulfhydryl Groups Information.

To achieve a non-destructive and rapid detection of oyster freshness, an intelligent method using deep learning fused with malondialdehyde (MDA) and total sulfhydryl groups (SH) information was proposed. In this study, an "MDA-SH-storage days" polynomial fitting model and oyster meat image dataset were first built. AleNet-MDA and AlxNet-SH classification models were then constructed to automatically identify and classify four levels of oyster meat images with overall accuracies of 92.72% and 94.06%, respectively. Next, the outputs of the two models were used as the inputs to "MDA-SH-storage days" model, which ultimately succeeded in predicting the corresponding MDA content, SH content and storage day for an oyster image within 0.03 ms. Furthermore, the interpretability of the two models for oyster meat image were also investigated by feature visualization and strongest activations techniques. Thus, this study brings new thoughts on oyster freshness prediction from the perspective of computer vision and artificial intelligence.

Correlation between grading methods of the cochlear endolymphatic hydrops and hearing loss in meniere's disease using three-dimensional real inversion recovery sequences.

BACKGROUND: The grading of intracochlear endolymphatic hydrops (EH) in Meniere's disease (MD) varies and lacks uniformity. AIMS: To compare the grading consistency and correlation between different grade methods of intracochlear EH and hearing loss. MATERIALS AND METHODS: Thirty-one patients diagnosed with MD underwent gadolinium-enhanced magnetic resonance imaging. Two radiologists graded the cochlea EH according to M1, M2, M3, or M4. We analysed the grading consistency and correlation between the EH degrees and hearing loss. RESULTS: The weighted kappa coefficients for inter-observer and intra-observer agreements for grading using M1 were good, whereas those for M2, M3, and M4 are excellent (all p < 0.001). The cochlear EH degree based on M2 was correlated with the low-to-mid frequencies, high frequencies, full frequencies, and MD clinical stage (all p < 0.05). The degrees based on M1, M3, M4 were only relevant to some of the 4 items. CONCLUSIONS: The grading consistency of M2, M3, M4 is relatively higher than that of M1, and M2 shows the strongest correlation with hearing loss. SIGNIFICANCE: Our results provide a more accurate method for assessing the clinical severity of MD.

Dihydrophenazine-derived oligomers from industrial waste as sustainable superior cathode materials for rechargeable lithium-ion batteries.

Organic materials with the 5,10-dihydrophenazine motif are superior cathode materials for lithium-ion batteries. However, the difficult accessibility and low capacity of such cathodes materials are obstacles to their practical applications. Herein, two novel oligomers, termed poly(5-methyl-10-(2-methacryloxypropyl)-5,10-dihydrophenazine) (PMPPZ) and poly(5-methyl-10-(2-methacryloxyethyl)-5,10-dihydrophenazine) (PMEPZ), were effectively synthesized from an industrial waste phenazine. Both oligomers were exploited successfully as excellent cathode materials for sustainable lithium-ion batteries. PMPPZ and PMEPZ exhibited good electrochemical stability and high initial discharge specific capacities of 88 mA h g-1 and 152 mA h g-1, respectively. Furthermore, upon in situ composition with MWCNTs, a composite material, named PMEPZ-MWCNTs, was achieved with enhanced stability and superior specific discharge capacity with the active-site utilization rate of up to 99%. PMEPZ-MWCNTs delivers high initial discharge capacity of up to 303 mA h g-1 and even 252 mA h g-1 after 300 cycles. Both oligomers exhibit double-electron transfer mechanisms. This work affords an alternative approach to utilizing phenazine as a useful material, circumventing the emission of vast environment harmful gases.

"I Sometimes Pretended to Get Groceries": Restrictive Deterrence in Drug Dealing.

Despite steady progress in drug control work, drug-related crimes are ranked third in the total number of criminal cases in China. Based on in-depth interviews with 24 offenders who are now incarcerated for drug offenses, this paper examines the strategies employed by drug offenders to evade detection and mitigate their punishment for drug dealing. Their most frequently-used strategies focus on filtering out risky people, ensuring information asymmetry and knowing when to stop. Exploring how offenders adapt their behavior in response to punishment helps to further our understanding of crime commission and control.

Co-transduction of dual-adeno-associated virus vectors in the neonatal and adult mouse utricles.

Adeno-associated virus (AAV)-mediated gene transfer is an efficient method of gene over-expression in the vestibular end organs. However, AAV has limited usefulness for delivering a large gene, or multiple genes, due to its small packaging capacity (< 5 kb). Co-transduction of dual-AAV vectors can be used to increase the packaging capacity for gene delivery to various organs and tissues. However, its usefulness has not been well validated in the vestibular sensory epithelium. In the present study, we characterized the co-transduction of dual-AAV vectors in mouse utricles following inoculation of two AAV-serotype inner ear (AAV-ie) vectors via canalostomy. Firstly, co-transduction efficiencies were compared between dual-AAV-ie vectors using two different promoters: cytomegalovirus (CMV) and CMV early enhancer/chicken ß-actin (CAG). In the group of dual AAV-ie-CAG vectors, the co-transduction rates for striolar hair cells (HCs), extrastriolar HCs, striolar supporting cells (SCs), and extrastriolar SCs were 23.14 ± 2.25%, 27.05 ± 2.10%, 57.65 ± 7.21%, and 60.33 ± 5.69%, respectively. The co-transduction rates in the group of dual AAV-ie-CMV vectors were comparable to those in the dual AAV-ie-CAG group. Next, we examined the co-transduction of dual-AAV-ie-CAG vectors in the utricles of neonatal mice and damaged adult mice. In the neonatal mice, co-transduction rates were 52.88 ± 3.11% and 44.93 ± 2.06% in the striolar and extrastriolar HCs, respectively, which were significantly higher than those in adult mice. In the Pou4f3+/DTR mice, following diphtheria toxin administration, which eliminated most HCs and spared the SCs, the co-transduction rate of SCs was not significantly different to that of normal utricles. Transgene expression persisted for up to 3 months in the adult mice. Furthermore, sequential administration of two AAV-ie-CAG vectors at an interval of 1 week resulted in a higher co-transduction rate in HCs than concurrent delivery. The auditory brainstem responses and swim tests did not reveal any disruption of auditory or vestibular function after co-transduction with dual-AAV-ie vectors. In conclusion, dual-AAV-ie vectors allow efficient co-transduction in the vestibular sensory epithelium and facilitate the delivery of large or multiple genes for vestibular gene therapy.

GJB2 gene therapy and conditional deletion reveal developmental stage-dependent effects on inner ear structure and function.

Pathogenic variants in GJB2, the gene encoding connexin 26, are the most common cause of autosomal-recessive hereditary deafness. Despite this high prevalence, pathogenic mechanisms leading to GJB2-related deafness are not well understood, and cures are absent. Humans with GJB2-related deafness retain at least some auditory hair cells and neurons, and their deafness is usually stable. In contrast, mice with conditional loss of Gjb2 in supporting cells exhibit extensive loss of hair cells and neurons and rapidly progress to profound deafness, precluding the application of therapies that require intact cochlear cells. In an attempt to design a less severe Gjb2 animal model, we generated mice with inducible Sox10iCre ERT2 -mediated loss of Gjb2. Tamoxifen injection led to reduced connexin 26 expression and impaired function, but cochlear hair cells and neurons survived for 2 months, allowing phenotypic rescue attempts within this time. AAV-mediated gene transfer of GJB2 in mature mutant ears did not demonstrate threshold improvement and in some animals exacerbated hearing loss and resulted in hair cell loss. We conclude that Sox10iCre ERT2 ;Gjb2 flox/flox mice are valuable for studying the biology of connexin 26 in the cochlea. In particular, these mice may be useful for evaluating gene therapy vectors and development of therapies for GJB2-related deafness.

AAV8-mediated Atoh1 overexpression induces dose-dependent regeneration of vestibular hair cells in adult mice.

Vestibular hair cells (HCs) are mechanoreceptors for the detection of head movement. Vestibular HCs of adult mammals never completely regenerate after damage, resulting in vestibular dysfunction. Overexpression of Atoh1 is effective for inducing HC regeneration. However, method of clinical feasibility and improvement of regenerative extent are both in need. Here we used an adeno-associated virus (AAV) serotype 8 vector of two different titers to overexpress Atoh1 in the injured utricles of adult mice. One month after virus inoculation, abundant myosin VIIa-positive cells and immature stereocilia were observed. Quantitative analyses revealed that Atoh1 overexpression replenished vestibular HCs in a dose-dependent manner. Vectors of a higher titer increased the number of myosin VIIa-positive cells compared to those of lower titer. Moreover, only Atoh1 overexpression in the higher titer group enhanced stereocilium regeneration, which is an important step in the maturation of regenerated HCs. Although the current treatment failed to initiate functional recovery of the animals, our results prompt further improvements in the recovery of vestibular dysfunction by AAV.

Epithelial-Mesenchymal Transition Participates in the Formation of Vestibular Flat Epithelium.

The vestibular sensory epithelium of humans and mice may degenerate into a layer of flat cells, known as flat epithelium (FE), after a severe lesion. However, the pathogenesis of vestibular FE remains unclear. To determine whether the epithelial-mesenchymal transition (EMT) participates in the formation of vestibular FE, we used a well-established mouse model in which FE was induced in the utricle by an injection of streptomycin into the inner ear. The mesenchymal and epithelial cell markers and cell proliferation were examined using immunofluorescence staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The function of the EMT was assessed through transcriptome microarray analysis. The results demonstrated that mesenchymal cell markers (α-SMA, S100A4, vimentin, and Fn1) were upregulated in vestibular FE compared with the normal utricle. Robust cell proliferation, which was absent in the normal status, was observed in the formation of FE. Microarray analysis identified 1,227 upregulated and 962 downregulated genes in vestibular FE. Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) were highly associated with several EMT-related GO terms, such as cell adhesion, cell migration, and extracellular matrix. Pathway enrichment analysis revealed that DEGs were enriched in the EMT-related signaling pathways, including extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/Akt signaling pathway and cell adhesion molecule. Protein-protein interaction networks screened 20 hub genes, which were Akt, Casp3, Col1a1, Col1a2, Fn1, Hgf, Igf1,Il1b, Irs1, Itga2, Itga5, Jun, Mapk1, Myc, Nras, Pdgfrb, Tgfb1, Thbs1, Trp53, and Col2a1. Most of these genes are reportedly involved in the EMT process in various tissues. The mRNA expression level of hub genes was validated using qRT-PCR. In conclusion, the present study indicates that EMT plays a significant role in the formation of vestibular FE and provides an overview of transcriptome characteristics in vestibular FE.

Suggestion of a Modified Classification for Congenital Middle Ear Cholesteatoma: Based on the Clinical Characteristics and Staging of Fifty-Seven Patients.

Objective: To explore more refined classification methods of congenital middle ear cholesteatoma (CMEC) based on two existing staging systems. Subjects and Methods: This study involved a retrospective data review of 57 patients (61 ears involved) with CMEC requiring the surgical treatment. Patients were classified into different stages according to Nelson, Potsic, and Modified Nelson staging system. Preoperative data and intraoperative findings were recorded. Results: The mean age at operation was 15 ± 15.04 years with a median of 10 years. The main clinical manifestation was hearing loss (72.13%). CMEC mass was mainly located in the posterior portion of the tympanic cavity (65.57%). No patient was classified into Potsic stage II. The erosion of incus happened in all cases. Patients with Nelson type 2 and type 3 had erosions to the structures out of middle ear, such as dura mater, lateral semicircle canal, and facial canal. Postoperative follow-up time was more than 24 months. Recurrence occurred in four patients (6.56%), all of them in Nelson type 2, who had received canal wall down mastoidectomy (three cases) and canal wall up mastoidectomy (one case). Conclusions: Nelson staging system was more suitable for advanced CMEC patients than Potsic staging system. The rare case of Potsic stage II restricted the application of Potsic staging system. Moreover, since both of two staging systems do not distinguish the type of involved ossicles, the authors recommended to subdivide Nelson type 2 into type 2a and type 2b based on the erosion of the ossicular chain, as well as subdivide Nelson type 3 into type 3a and 3b based on the erosion of structures out of middle ear, which was named as Modified Nelson staging system.

Identification of functional mutations at FOXP3 binding site within BIC gene that alter the expression of miR-155 in pigs.

MiR-155 is an immune microRNA encoded within the BIC gene. Dozens of researches have uncovered the importance of high expression of miR-155 in promoting the development of immune organs and strengthening immune response and inflammatory response. Some natural mutations located in the miR-155/BIC region were revealed to disturb the expression level of miR-155 in several mammalian species, and our previous study also identified several mutations occurring near the miR-155/BIC region in pigs. However, the consequences of BIC locus-harbored mutations in pig genome remain unclear. In this study, we used Chinese Meishan and British Large White pigs to identify mutations within the miR-155/BIC region, and explore whether there are effects on expressions of miR-155 and its target genes. Target sequencing identified six potential FOXP3 protein binding sites (AAACA) in the BIC gene, among which there were two A/C mutations (AAACC) at the -108 bp and -305 bp upstream of the miR-155 precursors in Meishan pigs, but not in Large White pigs. A series of experiments confirmed that the FOXP3 protein mainly binds to the -305 bp position, and the binding efficiency of the CC haplotype to FOXP3 protein was higher than that of the wild type, resulting in increased expression of miR-155, and consequentially decreased the expressions of its target genes. Our newly identified mutations are functional, which explain partial reasons for the difference in immunity between Meishan and Large White pigs, and provide potential molecular markers to genetically improve the disease resistance in the pig breeding practice.

Cellular origin and response of flat epithelium in the vestibular end organs of mice to Atoh1 overexpression.

A flat epithelium (FE) may be found in the vestibular end organs of humans and mice with vestibular dysfunction. However, the pathogenesis of FE is unclear and inducing hair cell (HC) regeneration is challenging, as both HCs and supporting cells (SCs) in vestibular FE are damaged. To determine the cellular origin of vestibular FE and examine its response to Atoh1 overexpression, we fate-mapped vestibular epithelial cells in three transgenic mouse lines (vGlut3-iCreERT2:Rosa26tdTomato, GLAST-CreERT2:Rosa26tdTomato, and Plp-CreERT2:Rosa26tdTomato) after inducing a lesion by administering a high dose of streptomycin. Atoh1 overexpression in vestibular FE was mediated by an adeno-associated virus serotype 8 (AAV8) vector. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, was administered with AAV8 to enhance Atoh1 overexpression. The transduction efficiency and population of myosin VIIa-positive cells were analyzed. A small number of HCs were present in vestibular FE. FE did not show broad GLAST-Cre or Plp-Cre expression, unlike the original SCs. SAHA dramatically enhanced AAV8-mediated exogenous gene overexpression, and Atoh1 overexpression plus SAHA promoted myosin VIIa expression in FE cells. Our data provide insight into FE formation and will facilitate studies of gene therapy for vestibular FE.

Canalostomy As a Surgical Approach to Local Drug Delivery into the Inner Ears of Adult and Neonatal Mice.

Local delivery of therapeutic drugs into the inner ear is a promising therapy for inner ear diseases. Injection through semicircular canals (canalostomy) has been shown to be a useful approach to local drug delivery into the inner ear. The goal of this article is to describe, in detail, the surgical techniques involved in canalostomy in both adult and neonatal mice. As indicated by fast-green dye and adeno-associated virus serotype 8 with the green fluorescent protein gene, the canalostomy facilitated broad distribution of injected reagents in the cochlea and vestibular end-organs with minimal damage to hearing and vestibular function. The surgery was successfully implemented in both adult and neonatal mice; indeed, multiple surgeries could be performed if required. In conclusion, canalostomy is an effective and safe approach to drug delivery into the inner ears of adult and neonatal mice and may be used to treat human inner ear diseases in the future.

The histone deacetylase inhibitor sodium butyrate protects against noise-induced hearing loss in Guinea pigs.

Noise-induced hearing loss (NIHL) severely impacts the quality of life of affected individuals. Oxidative stress resulting from noise exposure is a significant cause of NIHL. Although histone deacetylase (HDAC) inhibitors were shown to protect against NIHL, the underlying mechanism remains unclear, and it is not known how they act on noise-induced oxidative stress. In the current study, we investigated the expression levels of acetyl-histone H3 (Lys9) (H3-AcK9), histone deacetylase 1 (HDAC1), and 3-nitrotyrosine (3-NT), an oxidative stress marker, in a guinea pig model of NIHL using immunohistology and Western blotting. We then assessed the effects of systemic administration of the HDAC inhibitor, sodium butyrate (SB), on noise-induced permanent threshold shifts (PTS), hair cell (HC) loss, and changes in the above mentioned markers. The results showed that SB attenuated noise-induced PTS and outer hair cell loss. SB treatment promoted H3-AcK9 expression and repressed HDAC1 expression in the nuclei of HCs and Hensen's cells after noise exposure. Furthermore, SB attenuated the noise-induced increase of 3-NT expression in HCs and Hensen's cells. These findings suggest that SB protects against NIHL by reversing the noise-induced histone acetylation imbalance and inhibiting oxidative stress in cochlear HCs and Hensen's cells. SB treatment may represent a potential strategy to prevent and treat NIHL.

Cochleovestibular gene transfer in neonatal mice by canalostomy.

Impairments of the inner ear result in sensorineural hearing loss and vestibular dysfunction in humans. A large proportion of these disorders are congenital, and involve both auditory and vestibular systems. Therefore, genetic interventions to correct deficits must be administered during early developmental stages. In this study, we evaluated inner ear gene transfer in neonatal mice by canalostomy using an adeno-associated virus serotype 8 (AAV8) vector. AAV8 with the green fluorescence protein (GFP) gene was inoculated into the inner ear of the neonatal mice through the posterior semicircular canal (canalostomy). At 30 days following surgery, animals were subjected to swim tests and auditory brainstem response measurements. Then, the animals were euthanized and temporal bones were harvested for whole-mount preparation. GFP expression and morphological changes in the inner ear were assessed by immunohistochemistry. After surgery, no signs of vestibular dysfunction were found, and there were no significant differences in the auditory brainstem response threshold between AAV8-inoculated ears and nonsurgery ears. In the surgery ears, extensive GFP expression and no morphological lesions were detected in the cochlear and vestibular end organs. Robust GFP expression was found in inner hair cells, marginal cells, vestibular hair cells, and vestibular supporting cells. In conclusion, AAV8 inoculation through canalostomy into the inner ears of neonatal mice led to extensive overexpression of exogenous genes in the inner ear without affecting hearing or vestibular function. It serves as a promising approach for gene therapy of congenital cochleovestibular diseases.

E2F1-CDK1 pathway activation in kanamycin-induced spiral ganglion cell apoptosis and the protective effect of CR8.

Cochlear hair cell loss results in the secondary loss of spiral ganglion cells (SGCs). The death of these SGCs is due to apoptosis. The E2F1-cyclin dependent kinase 1 (CDK1) pathway is believed to represent an important mechanism of neuronal cell death. However, the role of this pathway in spiral ganglion neuronal apoptosis has not yet been reported. In this study, we deafened guinea pigs with a subcutaneous injection of kanamycin followed by an intravenous infusion of furosemide and then assayed the expression levels of cleaved caspase-3, E2F1, CDK1 and cleaved caspase-9 during the induced SGC apoptosis. Our results revealed that co-administration of kanamycin and furosemide rapidly induced hair cell loss in the guinea pigs and then resulted in a progressive loss of SGCs. Expression levels of E2F1 and CDK1 were obviously up-regulated at 1 and 3 days after deafening. Cleaved caspase-9 also increased robustly 1 or 2 weeks after the deafening procedure. The up-regulation of E2F1, CDK1 and cleaved caspase-9 was significantly attenuated by the systemic injection of CR8 (1mg/kg/day, intraperitoneally) starting at 5min after deafening. These findings indicate that the activation of the E2F1-CDK1 pathway and cell cycle re-entry contributes to the apoptosis of SGCs and that the selective inhibition of this signaling cascade may represent an attractive therapeutic strategy. CR8 has the potential to protect SGCs from apoptosis.

Tumor Necrosis Factor-α-Induced Ototoxicity in Mouse Cochlear Organotypic Culture.

Tumor necrosis factor (TNF)-α is a cytokine involved in acute inflammatory phase reactions, and is the primary upstream mediator in the cochlear inflammatory response. Treatment of the organ of Corti with TNF-α can induce hair cell damage. However, the resulting morphological changes have not been systematically examined. In the present study, cochlear organotypic cultures from neonatal mice were treated with various concentrations and durations of TNF-α to induce inflammatory responses. Confocal microscopy was used to evaluate the condition of hair cells and supporting cells following immunohistochemical staining. In addition, the ultrastructure of the stereocilia bundle, hair cells, and supporting cells were examined by scanning and transmission electron microscopy. TNF-α treatment resulted in a fusion and loss of stereocilia bundles in hair cells, swelling of mitochondria, and vacuolation and degranulation of the endoplasmic reticulum. Disruption of tight junctions between hair cells and supporting cells was also observed at high concentrations. Hair cell loss was preceded by apoptosis of Deiters' and pillar cells. Taken together, these findings detail the morphological changes in the organ of Corti after TNF-α treatment, and provide an in vitro model of inflammatory-induced ototoxicity.

A review of prophylactic antibiotics use in plastic surgery in China and a systematic review.

The purpose of this study was to investigate the use of antibiotic prophylaxis for plastic surgical procedures at our hospital, and to perform a systematic literature review of randomized controlled trials evaluating the use of prophylactic antibiotics in plastic surgery. The records of patients who received plastic surgical procedures with Class I surgical incisions between 2009 and 2010 were retrospectively reviewed. A systematic literature review was conducted for studies examining the use of prophylactic antibiotics for Class I surgical wounds. A total of 13,997 cases with Class I surgical incisions were included. Prophylactic antibiotics were given in 13,865 cases (99.1%). The antibiotics used were primarily cefuroxime, clindamycin, metronidazole, cefoxitin sodium, and gentamicin. The average duration of administration was 4.84 ± 3.07 (range, 1-51) days. Antibiotics were administered postoperatively in >99% of cases while preoperative antibiotic administration was only given in 32 cases (0.23%). Wound infections occurred in 21 cases for an overall infection rate of 0.15%. Fourteen studies met the inclusion criteria of the systematic review. There was marked variation in the timing of antibiotic administration with antibiotics given pre-, peri-, and postoperatively. Of studies that compared the use of prophylactic antibiotics with placebo, a reduction in wound infections was noted in 4 trials and no difference was noted in 6 trials. No significant difference in infection rates was shown between the prophylactic and postoperative arms. In conclusion, prophylactic antibiotics are overused in plastic surgical procedures. Evidence-based guidelines for the use of prophylactic antibiotics in plastic surgical procedures are needed.