Objective:To construct a virtual-real interactive system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility of applying HE-01 in ear reconstruction.Methods:Six volunteers (3 males and 3 females, average age: 20.5 years old) and six patients with microtia(3 males and 3 females, average age: 7.6 years old) were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. The Mimics Research 21.0 software and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of different colors (red, green, blue and skin color) of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of six volunteers (12 ears) showed a high registration accuracy (average error rate 2.3%-2.4%, less than 2.7% of the bilateral auricle size difference of normal people), low tracking delay (six volunteers were all less than 0.1 s), and best green and red display effect of virtual auricle guide under different angles (-60°, -30°, 0°, 30°, 60°). Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

Objective:To construct a virtual-real interactive system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility of applying HE-01 in ear reconstruction.Methods:Six volunteers (3 males and 3 females, average age: 20.5 years old) and six patients with microtia(3 males and 3 females, average age: 7.6 years old) were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. The Mimics Research 21.0 software and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of different colors (red, green, blue and skin color) of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of six volunteers (12 ears) showed a high registration accuracy (average error rate 2.3%-2.4%, less than 2.7% of the bilateral auricle size difference of normal people), low tracking delay (six volunteers were all less than 0.1 s), and best green and red display effect of virtual auricle guide under different angles (-60°, -30°, 0°, 30°, 60°). Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

Objective:To explore the expression of hypoxia-inducible factor-1α (HIF-1α) in different types of congenital microtia chondrocytes and normal ear chondrocytes, and the relationship with oxygen concentrations.Methods:The experimental samples were from the patients with unilateral congenital microtia admitted to Plastic Surgery Hospital of Chinese Academy of Medical Sciences during September 1st, 2021 to October 31st, 2022, including 6 cases of unilateral lobular type congenital microtia (experimental group 1), 6 cases of conchal type (experimental group 2), and 6 cases of normal ear cartilage (experimental group 3). And auricle chondrocytes of each group were extracted respectively. The chondrocytes of each group were cultured in an incubator with an oxygen concentrations of 21%, 10%, 5%, and 1% respectively. After 12 h, total RNA was collected and the expression of HIF-1α at the mRNA level was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Immunofluorescence staining was used to detect the expression of HIF-1α protein in chondrocytes. Statistical analysis was performed using GraphPad Prism 8.0 software. One-way ANOVA was used for comparison between groups, and SNK test was used for pairwise comparison. P<0.05 was considered statistically significant. Results:RT-qPCR results showed the relative expression levels of HIF-1α mRNA in ear chondrocytes under 21%, 10%, 5%, and 1% oxygen concentrations. In experimental group 1 the relative expression levels of HIF-1α mRNA were 0.031 8±0.006 0, 0.043 4±0.001 0, 0.049 5±0.000 9, 0.030 5±0.001 0 respectively; experimental group 2, 0.036 9±0.000 6, 0.047 4±0.000 8, 0.054 1±0.000 4, 0.034 1±0.001 8 respectively; experimental group 3, 0.041 6±0.000 4, 0.055 6±0.000 6, 0.070 1±0.001 9, 0.077 2±0.000 9 respectively; the difference of relative expression of HIF-1α mRNA in the three groups was statistically significant under the condition of 21% and 5% oxygen concentration ( P<0.01). Immunofluorescence staining showed that the HIF-1α protein in experimental groups 1 and 2 was partially located in the nucleus and partially located in the cytoplasm, while in the experimental group 3 it was located in the nucleus at 5% oxygen concentration. Conclusion:HIF-1α is expressed in both types of lobular and conchal congenital microtia and normal ear chondrocytes, and the expression level is negatively correlated with the severity of the deformity. When oxygen concentration varied from 21% to 1%, the changing trend of HIF-1α mRNA in type lobular and type conchal microtia is similar, and the expression level is negatively correlated with the severity of the abnormality, and the peak value appeared at 5% oxygen concentration, decreased at 1% oxygen concentration, but continued to increase in normal ear chondrocytes. At 5% oxygen concentration, the location of HIF-1α protein in the nucleus of chondrocytes with microtia is different from normal chondrocytes.

Objective:To construct a system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility the application of HE-01 in ear reconstruction.Methods:Six volunteers and six patients with microtia were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. Mimics Research and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of volunteers showed that under different angles, the registration accuracy was high (less than 2.7% of the bilateral auricle size difference of normal people), the tracking delay was low (less than 0.1s), and the green and red display effect of virtual auricle guide was the best. Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

Objective:To explore the expression of hypoxia-inducible factor-1α (HIF-1α) in different types of congenital microtia chondrocytes and normal ear chondrocytes, and the relationship with oxygen concentrations.Methods:The experimental samples were from the patients with unilateral congenital microtia admitted to Plastic Surgery Hospital of Chinese Academy of Medical Sciences during September 1st, 2021 to October 31st, 2022, including 6 cases of unilateral lobular type congenital microtia (experimental group 1), 6 cases of conchal type (experimental group 2), and 6 cases of normal ear cartilage (experimental group 3). And auricle chondrocytes of each group were extracted respectively. The chondrocytes of each group were cultured in an incubator with an oxygen concentrations of 21%, 10%, 5%, and 1% respectively. After 12 h, total RNA was collected and the expression of HIF-1α at the mRNA level was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Immunofluorescence staining was used to detect the expression of HIF-1α protein in chondrocytes. Statistical analysis was performed using GraphPad Prism 8.0 software. One-way ANOVA was used for comparison between groups, and SNK test was used for pairwise comparison. P<0.05 was considered statistically significant. Results:RT-qPCR results showed the relative expression levels of HIF-1α mRNA in ear chondrocytes under 21%, 10%, 5%, and 1% oxygen concentrations. In experimental group 1 the relative expression levels of HIF-1α mRNA were 0.031 8±0.006 0, 0.043 4±0.001 0, 0.049 5±0.000 9, 0.030 5±0.001 0 respectively; experimental group 2, 0.036 9±0.000 6, 0.047 4±0.000 8, 0.054 1±0.000 4, 0.034 1±0.001 8 respectively; experimental group 3, 0.041 6±0.000 4, 0.055 6±0.000 6, 0.070 1±0.001 9, 0.077 2±0.000 9 respectively; the difference of relative expression of HIF-1α mRNA in the three groups was statistically significant under the condition of 21% and 5% oxygen concentration ( P<0.01). Immunofluorescence staining showed that the HIF-1α protein in experimental groups 1 and 2 was partially located in the nucleus and partially located in the cytoplasm, while in the experimental group 3 it was located in the nucleus at 5% oxygen concentration. Conclusion:HIF-1α is expressed in both types of lobular and conchal congenital microtia and normal ear chondrocytes, and the expression level is negatively correlated with the severity of the deformity. When oxygen concentration varied from 21% to 1%, the changing trend of HIF-1α mRNA in type lobular and type conchal microtia is similar, and the expression level is negatively correlated with the severity of the abnormality, and the peak value appeared at 5% oxygen concentration, decreased at 1% oxygen concentration, but continued to increase in normal ear chondrocytes. At 5% oxygen concentration, the location of HIF-1α protein in the nucleus of chondrocytes with microtia is different from normal chondrocytes.

Objective:To construct a system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility the application of HE-01 in ear reconstruction.Methods:Six volunteers and six patients with microtia were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. Mimics Research and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of volunteers showed that under different angles, the registration accuracy was high (less than 2.7% of the bilateral auricle size difference of normal people), the tracking delay was low (less than 0.1s), and the green and red display effect of virtual auricle guide was the best. Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

Objective:To establish a prognosis model of cutaneous melanoma through bioinformatics analysis of glycolysis-related genes, therefore enhancingthe precision of classification and treatment.Methods:The mRNA expression profiles and clinical data of melanoma patients (470 cases in total, including 290 males and 180 females) in The Cancer Genome Atlas (TCGA) database were obtained, data of normal skin tissue samples (812 cases, including 467 males and 345 females) in GTEx database were used as controls. Gene set enrichment analysis (GSEA) was used to extract differentially expressed genes in the glycolysis pathway that significantly associated with melanoma. The mRNAs significantly correlated with melanoma prognosis were screened by Cox regression analysis, and the prognostic risk score (RS) model of melanoma patients was constructed. According to the median RS value of the risk scoring model, 450 melanoma patients who were eligible for survival analysis were divided into the high-risk group and the low-risk group, and the difference in survival time and survival rate between the two groups was analyzed. In addition, ROC curves were drawn to evaluate the predictive value of RS value on the mortality risk of melanoma patients at 10 and 20 years.Results:GSEA analysis showed that the glycolysis-related REACTOME_GLYCOLYSIS pathway was significantly enriched in melanoma samples, with a standard differentiation score (NES) of 1.74 and a false discovery rate (FDR) of 0.016. By univariate and multivariate Cox regression analysis of 117 differentially expressed genes (71 up-regulated and 46 down-regulated) in this pathway, 9 mRNA molecules closely related to the prognosis of cutaneous melanoma were found out, including four protective factors (STAT3, MLXIPL, IDUA and AURKA) and five risk factors (KIF20A, PGM1, GYS1, ALG1 and HDAC4). According to the regression coefficient of multivariate Cox regression analysis and mRNA expression level of each gene, the prognostic risk scoring model was established: RS = 0.31×KIF20A + 0.19× PGM1-0.27 ×STAT3 + 0.24× GYS1-0.25 × MLXIPL-0.19 ×IDUA + 0.33× ALG1-0.28 ×AURKA + 0.26×HDAC4. The median RS value of 0.83 was used as the cut-off value, and the patients were divided into the high-risk group (225 cases) and the low-risk group (225 cases). The overall survival time of the high-risk group was (6.72±0.55) years, which was significantly lower than that of the low-risk group (13.60±1.03) years ( P<0.001). The 10-year and 20-year survival rates in the high-risk group were significantly lower than those in the low-risk group (24.1% vs. 50.9%; 0 vs. 25.2%; P<0.001); the area under the ROC curve of RS value was 0.730 and 0.749 for 10-year and 20-year survival prediction of melanoma patients, respectively. Multivariate Cox regression analysis showed that RS value was an independent prognostic factor of melanoma. Conclusions:The risk-score model could effectively group the melanoma patients according to the prognosis, and had high degree of credibility. This model may be a new method to guide the accurate targeting treatment of melanoma.

Objective:To investigate the clinical effect of reconstructed tragus with hinge-shaped cartilage flap during the third stage reconstructive surgery in patients with microtia.Methods:From January 2018 to January 2019, the data of the patients with unilateral microtia of residual ear Type Ⅲ treated in the Seventh Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. The residual ear tissue preserved in the second stage operation was used to reconstruct the tragus during the third stage operation, and the external auditory meatus was simulated with medium-thickness skin grafting. Postoperative changes were observed in the width, height, and symmetry of the tragus.Results:A total of 31 children with microtia were included, including 19 males and 12 females, aged from 6 to 14 years (mean 8 years), right ear ( n=16) and left ear ( n=15). Postoperative blood supply was good, and the incisions healed primarily. The patient’s immediate postoperative tragus width and height were slightly greater than the preoperative design requirements. After follow-up of 3-6 months, the width of the contralateral tragus was (1.05±0.12) cm, while the reconstructed tragus width was (0.98±0.17) cm. The difference was not statistically significant ( P=0.328). The height of the contralateral tragus was (0.53±0.08) cm, while the reconstructed tragus width was (0.55±0.08) cm. The difference was not statistically significant ( P=0.741). The reconstructed tragus had a good three-dimensional structure and stable shape, and the simulated shape of the external auditory meatus was good. Patients can wear earphones to meet the needs of daily life. Conclusions:Using residual ear cartilage to reconstruct the tragus by flapping hinge-cartilage can improve the three-dimensional structure of the auricle and skin grafting to the concha cavity posterior to the tragus can simulate external auditory meatus. The reconstructed ear resembles the healthy one and meets the need of wearing earphones.

Objective:To establish a prognosis model of cutaneous melanoma through bioinformatics analysis of glycolysis-related genes, therefore enhancingthe precision of classification and treatment.Methods:The mRNA expression profiles and clinical data of melanoma patients (470 cases in total, including 290 males and 180 females) in The Cancer Genome Atlas (TCGA) database were obtained, data of normal skin tissue samples (812 cases, including 467 males and 345 females) in GTEx database were used as controls. Gene set enrichment analysis (GSEA) was used to extract differentially expressed genes in the glycolysis pathway that significantly associated with melanoma. The mRNAs significantly correlated with melanoma prognosis were screened by Cox regression analysis, and the prognostic risk score (RS) model of melanoma patients was constructed. According to the median RS value of the risk scoring model, 450 melanoma patients who were eligible for survival analysis were divided into the high-risk group and the low-risk group, and the difference in survival time and survival rate between the two groups was analyzed. In addition, ROC curves were drawn to evaluate the predictive value of RS value on the mortality risk of melanoma patients at 10 and 20 years.Results:GSEA analysis showed that the glycolysis-related REACTOME_GLYCOLYSIS pathway was significantly enriched in melanoma samples, with a standard differentiation score (NES) of 1.74 and a false discovery rate (FDR) of 0.016. By univariate and multivariate Cox regression analysis of 117 differentially expressed genes (71 up-regulated and 46 down-regulated) in this pathway, 9 mRNA molecules closely related to the prognosis of cutaneous melanoma were found out, including four protective factors (STAT3, MLXIPL, IDUA and AURKA) and five risk factors (KIF20A, PGM1, GYS1, ALG1 and HDAC4). According to the regression coefficient of multivariate Cox regression analysis and mRNA expression level of each gene, the prognostic risk scoring model was established: RS = 0.31×KIF20A + 0.19× PGM1-0.27 ×STAT3 + 0.24× GYS1-0.25 × MLXIPL-0.19 ×IDUA + 0.33× ALG1-0.28 ×AURKA + 0.26×HDAC4. The median RS value of 0.83 was used as the cut-off value, and the patients were divided into the high-risk group (225 cases) and the low-risk group (225 cases). The overall survival time of the high-risk group was (6.72±0.55) years, which was significantly lower than that of the low-risk group (13.60±1.03) years ( P<0.001). The 10-year and 20-year survival rates in the high-risk group were significantly lower than those in the low-risk group (24.1% vs. 50.9%; 0 vs. 25.2%; P<0.001); the area under the ROC curve of RS value was 0.730 and 0.749 for 10-year and 20-year survival prediction of melanoma patients, respectively. Multivariate Cox regression analysis showed that RS value was an independent prognostic factor of melanoma. Conclusions:The risk-score model could effectively group the melanoma patients according to the prognosis, and had high degree of credibility. This model may be a new method to guide the accurate targeting treatment of melanoma.

Objective:To investigate the clinical effect of reconstructed tragus with hinge-shaped cartilage flap during the third stage reconstructive surgery in patients with microtia.Methods:From January 2018 to January 2019, the data of the patients with unilateral microtia of residual ear Type Ⅲ treated in the Seventh Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. The residual ear tissue preserved in the second stage operation was used to reconstruct the tragus during the third stage operation, and the external auditory meatus was simulated with medium-thickness skin grafting. Postoperative changes were observed in the width, height, and symmetry of the tragus.Results:A total of 31 children with microtia were included, including 19 males and 12 females, aged from 6 to 14 years (mean 8 years), right ear ( n=16) and left ear ( n=15). Postoperative blood supply was good, and the incisions healed primarily. The patient’s immediate postoperative tragus width and height were slightly greater than the preoperative design requirements. After follow-up of 3-6 months, the width of the contralateral tragus was (1.05±0.12) cm, while the reconstructed tragus width was (0.98±0.17) cm. The difference was not statistically significant ( P=0.328). The height of the contralateral tragus was (0.53±0.08) cm, while the reconstructed tragus width was (0.55±0.08) cm. The difference was not statistically significant ( P=0.741). The reconstructed tragus had a good three-dimensional structure and stable shape, and the simulated shape of the external auditory meatus was good. Patients can wear earphones to meet the needs of daily life. Conclusions:Using residual ear cartilage to reconstruct the tragus by flapping hinge-cartilage can improve the three-dimensional structure of the auricle and skin grafting to the concha cavity posterior to the tragus can simulate external auditory meatus. The reconstructed ear resembles the healthy one and meets the need of wearing earphones.