Identification of miRNA expression profile in middle ear cholesteatoma using small RNA-sequencing.

BACKGROUND: The present study aims to identify the differential miRNA expression profile in middle ear cholesteatoma and explore their potential roles in its pathogenesis. METHODS: Cholesteatoma and matched normal retroauricular skin tissue samples were collected from patients diagnosed with acquired middle ear cholesteatoma. The miRNA expression profiling was performed using small RNA sequencing, which further validated by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs in cholesteatoma were predicted. The interaction network of 5 most significantly differentially expressed miRNAs was visualized using Cytoscape. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were processed to investigate the biological functions of miRNAs in cholesteatoma. RESULTS: The miRNA expression profile revealed 121 significantly differentially expressed miRNAs in cholesteatoma compared to normal skin tissues, with 56 upregulated and 65 downregulated. GO and KEGG pathway enrichment analyses suggested their significant roles in the pathogenesis of cholesteatoma. The interaction network of the the 2 most upregulated (hsa-miR-21-5p and hsa-miR-142-5p) and 3 most downregulated (hsa-miR-508-3p, hsa-miR-509-3p and hsa-miR-211-5p) miRNAs identified TGFBR2, MBNL1, and NFAT5 as potential key target genes in middle ear cholesteatoma. CONCLUSIONS: This study provides a comprehensive miRNA expression profile in middle ear cholesteatoma, which may aid in identifying therapeutic targets for its management.

Association between the atherogenic index of plasma and hearing loss based on a nationwide cross-sectional study.

BACKGROUND: Hearing loss (HL) is a worldwide public health issue for which the role of dyslipidemia has not been fully elucidated. This study aimed to use the atherogenic index of plasma (AIP), a well-established serum lipid marker, to investigate the association of dyslipidemia with HL among the general population. METHODS: Participants (n = 3267) from the National Health and Nutrition Examination Survey database (2005-2012, 2015-2018) were included in the present study. The AIP was calculated based on the following formula: log10 (triglycerides/high-density lipoprotein cholesterol). HL was defined as a pure-tone average of at least 20 dBHL in the better ear. Weighted multivariable logistic regression, subgroup analysis, generalized additive model, and threshold analysis were adopted to reveal the association between the AIP and HL. RESULTS: In this study of US adults, a positive association was found between the AIP and high-frequency HL. However, the association between the AIP and low-frequency HL was not as strong. In addition, a reverse L-shaped curve with an inflection point located at -0.27 was detected between the AIP and high-frequency HL, followed by a significant positive association after the inflection point. CONCLUSIONS: The potential of the AIP as a bioindicator for high-frequency HL is noteworthy, and maintaining an AIP value below a certain threshold might provide beneficial outcomes in the management of high-frequency HL.

Mesenchymal Stem Cell-Derived Exosomes Promote Recovery of The Facial Nerve Injury through Regulating Macrophage M1 and M2 Polarization by Targeting the P38 MAPK/NF-Κb Pathway.

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Prognostic Factors Affecting Hearing in Otitis Media With ANCA-Associated Vasculitis Patients: A Systematic Review and Meta-Analysis.

Objectives: To conduct a systematic review and meta-analysis of clinical studies describing the possible prognostic factors affecting hearing outcomes in Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) patients. To provide guidance for clinical work, avoiding profound irreversible hearing loss affecting patients' lives. Methods: A literature search was performed in PubMed, MEDLINE, EMBASE, Cochrane, Scopus, and Web of Science to identify English articles published before December 1, 2022. After screening the articles, the Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the extracted literature, and studies with high quality (score > 6) were included. Results: Four studies were included: 1 was a retrospective cohort study, and 3 were case-control studies. We performed a meta-analysis of 4 factors: facial palsy, hypertrophic pachymeningitis, ANCA-negative status, and the period from onset to diagnosis. The results showed that there was a significant association between facial palsy [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.07-2.15; I2 = 0%; P = .02], hypertrophic pachymeningitis (OR 1.73; 95% CI 1.18-2.53; I2 = 24%; P = .005), ANCA negativity (OR 1.75; 95% CI 1.11-2.77; I2 = 33; P = .02), and poor hearing prognosis in OMAAV patients. However, the period from onset to diagnosis (SEM ± SD 2.54; 95% CI -1.56 to 6.64; I2 = 98%; P = .22) of OMAAV was not significantly associated with poor hearing outcomes. Conclusion: We found that OMAAV patients with facial palsy, hypertrophic pachymeningitis, and ANCA negativity have a significant association with poor hearing prognosis, which provides diagnosis and treatment guidance in protecting patients' hearing.

Gracillin relieves pulmonary fibrosis by suppressing the STAT3 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components of Dioscorea quinqueloba which has been used in herbal medicines for treating some inflammatory diseases. Therefore, it may be a potential drug candidate for PF management. AIM OF THE STUDY: This study aims to elucidate and verify the anti-pulmonary fibrosis effect of gracillin. METHODS: We established an in vivo model of PF by treatment of mice with bleomycin (BLM) and an in vitro model by treatment of NIH-3T3 cells with TGF-ß1. Pathological changes to the structure of lung tissue, pulmonary function, inflammatory exudation of bronchoalveolar lavage fluid (BALF) and deposition of collagen were detected in vivo, and extracellular matrix (ECM) deposition and migration were evaluated in vitro. The significance of gracillin on STAT3 phosphorylation and nuclear translocation were evaluated by western blotting, immunohistochemistry and immunofluorescence assays. The STAT3 transcriptional activity was quantified with a dual-luciferase reporter assay. Recovery experiments were performed by plasmid-directed overexpression of STAT3. RESULTS: We found that gracillin could improve pulmonary function, reduce lung inflammation and mitigate collagen deposition to ameliorate BLM-induced PF in mice. Gracillin also suppressed TGF-ß1-induced increases in ECM deposition biomarkers, including COL1A1, fibronectin, α-SMA, N-cad and vimentin, and repressed migration in NIH-3T3 cells. Additionally, gracillin suppressed the phosphorylation, nuclear translocation and transcriptional action of STAT3. Furthermore, the decreased ECM deposition and migration upon gracillin treatment were abrogated upon overexpression of STAT3 in NIH-3T3 cells. CONCLUSIONS: Gracillin protects against PF by inhibiting the STAT3 axis, providing a safe and efficacious approach to treating PF.

The dynamic cellular landscape of grafts with acute rejection after heart transplantation.

BACKGROUND: Acute cellular rejection (ACR) is a major barrier to the long-term survival of cardiac allografts. Although immune cells are well known to play critical roles in ACR, the dynamic cellular landscape of allografts with ACR remains obscure. METHODS: Single-cell RNA sequencing (scRNA-seq) was carried out for mouse cardiac allografts with ACR. Bioinformatic analysis was performed, and subsequent transplant experiments were conducted to validate the findings. RESULTS: Despite an overall large depletion of cardiac fibroblasts (CFBs), highly expanded cytotoxic T lymphocytes and a CXCL10+Gbp2+ subcluster of CFBs were enriched within grafts at the late stage. CXCL10+Gbp2+ CFBs featured strong interferon responsiveness and high expression of chemokines and major histocompatibility complex molecules, implying their involvement in the recruitment and activation of immune cells. Cell‒cell communication analysis revealed that CXCL9/CXCL10-CXCR3 might contribute to regulating CXCL10+Gbp2+ CFB-induced chemotaxis and immune cell recruitment. In vivo transplant studies revealed the therapeutic potential of CXCR3 antagonism in transplant rejection. CONCLUSIONS: The findings of our study unveiled a novel CFB subcluster that might mediate acute cardiac rejection. Targeting CXCR3 could prolong allograft survival.

Mucus-Permeable Sonodynamic Therapy Mediated Amphotericin B-Loaded PEGylated PLGA Nanoparticles Enable Eradication of Candida albicans Biofilm.

Background: Candida albicans (C. albicans) forms pathogenic biofilms, and the dense mucus layer secreted by the epithelium is a major barrier to the traditional antibiotic treatment of mucosa-associated C. albicans infections. Herein, we report a novel anti-biofilm strategy of mucus-permeable sonodynamic therapy (mp-SDT) based on ultrasound (US)-mediated amphotericin B-loaded PEGylated PLGA nanoparticles (AmB-NPs) to overcome mucus barrier and enable the eradication of C. albicans biofilm. Methods: AmB-NPs were fabricated using ultrasonic double emulsion method, and their physicochemical and sonodynamic properties were determined. The mucus and biofilm permeability of US-mediated AmB-NPs were further investigated. Moreover, the anti-biofilm effect of US-mediated AmB-NPs treatment was thoroughly evaluated on mucus barrier abiotic biofilm, epithelium-associated biotic biofilm, and C. albicans-induced rabbit vaginal biofilms model. In addition, the ultrastructure and secreted cytokines of epithelial cells and the polarization of macrophages were analyzed to investigate the regulation of local cellular immune function by US-mediated AmB-NPs treatment. Results: Polymeric AmB-NPs display excellent sonodynamic performance with massive singlet oxygen (1O2) generation. US-mediated AmB-NPs could rapidly transport through mucus and promote permeability in biofilms, which exhibited excellent eradicating ability to C. albicans biofilms. Furthermore, in the vaginal epithelial cells (VECs)-associated C. albicans biofilm model, the mp-SDT scheme showed the strongest biofilm eradication effect, with up to 98% biofilm re-formation inhibition rate, improved the ultrastructural damage, promoted local immune defense enhancement of VECs, and regulated the polarization of macrophages to the M1 phenotype to enhance macrophage-associated antifungal immune responses. In addition, mp-SDT treatment exhibited excellent therapeutic efficacy against C. albicans-induced rabbit vaginitis, promoted the recovery of mucosal epithelial ultrastructure, and contributed to the reshaping of a healthier vaginal microbiome. Conclusion: The synergistic anti-biofilm strategies of mp-SDT effectively eradicated C. albicans biofilm and simultaneously regulated local antifungal immunity enhancement, which may provide a new approach to treat refractory drug-resistant biofilm-associated mucosal candidiasis.

Dihydroartemisinin Attenuates Hypoxic Pulmonary Hypertension via the Downregulation of miR-335 Targeting Vangl2.

Dihydroartemisinin (DHA) is a traditional antimalarial drug. DHA plays a crucial role in preventing pulmonary hypertension (PH); however, its regulatory function on microRNAs (miRNAs) in PH remains unclear. This study aimed to investigate whether DHA exerts its protective functions by regulating miR-335 in PH. Hypoxia-induced PH models were induced both in vitro and in vivo. Mice were treated with various concentrations of DHA, and pulmonary arterial smooth muscle cells (PASMCs) were treated with DHA, miR-335 inhibitor, miR-335 mimic, or Van Gogh-like 2 (Vangl2) plasmid. The expression of miR-335 and Vangl2, pulmonary arterial remodeling index; right ventricular hypertrophy index; and proliferation and migration indexes were measured. DHA improved pulmonary vascular remodeling and alleviated PH in vivo. miRNA sequencing and real-time PCR results further show that the increase in hypoxia-induced miR-335 was avoided by DHA administration, and miR-335 increased the hypoxia-induced PASMC proliferation and migration. MiRNA databases and dual-luciferase reporter assay show that miR-335 directly targets Vangl2, and Vangl2 decreased the hypoxia-induced PASMC proliferation and migration. The miR-335 inhibitor failed to inhibit hypoxia-induced proliferation and migration upregulation in Vangl2 knockdown PASMCs, and the effect of DHA can be blocked by miR-335 upregulation. In hypoxic PH, MiR-335 is increased, whereas Vangl2 is decreased. MiR-335 can significantly promote the hypoxia-induced proliferation and migration of PASMCs by targeting the Vangl2 gene. DHA effectively reverses the hypoxia-induced upregulation of miR-335 expression, avoiding the miR-335-mediated downregulation of Vangl2 and thereby promoting the expression of Vangl2 to prevent PH.

A Preliminary Study on the Relationship Between High-Resolution Computed Tomography and Pulmonary Function in People at Risk of Developing Chronic Obstructive Pulmonary Disease.

Objectives: Patients with chronic obstructive pulmonary disease (COPD) have high morbidity and mortality, the opportunity to carry out a thoracic high-resolution CT (HRCT) scan may increase the possibility to identify the group at risk of disease. The aim of our study was to explore the differences in HRCT emphysema parameters, air trapping parameters, and lung density parameters between high and low-risk patients of COPD and evaluate their correlation with pulmonary function parameters. Methods: In this retrospective, single-center cohort study, we enrolled outpatients from the Physical Examination Center and Respiratory Medicine of The First Affiliated Hospital of Wenzhou Medical University. The patients who were ≥ 40 years-old, had chronic cough or sputum production, and/or had exposure to risk factors for the disease and had not reached the diagnostic criteria is considered people at risk of COPD. They were divided into low-risk group and high-risk group according to FEV1/FVC ≥ 80% and 80%>FEV1/FVC ≥ 70%. Data on clinical characteristics, clinical symptom score, pulmonary function, and HRCT were recorded. Results: 72 COPD high-risk patients and 86 COPD low-risk patients were enrolled in the study, and the air trapping index of left, right, and bilateral lungs of the high-risk group were higher than those of the low-risk group. However, the result of mean expiratory lung density was opposite. The emphysema index of left, right, and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.22, -0.26). Consistently, the air trapping index of left and right lungs and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.23, -0.28). Additionally, the mean expiratory lung density of left and right lungs and bilateral lungs were positively correlated with FEV1/FVC (correlation coefficients were 0.31, 0.25, 0.29). Conclusion: The emphysema index, air trapping index and the mean expiratory lung density shows significantly positive correlation with FEV1/FVC which can be used to assess the pulmonary function status of people at risk of COPD and provide a useful supplement for the early and comprehensive assessment of the disease.

Acetylshikonin exerts anti-tumor effects on non-small cell lung cancer through dual inhibition of STAT3 and EGFR.

BACKGROUND: Lung cancer is one of the most common types of malignant tumor. It has one of the highest morbidity and mortality rates worldwide, and approximately 85% of cases are non-small cell lung cancer (NSCLC). Clinically, several EGFR inhibitors have been used to treat NSCLC, but resistance can develop. Studies have shown that cross talk between signal transducer and activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR) can mediate drug resistance. Acetylshikonin has obvious antitumor effects, but the mechanism of action is still unclear. PURPOSE: To analyze the antitumor activity of acetylshikonin in lung cancer and clarify its molecular mechanism. METHODS: Methyl thiazolyl tetrazolium (MTT), colony formation and 5-ethynyl-2'-deoxyuridine (EDU) assays were performed to examine the effects of acetylshikonin in inhibiting the proliferation of NSCLC cells (PC-9, H1975 and A549). Scratch wound and transwell assays were used to evaluate the migration and invasion of NSCLC cells. Flow cytometry was employed to determine whether acetylshikonin could induce apoptosis. Proteome sequencing was used to identify the targets of acetylshikonin. Immunofluorescence staining and western blotting were utilized to verify the inhibition of STAT3 and EGFR phosphorylation. A xenotransplantation model was established to evaluate the efficacy of acetylshikonin in nude mice. RESULTS: Our data demonstrated that acetylshikonin significantly decreased the survival rate of human NSCLC cells, increased the apoptotic rate and inhibited cell migration dose-dependently. Immunofluorescence staining and western blotting analyses revealed that acetylshikonin inhibited EGFR and STAT3 pathways. Acetylshikonin also inhibited tumor growth in a xenograft model better than inhibitors of EGFR and STAT3. CONCLUSION: Acetylshikonin has anti-cancer effects on NSCLC cells by inhibiting EGFR and STAT3, indicating that acetylshikonin may be a new antitumor drug to treat NSCLC.

Integrative Analyses of Genes Associated With Otologic Disorders in Turner Syndrome.

Background: Loss or partial loss of one X chromosome induces Turner syndrome (TS) in females, causing major medical concerns, including otologic disorders. However, the underlying genetic pathophysiology of otologic disorders in TS is mostly unclear. Methods: Ear-related genes of TS (TSEs) were identified by analyzing differentially expressed genes (DEGs) in two Gene Expression Omnibus (GEO)-derived expression profiles and ear-genes in the Comparative Toxicogenomic Database (CTD). Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) analyses; Gene Set Enrichment Analysis (GSEA); and Gene Set Variation Analysis (GSVA) were adopted to study biological functions. Moreover, hub genes within the TSEs were identified by assessing protein-protein interaction (PPI), gene-microRNA, and gene-transcription factor (TF) networks. Drug-Gene Interaction Database (DGIdb) analysis was performed to predict molecular drugs for TS. Furthermore, three machine-learning analysis outcomes were comprehensively compared to explore optimal biomarkers of otologic disorders in TS. Finally, immune cell infiltration was analyzed. Results: The TSEs included 30 significantly upregulated genes and 14 significantly downregulated genes. Enrichment analyses suggested that TSEs play crucial roles in inflammatory responses, phospholipid and glycerolipid metabolism, transcriptional processes, and epigenetic processes, such as histone acetylation, and their importance for inner ear development. Subsequently, we described three hub genes in the PPI network and confirmed their involvement in Wnt/ß-catenin signaling pathway and immune cell regulation and roles in maintaining normal auditory function. We also constructed gene-microRNA and gene-TF networks. A novel biomarker (SLC25A6) of the pathogenesis of otologic disorders in TS was identified by comprehensive comparisons of three machine-learning analyses with the best predictive performance. Potential therapeutic agents in TS were predicted using the DGIdb. Immune cell infiltration analysis showed that TSEs are related to immune-infiltrating cells. Conclusion: Overall, our findings have deepened the understanding of the pathophysiology of otologic disorders in TS and made contributions to present a promising biomarker and treatment targets for in-depth research.

Small activating RNA activation of ATOH1 promotes regeneration of human inner ear hair cells.

The loss of inner ear hair cells leads to irreversible acoustic injury in mammals, and regeneration of inner ear hair cells to restore hearing loss is challenging. ATOH1 is a key gene in the development and regeneration of hair cells. Small activating RNAs (saRNAs) can target a gene to specifically upregulate its expression. This study aimed to explore whether small activating RNAs could induce the differentiation of human adipose-derived mesenchymal stem cells into hair cell-like cells with a combination of growth factors in vitro and thus provide a new strategy for hair cell regeneration and the treatment of sensorineural hearing loss. Fifteen small activating RNAs targeting the human ATOH1 gene were designed and screened in 293 T and human adipose-derived mesenchymal stem cells, and 3 of these candidates were found to be capable of effectively and stably activating ATOH1 gene expression. The selected small activating RNAs were then transfected into hair cell progenitor cells, and hair cell markers were examined 10 days after transfection. After transfection of the selected small activating RNAs, the expression of the characteristic markers of inner ear hair cells, POU class 4 homeobox 3 (POU4F3) and myosin VIIA (MYO7A), was detected. Human adipose-derived mesenchymal stem cells have the potential to differentiate into human hair cell progenitor cells. In vitro, small activating RNAs were able to induce the differentiation of hair cell progenitor cells into hair cell-like cells. Therefore, RNA activation technology has the potential to provide a new strategy for the regeneration of hair cells.

Hypocrellin A exerts antitumor effects by inhibiting the FGFR1 signaling pathway in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer, which is the deadliest form of cancer worldwide. Recent studies have shown that genes in the fibroblast growth factor (FGF) family are highly mutated in lung cancer, and fibroblast growth factor receptor 1 (FGFR1) has been found to be involved in various cancers, including lung cancer, suggesting that FGFR1 is a valid therapeutic target. Hypocrellin A (HA), a molecule with multiple biological activities, has been shown to influence cancer growth, but the specific mechanisms of its antitumor action have not been fully explored. METHODS: MTT, colony formation, wound healing, transwell cell invasion and EdU cell proliferation assays were performed upon HA treatment of three NSCLC cell lines, H460, PC-9 and H1975. Hoechst 33258 staining and caspase 3 activity assays were carried out to investigate the impact of HA on apoptosis in these cells. Molecular docking and surface plasmon resonance were conducted to assess binding of HA to FGFR1. A mouse tumor model was used to detect the NSCLC-inhibitory ability of HA in vivo. RESULTS: Through in vitro assays, HA was shown to negatively impact cell viability, migration, invasion and promote apoptosis in three human NSCLC cell line models. HA was shown to bind to FGFR1 and to inhibit its autophosphorylation and the phosphorylation of downstream signaling molecules. Inhibition of tumor growth was also demonstrated in a mouse xenograft tumor model, and no toxic effects of HA treatment were observed. CONCLUSIONS: HA inhibits the activity of the FGFR1 and STAT3 signaling pathways. HA thus represents a potential new FGFR1-targeted treatment for NSCLC.

A Novel Cell Morphology Analyzer Application in Head and Neck Cancer.

PURPOSE: Rapid and accurate diagnosis of the pathological characteristics of head and neck cancer and tumor resection margins is important. The DiveScope cell morphology analyzer (DiveScope) is a new endomicroscope that can rapidly image living tissues and cells. In this study, we preliminarily examined the accuracy of the DiveScope for determining the malignancy of head and neck cancers and the positivity/negativity of tumor resection margins and determined the consistency between diagnostic results with the DiveScope and those of frozen section pathology to provide a foundation for further clinical trials in pathological diagnosis of head and neck cancers and tumor resection margins. METHODS: Head and neck cancer samples and resection margin samples were rapidly stained ex vivo before observation under the DiveScope cell morphology analyzer. Experienced pathologists distinguished the benignity and malignancy of the tumors based on images obtained by the DiveScope in a double-blind manner to validate the diagnostic performance of the analyzer. RESULTS: We found that the cell morphology, cell nucleus morphology, karyoplasmic ratio, and even the nucleolus could be clearly distinguished. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of benign and malignant head and neck cancer according to DiveScope results were 10.55 and 0.04, respectively. The PLR and NLR of the head and neck cancer resection margins according to the DiveScope were 19.01 and 0, respectively. CONCLUSION: The DiveScope showed high accuracy in determining the benignity and malignancy of head and neck cancer and the positivity/negativity of resection margins, and its results were highly consistent with those of intraoperative frozen section pathology tests.

Predictors of anatomical and functional outcomes following tympanoplasty: A retrospective study of 413 procedures.

OBJECTIVES: To identify the predictors of anatomical and functional outcomes following tympanoplasty. STUDY DESIGN: A retrospective cohort study. METHODS: Patients with chronic suppurative otitis media (CSOM) who underwent a tympanoplasty at Peking Union Medical College Hospital from January 1, 2015 to December 31, 2019 were retrospectively included. Outcome measures included graft success and postoperative pure tone audiometry air-bone gap (PTA-ABG) at last follow-up (≥6 months). PTA-ABG and MERI were calculated. Descriptive, univariable, and multivariable logistic regression analyses were conducted to evaluate the predictors of the graft and hearing outcomes. RESULTS: During the study, 385 patients (167 male, 218 female, median age 44 years) undergoing 413 procedures were studied. Out of this, 219 ears underwent tympanoplasty, 45 ears had tympanoplasty with canal wall up mastoidectomy, and 149 ears had tympanoplasty with canal wall down mastoidectomy. At the last follow-up, the overall graft success rate was 91.3% (377/413) and the overall hearing success rate was 40% (165/413). Multivariable analysis results showed that the obstructed aditus ad antrum (OR 2.67, 95%CI 1.13-6.30; P = .025) was an independent prognostic factor for graft failures. Moreover, the obstructed aditus ad antrum (OR 2.18, 95%CI 1.16-4.08; P = .015) and MERI >3 (OR 6.53, 95%CI 3.55-12.02; P < .001) were independent predictors of hearing failures (PTA-ABG > 20 dB). CONCLUSIONS: Aditus ad antrum patency was an independent predictor of both graft and hearing success among patients following tympanoplasty. MERI score greater than three was found to be a significant predictor of postoperative hearing and could serve as a useful tool for assisting clinicians in perioperative risk assessment. LEVEL OF EVIDENCE: 4.

Targeted deletion of Atoh8 results in severe hearing loss in mice.

Atoh8, also named Math6, is a bHLH gene reported to have important functions in the developing nervous system, pancreas and kidney. However, the expression pattern and function of Atoh8 in the inner ear are still unclear. To study the function of Atoh8 in the developing mouse inner ear, we performed targeted deletion of Atoh8 by intercrossing Atoh8lacZ/+ mice. We studied the expression pattern of Atoh8 in the inner ear and found interesting results that Atoh8-null (Atoh8lacZ/lacZ ) mice were viable but smaller than their littermates and they were severely hearing impaired, which was confirmed by hearing tests (ABR, DPOAE). We collected 129 viable newborns from 18 litters by crossing Atoh8lacZ/+ mice and found that the distributions of Atoh8lacZ/+ , Atoh8lacZ/lacZ and wild type were very close to their expected Mendelian ratio by χ2 testing. However, no remarkable morphological changes in cochleae in mutant mice were detected under plastic sectioning and electron microscopy. No remarkable differences in the expression of Myosin6, Prestin, TrkC, GAD65, Tuj1, or Calretinin were detected between the mutant mice and the control mice. These findings indicate that Atoh8 plays an important role in the development of normal hearing, while further studies are required to elucidate its exact function in hearing.

Mechanisms of hydrogen sulfide removal by ground granulated blast furnace slag amended soil.

Ground granulated blast furnace slag (GGBS) amended soil has been found able to remove gaseous hydrogen sulfide (H2S). However, how H2S is removed by GGBS amended soil and why GGBS amended soil can be regenerated to remove H2S are not fully understood. In this study, laboratory column tests together with chemical analysis were conducted to investigate and reveal the mechanisms of H2S removal process in GGBS amended soil. Sulfur products formed on the surface of soil particle and in pore water were quantified. The test results reveal that the reaction between H2S and GGBS amended soil was a combined process of oxidation and acid-base reaction. The principal mechanism to remove H2S in GGBS amended soil was through the formation of acid volatile sulfide (AVS), elemental sulfur and thiosulfate. Soil pH value decreased gradually during regeneration and reuse cycles. It is found that the AVS plays a significant role in H2S removal during regeneration and reuse cycles. Adding GGBS increased the production of AVS and at the same time suppressed the formation of elemental sulfur. This mechanism is found to be more prominent when the soil water content is higher, leading to increased removal capacity.

Are retailers compliant with zoning regulations that ban tobacco sales near schools in Changsha, China?

BACKGROUND: Tobacco retail sales are prohibited within 100 m of schools in many large cities in China. However, little is known about the enforcement of this zoning regulation. The objectives of this study were to estimate tobacco retailers' compliance with the regulation, examine the density of tobacco retail stores, describe the types of tobacco products sold in stores and how they are marketed, and determine if there are displays of warning messages in retail stores around schools and in neighbourhoods in Changsha, China. METHODS: Tobacco retail stores located within 200 m of 36 schools and 36 residential neighbourhoods were audited by trained students with a validated audit form. RESULTS: On average, there were about 3 tobacco retail stores within 100 m of the front entrance of schools. The density of the stores and the types of tobacco products sold in the stores were similar near schools and in neighbourhoods. Over one-fourth of the stores had exterior tobacco advertisements. Interior advertising was slightly less prevalent, and it was most prevalent among tobacco shops (62.5%). Tobacco displays that target children were pervasive, with about 83% of tobacco retail stores displaying cigarettes within 1 m of the floor and 59% displaying cigarettes within 0.3 m of toys and candy. About 40% of stores within 100 m of a school had a visible retail licence. Only 19.6% of the stores had a 'smoke-free' sign and 22.2% had a 'no sales to minors' sign. CONCLUSIONS: We observed low enforcement of the regulation that bans tobacco retail sales near schools and high prevalence of tobacco displays that target children in Changsha, China. Chinese officials should act to effectively enforce the regulation bans of tobacco sales near schools. In addition, regulations are urgently needed to limit tobacco marketing practices at the point of sale, especially those targeting youth.

[Association between use of antibacterial agents in the first year of life and childhood asthma: a Meta analysis].

OBJECTIVE: To evaluate the association between the use of antibacterial agents in the first years of life and childhood asthma. METHODS: The Chinese and English databases CNKI, Wanfang Data, VIP, PubMed, and EBSCO were searched for prospective cohort studies on the association between the use of antibacterial agents in the first years of life and childhood asthma. Stata12.0 software was used to analyze the association through a Meta analysis. RESULTS: The articles with a high quality score and adjusted effective values for factors for lower respiratory tract infection were pooled, and a total of 8 studies were included. The results of the Meta analysis showed that the use of antibacterial agents in the first years of life increased the risk of childhood asthma (OR=1.14, 95%CI: 1.10-1.17, P<0.05). Compared with the children who used antibacterial agents 0-1 times in the first years of life, those who used more than 4 times had an increased risk of asthma (OR=1.28, 95%CI: 1.19-1.38, P<0.05). High-risk children (at least one immediate family member had asthma) who used antibacterial agents had an increased risk of asthma (OR=1.47, 95%CI: 1.20-1.81, P<0.05). CONCLUSIONS: The use of antibacterial agents in the first years of life increases the risk of childhood asthma. High-risk children who use antibacterial agents have an increased risk of asthma. The increased frequency of use of antibacterial agents in the first years of life is associated with an increased risk of childhood asthma, but the detailed dose relationship needs further investigation.