Co-culture of RhoA-overexpressed microtia chondrocytes and adipose-derived stem cells in the construction of tissue-engineered ear-shaped cartilage.

Microtia is a congenital auricle dysplasia with a high incidence and tissue engineering technology provides a promising strategy to reconstruct auricles. We previously described that the engineered cartilage constructed from microtia chondrocytes exhibited inferior levels of biochemical and biomechanical properties, which was proposed to be resulted of the decreased migration ability of microtia chondrocytes. In the current study, we found that Rho GTPase members were deficient in microtia chondrocytes. By overexpressing RhoA, Rac1, and CDC42, respectively, we further demonstrated that RhoA took great responsibility for the decreased migration ability of microtia chondrocytes. Moreover, we constructed PGA/PLA scaffold-based cartilages to verify the chondrogenic ability of RhoA overexpressed microtia chondrocytes, and the results showed that overexpressing RhoA was of limited help in improving the quality of microtia chondrocyte engineered cartilage. However, coculture of adipose-derived stem cells (ADSCs) significantly improved the biochemical and biomechanical properties of engineered cartilage. Especially, coculture of RhoA overexpressed microtia chondrocytes and ADSCs produced an excellent effect on the wet weight, cartilage-specific extracellular matrix, and biomechanical property of engineered cartilage. Furthermore, we presented that coculture of RhoA overexpressed microtia chondrocytes and ADSCs combined with human ear-shaped PGA/PLA scaffold and titanium alloy stent fabricated by CAD/CAM and 3D printing technology effectively constructed and maintained auricle structure in vivo. Collectively, our results provide evidence for the essential role of RhoA in microtia chondrocytes and a developed strategy for the construction of patient-specific tissue-engineered auricular cartilage.

Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.

The human auricle has a complex structure, and microtia is a congenital malformation characterized by decreased size and loss of elaborate structure in the affected ear with a high incidence. Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility-related genes and subsequent confirmations, active Rac1 (Rac1-GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1-GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, Bmp5se/J and Prkralear-3J/GrsrJ. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

A quick and innovative pipeline for producing chondrocyte-homing peptide-modified extracellular vesicles by three-dimensional dynamic culture of hADSCs spheroids to modulate the fate of remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment.

BACKGROUND: Extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADSCs) have shown great therapeutic potential in plastic and reconstructive surgery. However, the limited production and functional molecule loading of EVs hinder their clinical translation. Traditional two-dimensional culture of hADSCs results in stemness loss and cellular senescence, which is unfavorable for the production and functional molecule loading of EVs. Recent advances in regenerative medicine advocate for the use of three-dimensional culture of hADSCs to produce EVs, as it more accurately simulates their physiological state. Moreover, the successful application of EVs in tissue engineering relies on the targeted delivery of EVs to cells within biomaterial scaffolds. METHODS AND RESULTS: The hADSCs spheroids and hADSCs gelatin methacrylate (GelMA) microspheres are utilized to produce three-dimensional cultured EVs, corresponding to hADSCs spheroids-EVs and hADSCs microspheres-EVs respectively. hADSCs spheroids-EVs demonstrate excellent production and functional molecule loading compared with hADSCs microspheres-EVs. The upregulation of eight miRNAs (i.e. hsa-miR-486-5p, hsa-miR-423-5p, hsa-miR-92a-3p, hsa-miR-122-5p, hsa-miR-223-3p, hsa-miR-320a, hsa-miR-126-3p, and hsa-miR-25-3p) and the downregulation of hsa-miR-146b-5p within hADSCs spheroids-EVs show the potential of improving the fate of remaining ear chondrocytes and promoting cartilage formation probably through integrated regulatory mechanisms. Additionally, a quick and innovative pipeline is developed for isolating chondrocyte homing peptide-modified EVs (CHP-EVs) from three-dimensional dynamic cultures of hADSCs spheroids. CHP-EVs are produced by genetically fusing a CHP at the N-terminus of the exosomal surface protein LAMP2B. The CHP + LAMP2B-transfected hADSCs spheroids were cultured with wave motion to promote the secretion of CHP-EVs. A harvesting method is used to enable the time-dependent collection of CHP-EVs. The pipeline is easy to set up and quick to use for the isolation of CHP-EVs. Compared with nontagged EVs, CHP-EVs penetrate the biomaterial scaffolds and specifically deliver the therapeutic miRNAs to the remaining ear chondrocytes. Functionally, CHP-EVs show a major effect on promoting cell proliferation, reducing cell apoptosis and enhancing cartilage formation in remaining ear chondrocytes in the M1 macrophage-infiltrated microenvironment. CONCLUSIONS: In summary, an innovative pipeline is developed to obtain CHP-EVs from three-dimensional dynamic culture of hADSCs spheroids. This pipeline can be customized to increase EVs production and functional molecule loading, which meets the requirements for regulating remaining ear chondrocyte fate in the M1 macrophage-infiltrated microenvironment.

New Method Using Local Affected Cartilage and Flap for the Cleft in Question Mark Ear.

BACKGROUND: As a rare auricular deformity, despite numerous surgical procedures for correcting moderate-to-severe question mark ears described in past studies, there remains a need to explore a more cost-effective approach. The optimal utilization of ear cartilage and surrounding skin while achieving superior outcomes continues to pose a significant challenge. METHODS: From 2018 to 2023, twenty-four patients with unilateral question mark ear were enrolled in this study. Seven of them were severe type deformities (absence of lower part of auricle), and seventeen were moderate (only cleft between helix and lobule). All patients were treated with new method using local cartilage and flap without damage in unaffected area. RESULTS: All patients were satisfied with significant improvement of question mark ear and the overall symmetrical appearance. The surgical scar was not obvious. No complications were observed. The follow-up period revealed that the corrective procedure kept producing the symmetrical and cosmetic results. CONCLUSION: Our new method enables optimal utilization of deformed tissue and surrounding skin, rendering this method effective and reliable for correcting moderate-to-severe question mark ears. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Effects of Radial Cartilage Incision on the Growth of Rabbit Ear.

OBJECTIVES: Recently, radial cartilage incision (first-stage) at an early age combined with free auricular composite tissue grafting (second-stage) can effectively correct the concha-type microtia with the moderate or severe folded cartilage in the middle and upper third auricle, but radial cartilage incision's effects on the growth of the ear remain to be determined. The authors aimed to evaluate the effects of radial cartilage incision in young rabbits model. METHODS: Ten New Zealand white rabbits were included in our experiment. Two ears of each rabbit were divided randomly into two groups. The experimental group was operated with radial cartilage incision, and no intervention was given to the control group. The ear width, length, and perimeter were noted every two weeks. Auricular surface area was noted at 4 and 22 weeks old. The repeated measures ANOVA was used to describe ears' growth trend. A paired-sample's t test is conducted to test whether there are significant differences among the variables through the SPSS25.0 software. RESULTS: The growth tendencies of the ear length, width, and perimeter were observed and analyzed. The growth curves of the experimental ears were similar to that of the control. There was no significant difference in the increased ratio of surface area among the two groups. The cartilage of the experimental ears showed no change in biomechanical properties compared to that of control group. CONCLUSION: This study shows that radial cartilage incision at an early age does not influence the growth of rabbit ear length, width, perimeter, and surface area and also does not change the biomechanical properties of the cartilage. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Minimally Invasive Costal Cartilage Harvesting Incision for Chest Deformity in Microtia Reconstruction.

BACKGROUND: Chest deformity is a potential complication associated with auricular reconstruction using autologous costal cartilage. The impact of the incision size employed for costal cartilage harvesting on chest deformities remains unclear. This study aimed to investigate the correlation between the incision size used for harvesting costal cartilage and the occurrence of chest deformities. METHODS: We retrospectively analyzed patients who underwent ear reconstruction using autologous costal cartilage between June 2021 and September 2022. The patients were categorized into two groups based on the size of the costal cartilage incision: large and small. Chest computed tomography (CT) was performed 18-24 months postoperatively, followed by three-dimensional color map quantification to assess the degree of asymmetry of the chest surface. Subsequently, quantitative data analysis was performed to compare the extent of chest asymmetry between the large- and small-incision groups. The Visual Analog Scale (VAS) was used to assess patient satisfaction with chest morphology. RESULTS: This study included 62 patients, with an equal distribution of 31 in each group. The mean asymmetry value of the small and large incision groups was -3.15 ± 1.88 and -5.27 ± 3.63, respectively. Moreover, the mean VAS score for the small and large incision groups was 7.48 ± 0.72 and 5.09 ± 0.94, respectively. Statistically significant differences were observed between the two groups. CONCLUSIONS: Small incision costal cartilage harvesting can effectively alleviate the severity of chest deformities and significantly enhance patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Genetically engineered chondrocytes overexpressing elastin improve cell retention and chondrogenesis in a three-dimensional GelMA culture system.

Elastic cartilage possesses many elastic fibers and has a high degree of elasticity. However, insufficient elastic fiber production remains unsolved in elastic cartilage tissue engineering. Exogenous elastin is difficult to degrade and violates cell proliferation and migration during cartilage regeneration. Moreover, exogenous elastic fibers are difficult to assemble with endogenous extracellular matrix components. We produced genetically engineered chondrocytes overexpressing elastin to boost endogenous elastic fiber production. After identifying that genetic manipulation hardly impacted the cell viability and chondrogenesis of chondrocytes, we co-cultured genetically engineered chondrocytes with untreated chondrocytes in a three-dimensional gelatin methacryloyl (GelMA) system. In vitro study showed that the co-culture system produced more elastic fibers and increased cell retention, resulting in strengthened mechanics than the control system with untreated chondrocytes. Moreover, in vivo implantation revealed that the co-culture GelMA system greatly resisted host tissue invasion by promoting elastic fiber production and cartilage tissue regeneration compared with the control system. In summary, our study indicated that genetically engineered chondrocytes overexpressing elastin are efficient and safe for promoting elastic fiber production and cartilage regeneration in elastic cartilage tissue engineering.

Quantitative T2 mapping monitoring the maturation of engineered elastic cartilage in a rabbit model.

BACKGROUND: Cartilage tissue engineering provides a promising approach to reconstruct craniofacial defects, and a noninvasive method is needed to assess its effectiveness. Although magnetic resonance imaging (MRI) has been used to evaluate articular cartilage in vivo, few studies focused on its feasibility in monitoring engineered elastic cartilage (EC). METHODS: Auricular cartilage, silk fibroin (SF) scaffold, and EC consisting of rabbit auricular chondrocytes and SF scaffold were transplanted subcutaneously into the rabbit back. In eight weeks after transplantation, grafts were imaged by MRI using PROSET, PDW VISTA SPAIR, 3D T2 VISTA, 2D MIXED T2 Multislice, and SAG TE multiecho sequences, followed by histological examination and biochemical analysis. Statistical analyses were performed to identify the association between T2 values and biochemical indicator values of EC. RESULTS: In vivo imaging shows that 2D MIXED T2 Multislice sequence (T2 mapping) clearly distinguished the native cartilage, engineered cartilage and fibrous tissue. T2 values showed high correlations with cartilage-specific biochemical parameters at different time points, especially the elastic cartilage specific protein elastin (ELN, r= -0.939, P < 0.001). CONCLUSION: Quantitative T2 mapping can effectively detect the in vivo maturity of engineered elastic cartilage after subcutaneously transplantation. This study would promote the clinical application of MRI T2 mapping in monitoring engineered elastic cartilage in the repair of craniofacial defects.

Changes in the Transcriptome-Associated Co-Expression Profile of Embryonic External Ear Development After the BMP5 Gene Mutation.

This study aimed to perform an association analysis of the full transcriptome in Bmp5 short-ear mice during the development of the external ear in mouse embryos using advanced sequencing techniques. To understand the changes in gene regulation and expression of BMP5 gene mutations involved in the external ear embryonic development of mice, external ear tissues of mouse embryos developed to E15.5 and E17.5 were obtained using a BMP5 short-ear mouse model. The association analysis of the full transcriptome mainly involved the analysis of lncRNA and mRNA associations, the analysis of lncRNA and miRNA associations, the analysis of miRNA and mRNA associations, the analysis of circRNA and mRNA associations and circRNA, miRNA, and mRNA associations. The results showed that regulation of the full transcriptome is associated with external ear development in BMP5 short-ear mouse embryos, and some key regulatory changes in full transcriptome after BMP5 gene point mutation are different. This study will provide a new clue to investigate the mechanism underlying the regulation of mouse external ear development by the full transcriptome.

Changes in Transcriptome-Associated Co-Expression Profile of Embryonic External Ear Development After Prkra Gene Mutation.

The aim was to understand the changes in gene expression during the mouse external ear embryonic development in the full transcriptomes of mice with a point mutation in the Prkra gene, the outer ear tissues of mouse embryos were developed to embryonic day (E)15.5 and E17.5, and a Prkra Little-ear mouse model was obtained. The purpose of this study was to perform a whole transcriptome association analysis of the Prkra Little-ear mouse model during external ear embryonic development using advanced sequencing techniques. The association analysis of the full transcriptome mainly included lncRNA and mRNA association analysis, lncRNA and miRNA association analysis, miRNA and mRNA association analysis, circRNA and mRNA association analysis, circRNA, miRNA, and mRNA association analysis, and lncRNA, miRNA, and mRNA association analysis. The results of the correlation analysis showed that in the Prkra Little-ear mouse embryo development of the external ear was regulated by whole transcriptome and that these changes were different in wild-type mice. This study provides a new concept for elucidating the mechanism of the regulation of mouse external ear development.

Point Mutation in Prkra Alters miRNA Expression During Embryonic External Ear Development.

Microtia is a congenital malformation of the external ear that can lead to conductive hearing impairment. In this study, we investigated the role of the Prkra gene in external ear development. We used advanced sequencing techniques to evaluate the differential expression of microRNAs (miRNAs) involved in external ear development in mouse embryos after point mutation in the Prkra gene. The Prkra Little ear mouse model was used to obtain mouse embryos at the E15.5 and E17.5 developmental stages, and changes in miRNA expression profiles were detected. Gene ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were performed on differentially expressed miRNAs, and existing and new miRNAs were studied. miRNAs were observed to be involved in multiple signaling pathways during the E15.5 and E17.5 developmental stages. The results show a correlation between miRNA regulation and external ear development in Prkra Little ear mice, and differences were detected in key regulatory miRNAs owing to point mutations in the Prkra gene. This study provides new insights into the biological mechanisms through which miRNAs regulate external ear development in mouse embryos. Changes in the mouse miRNA expression profiles can also provide insights into the pathogenesis of human congenital microtia at the level of miRNA regulation.

Prkra Mutation Alters Long Noncoding RNA Expression During Embryonic External Ear Development.

Point mutations in the Prkra gene result in abnormalities in mouse external ear development; however, the regulatory mechanisms underlying this phenotype are unclear. This study evaluated long noncoding RNA (lncRNA) expression profiles in the outer ear tissues of embryos at E15.5 and E17.5 from the Prkra little ear mouse model using transcriptome sequencing. Differentially expressed lncRNAs between the experimental and control groups were identified and evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The results revealed various lncRNAs that contribute to the external ear development in Prkra mutant mice, some of which were involved in multiple developmental signaling pathways. There were expression changes in some key regulatory lncRNAs after point mutations in the Prkra gene, some of which were involved in multiple developmental signaling pathways, such as the Hippo, MAPK, and ErbB signaling pathways. These results provide insight into the regulatory mechanism underlying external ear embryonic development and reveal candidate lncRNAs.

Bmp5 Mutation Alters mRNA Expression During External Ear Development.

To understand changes in gene regulation and mRNA expression in external ear development, we used a bone morphogenetic protein 5 (BMP5) short-ear mouse model. External ear tissues at E15.5 and E17.5 were collected, and mRNA expression profiles were analyzed. Upregulated and downregulated mRNA expression was identified using find_circ and CIRI2 software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the differentially expressed mRNAs. Alterations in related signal pathways were identified from the upregulated and downregulated mRNA transcripts. The results showed a correlation between the mRNA expression during external ear development in BMP5 short-ear mice, including key regulatory mRNA changes after point mutations of the Bmp5 gene. This study provides evidence for the mechanism underlying mRNA regulation during external ear development. Changes in mRNA expression profiles also provide clues for future studies regarding the regulatory mechanisms underlying external ear development.

Prkra Mutation Alters mRNA Expression During Embryonic External Ear Development.

To understand the changes in mRNA expression during the embryonic development of the external mouse ear after the point mutation of the Prkra gene, Prkra short ear mouse model was used to study the development of the embryonic external ear. The tissues of the embryonic external ear were obtained when mouse embryos developed to E15.5 and E17.5. The changes in the mRNA expression profile were detected and analyzed. Find_circ and CIRI2 softwares were used to identify the upregulated and down-regulated expression of mRNA in the experimental and control groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were conducted on the differentially expressed mRNA, and the related signal pathways were analyzed after the upregulation and down-regulation of mRNA expression. This study aimed to understand the regulation of mRNA expression in Prkra short-ear mice during the external ear development in embryos. The results showed a correlation between abnormally expressed mRNA and signal pathways and the regulation of the development of the external ear of Prkra short-ear mice, and there were differences in some key regulatory mRNA changes after the Prkra gene point mutation. This study will provide a new clue for the mechanism of mRNA regulating the development of the external mouse ear. The change in mRNA expression profile can also provide clues for studying the biological regulation mechanism of external ear embryonic development.

Effect of Mechanical Tension on the Long-Chain Noncoding RNA Expression Profile of Human Skin Regeneration.

This study investigates the potential gene regulation of long-chain noncoding RNAs (lncRNAs) during skin regeneration by analyzing the changes in the lncRNA expression profile during skin regeneration under mechanical tension. Through the effect of mechanical tension on human skin tissue, the authors observed that after the accelerated differentiation and proliferation of skin epidermal cells, the lncRNA expression profile was compared with that of normal epidermal cells, and differential expression of lncRNA in skin tissue was found. Fifty-three lncRNAs were differentially expressed between the experimental and control groups, and compared with the control group, 22 lncRNAs were upregulated and 31 lncRNAs were downregulated in the experimental group. In addition, through the annotation of the functions of gene ontology and kyoto encyclopedia of genes and genomes, it was further clarified that the main signaling pathway of lncRNAs in the process of skin tissue expansion is involved in the regulation of skin tissue regeneration, and the regulatory network of lncRNAs and microRNAs was established. The results of this study will provide a theoretical basis for the mechanism of lncRNA regulation of skin regeneration, and changes in the lncRNA expression profile can also provide clues for the study of the biological regulation mechanism of skin regeneration.

Changes in the Long Noncoding RNA Expression Profile in the Development of the Embryonic External Ear After BMP5 Gene Mutation.

To understand the role of long noncoding RNA (lncRNA) gene regulation and changes in expression in mouse external ear embryonic development, a BMP5 short ear mouse model was used to measure changes in the lncRNA expression in the outer ear tissues of mouse embryos developed to E15.5 and E17.5 using high-throughput sequencing. The changes in lncRNA expression were identified using find_circ and CIRI2 software, and functional analyses were performed using gene ontology and the Kyoto encyclopedia of genes and genomes annotations of differentially expressed lncRNAs. The results show a correlation between the regulation of lncRNA and some key regulatory lncRNA changes after point mutations in BMP5 . This study provides new insights into the mechanism, by which lncRNAs regulate the development of the mouse's external ear. The change in lncRNA expression profiles can also provide clues for the study of the regulatory mechanisms of external ear embryonic development.

Functional Pathway and Process Enrichment Analysis of Genes Associated With Morphological Abnormalities of the Outer Ear.

Congenital anomalies of the outer ear are common birth defects, including a variety of congenital deformities or malformations ranging from mild structural anomalies to total absence of the ear. Despite its high incidence and detrimental impact on patients, the etiology of outer ear abnormalities remains poorly understood. The goal of this study was to summarize the related genes and improve our understanding of the genetic etiology of morphological abnormalities of the outer ear. Human Phenotype Ontology (HPO) database, Mouse Genome Informatics (MGI) database, and PubMed search engine were used to acquire the genes associated with abnormal human or mouse outer ear. Metascape was employed on the genes above to conduct functional annotation, pathway and process enrichment analysis, protein-protein interaction network analysis, and MCODE component analysis. After a comprehensive review of the databases and literature, we identified 394 human genes and 148 mouse genes that have been associated with abnormal phenotypes of the outer ear, and we identified several biological pathways for human and mouse respectively. Especially, the analysis of common genes shared by human and mouse emphasized the importance of certain genes ( PAX6 , PBX1 , HOXA1 , HOXA2 , TBX1 , TBX15 , PRRX1 , and HMX1 ) in the embryonic development of the external ear. Through our analysis of genes associated with morphological abnormalities of the outer ear, the authors have shown that embryonic development pathways take important roles in the morphogenesis of abnormal external ear and highlighted some potential genetic drivers.

Correlations Among Clinical Phenotypes, Radiological Examination Indexes, and Hearing Status in Congenital Microtia.

Microtia is a congenital malformation of the external ear that often presents with other anatomical abnormalities and ipsilateral hearing loss (HL). The aim of this study was to present the correlation among important phenotypic abnormalities in microtia and their relationship with HL in a clinical population in China. In this study, a retrospective analysis was conducted on 307 patients diagnosed with microtia who visited the Department of Auricular Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, for surgical auricle reconstruction from April 2021 to April 2022. Standardized classification of ear malformations, craniofacial CT scans, and pure tone audiometric data were collected, and statistical analyses were performed using the rank sum test, Kruskal-Wallis test, and Spearman's rank correlation coefficient. The results showed that group differences between ear malformation and variations in the development of mandible, external auditory canal (EAC), and mastoid pneumatization were statistically significant and each had a positive correlation. Among them, the correlation between development of ear and EAC was the most significant (Ρ=0.72). Besides, the severity of HL (97% were conductive) was positively correlated with ear and EAC dysplasia with or without mandibular hypoplasia. Based on the statistical analysis of the correlation between ear malformation and HL, the authors strongly recommend that facial phenotype reconstruction and hearing improvement of microtia should be considered comprehensively, regardless of whether children with microtia show HL or not, early diagnosis of audiology evaluation and appropriate intervention measures should be implemented.

The effect of platelet-rich plasma injection on chronic Achilles tendinopathy and acute Achilles tendon rupture.

Several clinical trials exploring the effect of platelet-rich plasma (PRP) on Achilles tendon rupture (ATR) or Achilles tendinopathy (AT) have been published. However, current evidence is limited to small-sized trials. This study aims to evaluate whether PRP improves the outcomes of ATR or AT. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials comparing PRP injection versus placebo for ATR or AT. Eleven studies with 574 patients were included. Quantitative synthesis suggested that compared with placebo, AT patients in PRP group had higher VISA-A score improvement at six-week follow-up (mean difference (MD) = 2.64; 95% CI) = 1.12 to 4.15). However, there was no significant difference between two groups for VISA-A score improvement at three-month follow-up (MD = 0.93; 95% CI = -2.75 to 4.62), or 6-month follow-up (MD = 5.46; 95% CI = -1.19 to 12.11). In ATR patients, quantitative synthesis suggested that no significant difference was seen between PRP and control group at 3-month, 6-month, and 1-year follow-up. In addition, no significant difference was detected between the two groups in improving tendon thickness and pain for AT patients, and no significant difference was seen in improving heel-rise work, maximum heel-rise height, dorsal and plantar flexion, rate of returning to sports activities, and complication for ATR patients. To conclude, no evidence indicates that PRP injection can improve the patient-reported/clinical/functional outcomes of AT or ATR. The increasing times of PRP injection could improve the outcomes, and further clinical randomized controlled trials are expected to be conducted to verify this hypothesis.