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Objectives: Handheld otoscopy is the standard tool used to teach ear examination in undergraduate and postgraduate medical education. Previous studies have shown that the undergraduate teaching of ear examination with handheld otoscopes is inadequate, resulting in low self-reported levels of student confidence in their diagnostic skills. With the increase in popularity of endoscopic ear surgery, an increasing number of otolaryngologists are using endoscopes for office examinations of the ear due to the method’s superior visualization and excellent image qualities. However, medical students usually do not receive exposure to endoscopic ear examination during their undergraduate curriculum. The aim of this study is to assess our preliminary experience with teaching endoscopic ear examination to undergraduate medical students.Methods: A two-hour-long pilot practical course on basic ear examination was administered to undergraduate medical students with little to no previous experience with ear examination. The course was designed to minimize the duration of campus attendance and patient contact during the COVID-19 pandemic. The course included theoretical didactics, exemplary digital endoscopic images and peer physical practice of ear examination with both a handheld otoscope and a 0-degree endoscope. At the end of the course, the students completed a survey questionnaire consisting of eight questions mainly relating to their subjective confidence level with ear examination using either handheld otoscopes or endoscopes and their overall preference for either examination tool.Results: Most students expressed a preference for ear examination with endoscopes over that with handheld otoscopes and reported an improved confidence level in their diagnostic ability with the former technique. The vast majority of students supported the teaching of endoscopic ear examination to future medical students.Conclusion: The findings of this pilot project report and survey study support the early exposure of novice medical learners to endoscopic ear examination, which may help improve the confidence and diagnostic skill of medical students with regard to ear examination. The findings may have implications for the undergraduate teaching of ear examination in the post-COVID-19 era.

Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) -based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tail docking is widely used to control tail biting in pigs, but it is a painful and stressful procedure. The impact of non-docking trials on tail damage (TD) and ear lesions (EL) from weaning to slaughter was assessed on four commercial farms., Methods: A total of 898 docked pigs (396 DP) or undocked pigs (502 UP) were assessed for tail damage and ear lesions at the beginning and end of the weaner stage, during fattening and at the abattoir during slaughter., Results: The percentage of UP with shortened tails increased significantly from weaning to fattening, but the percentage of non-inflamed tails and tails without fresh lesions increased. In terms of severity of lesion, a lower percentage of pigs scored as 'no visible lesion' at the end of weaning compared to fattening, both for UP and DP (p < 0.05). DP always had a lower percentage of TD, whereas UP had a lower percentage of EL at the end of weaning., Limitation: It was not possible to statistically compare different preventive strategies trialed on farms as alternatives to docking., Conclusion: This study highlights that combining tail length and lesion score at slaughter could be a reliable on-farm welfare indicator., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Fucoidan from Saccharina japonica (SJF) was isolated and characterized, and its anti-inflammatory effects on fine dust/ambient particulate matter (PM)-stimulated HaCaT keratinocytes were investigated. SJF increased cell viability by reducing intracellular ROS production in PM-stimulated HaCaT keratinocytes. Moreover, SJF downregulated the expression/production of inflammatory cytokines (IL-6, IL-8, IL-13, IL-25, IL-33, TNF-α, IFN-γ, and TSLP) and chemokines (MDC and TARC) through modulating NF-κB/MAPK signaling in PM-stimulated HaCaT keratinocytes. Extended studies investigated the impact of SJF-treated HaCaT keratinocyte culture media on HDFs. Interestingly, media from SJF-treated HaCaT keratinocytes on HDFs demonstrated a notable downregulation of the production of inflammatory mediators such as TSLP, IL-6, IL-8, IL-13, and TNF-α, as well as TARC and MDC. Furthermore, the study examined the impact of SJF on 12-O-tetradecanoylphorbol 13-acetate (TPA) induced ear edema in BALB/c mice and results indicated the reduced ear thickness and decreased iNOS and COX-2 expression. Our study confirmed the effectiveness of SJF in ameliorating PM-induced skin inflammation in in vitro experiments, along with the TPA-induced in vivo inflammatory model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Current strategies for hypertrophic scar prevention and treatment are limited., Objective: To facilitate these efforts, a minimally invasive hypertrophic scar model was created in a rabbit ear for the first time based on previous methods used to induce ischemia., Methods: Six New Zealand white rabbits (12 ears total) were studied. First, ischemia was achieved by ligating the cranial artery, cranial vein and central artery, while preserving the caudal artery, caudal vein and central vein, respectively. The relative level of ischemia induced at time of surgery, both baseline and maximum perfusion, was assessed with a fluorescent light-assisted angiography and demonstrated lower rates of perfusion in the ischemic ears. Following vascular injury, a 2-cm full thickness linear wound was created on the ventral ear and closed with 4 - 0 Nylon sutures under high tension. For each rabbit, one ear received a combination of ischemia and wounding with suture tension (n = 6), while the other ear was non-ischemic with wounding and suture tension alone (n = 6)., Results: Four weeks post-operatively, ischemic ears developed scar hypertrophy (histological scar thickness: 1.1 ± 0.2 mm versus 0.5 ± 0.1 mm, p < 0.05)., Conclusion: Herein, we describe a novel, prototypical minimally invasive rabbit ear model of hypertrophic scar formation that can allow investigation of new drugs for scar prevention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza - Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo . After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-β 1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.

The skin epidermis is constantly renewed throughout life 1,2 . Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumour initiation 3 . However, the ways in which oncogenic mutations affect the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumour development are unknown. Here, through multidisciplinary approaches that combine in vivo clonal analysis using intravital microscopy, single-cell analysis and functional analysis, we show how SmoM2-a constitutively active oncogenic mutant version of Smoothened (SMO) that induces the development of basal cell carcinoma-affects clonal competition and tumour initiation in real time. We found that expressing SmoM2 in the ear epidermis of mice induced clonal expansion together with tumour initiation and invasion. By contrast, expressing SmoM2 in the back-skin epidermis led to a clonal expansion that induced lateral cell competition without dermal invasion and tumour formation. Single-cell analysis showed that oncogene expression was associated with a cellular reprogramming of adult interfollicular cells into an embryonic hair follicle progenitor (EHFP) state in the ear but not in the back skin. Comparisons between the ear and the back skin revealed that the dermis has a very different composition in these two skin types, with increased stiffness and a denser collagen I network in the back skin. Decreasing the expression of collagen I in the back skin through treatment with collagenase, chronic UV exposure or natural ageing overcame the natural resistance of back-skin basal cells to undergoing EHFP reprogramming and tumour initiation after SmoM2 expression. Altogether, our study shows that the composition of the extracellular matrix regulates how susceptible different regions of the body are to tumour initiation and invasion., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Ultrashort wave diathermy (USWD) is commonly used in diseases associated with osteoarticular and soft tissue injuries. However, while accelerating wound healing and preventing joint stiffness, there have been few reports on whether it leads to excessive hypertrophic scarring. The aim was to investigate the effects of different doses of USWD on hypertrophic scars., Materials and Methods: A rabbit model of hypertrophic scars was used to determine which dose of USWD reduced scar hyperplasia. The scar thickness was calculated using Sirius red staining. All protein expression levels were determined by western blotting, including fibrosis, collagen deposition, and neoangiogenesis related proteins. Subsequently, flow cytometry and ELISAs were used to determine the proportions of macrophage and inflammatory levels., Results: The wounds with USWD in histopathology showed the dermis was more markedly thickened in the 120 mA group, whereas the wounds with the 60 mA were less raised, comparing with the 0 mA; all detected protein levels were increased significantly, the 120 mA group comparing with the others, including heat shock, fibrosis, and neoangiogenesis, whereas the collagen deposition relative protein levels were decreased, the 60 mA group comparing with Sham group; Finally, in the proportion of macrophages and inflammatory levels the 120 mA group were the highest, and the group Sham was lower than group 60 mA., Conclusions: In hypertrophic scars, the 60 mA USWD could relieve scar formation and inflammatory reactions; however, higher doses could result in opposite consequences.

In adult mammals, skin wounds typically heal by scarring rather than through regeneration. In contrast, "super-healer" Murphy Roths Large (MRL) mice have the unusual ability to regenerate ear punch wounds; however, the molecular basis for this regeneration remains elusive. Here, in hybrid crosses between MRL and non-regenerating mice, we used allele-specific gene expression to identify cis-regulatory variation associated with ear regeneration. Analyzing three major cell populations (immune, fibroblast, and endothelial), we found that genes with cis-regulatory differences specifically in fibroblasts were associated with wound-healing pathways and also co-localized with quantitative trait loci for ear wound-healing. Ectopic treatment with one of these proteins, complement factor H (CFH), accelerated wound repair and induced regeneration in typically fibrotic wounds. Through single-cell RNA sequencing (RNA-seq), we observed that CFH treatment dramatically reduced immune cell recruitment to wounds, suggesting a potential mechanism for CFH's effect. Overall, our results provide insights into the molecular drivers of regeneration with potential clinical implications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Auriculocondylar syndrome (ARCND) is a genetic and rare craniofacial condition caused by abnormal development of the first and second pharyngeal arches during the embryonic stage and is characterized by peculiar auricular malformations (question mark ears), mandibular condyle hypoplasia, micrognathia and other less-frequent features. GNAI3, PLCB4 and EDN1 have been identified as pathogenic genes in this syndrome so far, all of which are implicated in the EDN1-EDNRA signal pathway. Therefore, ARCND is genetically classified as ARCND1, ARCND2 and ARCND3 based on the mutations in GNAI3, PLCB4 and EDN1, respectively. ARCND is inherited in an autosomal dominant or recessive mode with significant intra- and interfamilial phenotypic variation and incomplete penetrance, rendering its diagnosis difficult and therapies individualized. To raise clinicians' awareness of the rare syndrome, we focused on the currently known pathogenesis, pathogenic genes, clinical manifestations and surgical therapies in this review., Competing Interests: Declaration of competing interest All authors reported no conflicts of interest in this work., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Skin is the human body's first line of defense and one of the most exposed organs to environmental chemicals. Allergic contact dermatitis (ACD) is a common skin disease that manifests as a local rash, redness, and skin lesions. The occurrence and development of ACD are influenced by both genetic and environmental factors. Although many scholars have constructed a series of models of ACD in recent years, the experimental protocols of these models are all different, which makes it difficult for readers to establish them well. Therefore, a stable and efficient animal model is of great significance to further study the pathogenesis of atopic dermatitis. In this study, we detail a modeling method using 1-fluoro-2,4-dinitrobenzene (DNFB) to induce ACD-like symptoms in the ears of mice and describe several methods for assessing the severity of dermatitis during modeling. This experimental protocol has been successfully applied in some experiments and has a certain promotional role in the field of ACD research.

Background: Cartilage-cutting and cartilage-sparing techniques are the two types of otoplasty procedures. Because of the significant risk of haematoma, skin necrosis, and ear deformity, cartilage-cutting techniques have been questioned. As a result; suture-based cartilage-sparing procedures such as Mustarde and Furnas suture procedures have grown in popularity. However, these techniques have a tendency for deformity recurrence due to cartilage memory and suture fatigue, as well as the possibility of suture extrusion and pinpricking sensation of the sutures., Methods: In this study, we used a medially based adipo-dermal flap including perichondrium which is elevated from the back of the auricle to cover and support a cartilage-sparing otoplasty, thirty-four patients (14 female and 20 male) were operated using this technique. The medially based perichondrio-adipo-dermal flap is advanced anteriorly and fixed to the helical rim under cover of the distal skin flap. This procedure sought to cover the suture line preventing suture extrusion and support in the repair of the deformity preventing its recurrence., Results: The average operative time was 80min, ranging from 65 to 110min. The patients passed the early postoperative period uneventfully except for 2 patients; one patient (2.9%) developed haematoma, and the other patient developed a small area of necrosis on the new antihelical fold. In late the postoperative period recurrence of the deformity developed in one patient. No patients developed suture extrusion or granuloma., Conclusion: The treatment to repair prominent ears is easy and safe, with benefits such as a natural-looking antihelical fold and minimal tissue stress. The medially or proximally based adipo-dermal flap may help to lower recurrence rates and suture extrusion., (Copyright © 2021 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To investigate the effect and influencing factors of individualized operation for congenital preauricular fistula in children. Methods: The clinical data of 98 cases （109 ears） of congenital preauricular fistula treated in Department of Otolaryngology，Fuzhou Children's Hospital of Fujian Medical University from July 2016 to December 2020 were retrospectively analyzed. According to the characteristics and infection of preauricular fistula，they were divided into common type and variant type，static period of inflammation and period of infection.Individual surgical methods such as classical fistula resection, double fusiform incision and fistula location resection were used respectively.The efficacy，complication and influencing factors of different surgical methods were analyzed. Results: The operation time of classical fistula resection was shorter, and the difference was statistically significant（ t = －2.905 and－3.005 respectively, all P <0.05）. According to the stages and types of fistulas, the selection of individualized surgical methods had achieved good results. There was no significant difference in incision complications and fistula recurrence among different surgical methods （all P >0.05）. Conclusion: Once infection occurs in congenital preauricular fistula, surgical resection should be performed as soon as possible after infection control, or as early as possible after infection maximum control if infection cannot completely subside. Surgical incision design should be individualized, complete resection of fistulas and lesions, minimally invasive and aesthetic., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Auriculocondylar syndrome (ARCND) is a rare genetic disease that affects structures derived from the first and second pharyngeal arches, mainly resulting in micrognathia and auricular malformations. To date, pathogenic variants have been identified in three genes involved in the EDN1-DLX5/6 pathway ( PLCB4 , GNAI3 and EDN1 ) and some cases remain unsolved. Here we studied a large unsolved four-generation family., Methods: We performed linkage analysis, resequencing and Capture-C to investigate the causative variant of this family. To test the pathogenicity of the CNV found, we modelled the disease in patient craniofacial progenitor cells, including induced pluripotent cell (iPSC)-derived neural crest and mesenchymal cells., Results: This study highlights a fourth locus causative of ARCND, represented by a tandem duplication of 430 kb in a candidate region on chromosome 7 defined by linkage analysis. This duplication segregates with the disease in the family (LOD score=2.88) and includes HDAC9 , which is located over 200 kb telomeric to the top candidate gene TWIST1 . Notably, Capture-C analysis revealed multiple cis interactions between the TWIST1 promoter and possible regulatory elements within the duplicated region. Modelling of the disease revealed an increased expression of HDAC9 and its neighbouring gene, TWIST1 , in neural crest cells. We also identified decreased migration of iPSC-derived neural crest cells together with dysregulation of osteogenic differentiation in iPSC-affected mesenchymal stem cells., Conclusion: Our findings support the hypothesis that the 430 kb duplication is causative of the ARCND phenotype in this family and that deregulation of TWIST1 expression during craniofacial development can contribute to the phenotype., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

We report 2 patients who underwent Mohs micrographic surgery (MMS) and operative closure on the ear. Both cases were complicated by necrosis resulting in the formation of auricular defects. These cases highlight the importance of the auricular vasculature and the associated watershed regions during operative planning for MMS as well as the complications that can arise with vascular compromise. This case report also provides a review of the auricular vasculature with special attention to these vulnerable watershed regions.

Purpose: To present a large series ears with tympanic membrane perforations (TMP), to describe their characteristics, and to propose a new classification system based on the pathogenesis of TMP., Methods: This cross-sectional study was conducted at a tertiary university hospital with 1003 ears (792 consecutive patients with TMP in at least 1 ear). Otoendoscopy and audiometry were performed. Perforation measurements and their locations were digitally assessed. TMP with no suggestive signs of previous retraction were classified as Group 1, and those with possible previous retraction were classified as Group 2. Signs of retraction previous to the TMP, symptom length, perforation size and location, status of the contralateral ear, and hearing status were compared., Results: Group 1 comprised 63.5% of the included ears. Compared to Group 2, Group 1 presented a higher rate of central perforations (99% vs. 53%), a shorter duration of symptoms, smaller perforations (mean area: 18.5% vs. 41.4%), a higher rate of perforations in the anterior quadrants, better hearing levels (mean tritonal gap: 23.9 dB vs. 29.2 dB), and a lower rate of abnormal contralateral ears (28% vs. 66%)., Conclusion: The classification of TMP into two groups based on signs of previous retractions is feasible and indicates two different levels of disease severity. While the group without previous signs of retraction comprises ears with more limited disease, membranes with previous retraction seem to show more severe disease and, consequently, a less functional middle ear., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)