Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

Objective:To explore the clinical effects of flaps or myocutaneous flaps transplantation after debridement to repair the wounds with exposed titanium mesh after cranioplasty on the premise of retaining the titanium mesh.Methods:This study was a retrospective observational study. From February 2017 to October 2022, 22 patients with titanium mesh exposure after cranioplasty who met the inclusion criteria were admitted to the Department of Plastic, Aesthetic & Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University, including 15 males and 7 females, aged from 19 to 68 years. After admission, treatments such as bacterial culture of wound exudate sample, anti-infection, and dressing change were carried out. Thorough surgical debridement was performed when the wound improved, and the wound area was 3.0 cm×2.0 cm to 11.0 cm×8.0 cm after debridement. The wound was repaired with local flaps, expanded flaps, or free latissimus dorsi myocutaneous flaps according to the size, location, severity of infection, and surrounding tissue condition of the wounds, and the areas of flaps or myocutaneous flaps were 5.5 cm×4.0 cm to 18.0 cm×15.0 cm. The donor areas of flaps were sutured directly or repaired by split-thickness skin grafts from head. The wound repair method was recorded. The survivals of flaps or myocutaneous flaps after surgery and wound healing in 2 weeks after surgery were recorded. During postoperative follow-up, recurrence of infection or titanium mesh exposure in the implanted area of titanium mesh was observed; the head shapes of patients, scar formation of the operative incision, and baldness were observed. At the last follow-up, the satisfaction of patients with the treatment effect (dividing into three levels: satisfied, basically satisfied, and dissatisfied) was evaluated. The total treatment costs of patients during their hospitalization were calculated.Results:The wounds in 11 cases were repaired with local flaps, the wounds in 5 cases were repaired with expanded flaps, and the wounds in 6 cases were repaired with free latissimus dorsi myocutaneous flaps. All flaps or myocutaneous flaps survived completely after surgery, and all wounds healed well in 2 weeks after surgery. Follow up for 6 to 48 months after operation, only one patient with local flap grafting experienced a recurrence of infection in the titanium mesh implanted area at more than one month after surgery, and the titanium mesh was removed because of ineffective treatment. Except for one patient who had a local depression in the head after removing the titanium mesh, the rest of the patients had a full head shape. Except for myocutaneous flap grafting areas in 6 cases and skin grafting area in 1 case with local flaps grafting had no hair growth, the other patients had no baldness. All the scars in surgical incision were concealed. At the last follow-up, 19 cases were satisfied with the treatment effects, 2 cases were basically satisfied, and 1 case was dissatisfied. The total treatment cost for patients in this group during hospitalization was 11 764-36 452 (22 304±6 955) yuan.Conclusions:For patients with titanium mesh exposure after cranioplasty, on the premise of adequate preoperative preparation and thorough debridement, the wound can be repaired with appropriate flaps or myocutaneous flaps according to the wound condition. The surgery can preserve all or part of the titanium mesh. The postoperative wound healing is good and the recurrence of infection or titanium mesh exposure in the titanium mesh implanted area is reduced, leading to good head shape, reduced surgical frequency, and decreased treatment costs.

Objective:To investigate the clinical effect of repairing unilateral incomplete cleft lip functionally and sub-regionally with modified micro-triangular skin flap and orbicularis oris muscle flaps.Methods:A retrospective study was conducted in the patients with unilateral incomplete cleft lip, who underwent repair at Department of Plastic, Aesthetic and Maxillofacial Surgery, the First Affiliated Hospital of Xi’an Jiaotong University from April 2020 to February 2023. Surgical landmarks were fixed according to the anatomical structure of non-cleft side. Short straight skin incisions were designed along the philtral column. A micro-triangular flap was designed above the vermilion margin of the affected lip, which was inserted into the contralateral lip peak to lower the lip peak and lengthen the philtral column. The orbicularis oris muscle was reconstructed with five muscle flaps in three areas to create a good sub-structure of the upper lip and the nasal floor. The vermilion tubercle and philtral column were reconstructed. Deviation of nasal columella was corrected and the nasal floor was elevated. The outcomes were assessed through subjective evaluation and objective anthropometric measurements.(1) Subjective outcomes were assessed by two plastic surgeons together who were not included in this study. The following parameters were assessed: scar appearance, Cupid’s bow continuity, lip pick height, alar base width, nostril symmetry, philtral ridge contour. Each parameter was graded from 1 point (poor), 2 points (average), or 3 points (good). (2) Objective measurements were taken by one plastic surgeon who was not included in this study using the Image-Pro Plus 6.0. Measurements were included bilateral vermilion thickness, bilateral length of lip pick to cheilion, bilateral philtral column length, bilateral length of Cupid’s pick to ala nasi, bilateral alar base width. Asymmetry ratio = |non-cleft counts-cleft counts|/non-cleft counts×100%, and a value closer to 0 would mean the less different, the more symmetrical. Statistical analysis was performed using descriptive methods. Non-normal distributed measurement datas were expressed by M( Q1, Q3). Results:A total of 32 patients of unilateral incomplete cleft lip were enrolled, including 19 males and 13 females, aged 3-18 months. All patients were primary healing, and no serious complications (i.e., infection, hematoma, wound dehiscence) occurred. The postoperative follow-up time was 6-24 months. The patients were satisfied with the results, including favorable red lip contour, good continuity, obvious vermilion, cubical philtrum column, good symmetry of bilateral structure and sub-structure and light scar. The overall score of the subjective evaluation was 2.66 points. Cupid’s bow continuity got the highest score(2.84 points), and nostril symmetry got the lowest score(2.38 points). Objective measurements indicated excellent parameters were bilateral alar base width [2.60%(1.02%, 7.08%)] and bilateral philtral length[3.95%(2.03%, 5.98%)].Conclusion:Repairing unilateral incomplete cleft lip functionally and sub-regionally with modified micro-triangular skin flap and orbicularis oris muscle flaps can create a good sub-structure of the upper lip contour, and bring a significant improvement in the upper lip and the nasal floor symmetry, which is an effective method for incomplete unilateral cleft lip repair.

Objective:To investigate the clinical effect of repairing unilateral incomplete cleft lip functionally and sub-regionally with modified micro-triangular skin flap and orbicularis oris muscle flaps.Methods:A retrospective study was conducted in the patients with unilateral incomplete cleft lip, who underwent repair at Department of Plastic, Aesthetic and Maxillofacial Surgery, the First Affiliated Hospital of Xi’an Jiaotong University from April 2020 to February 2023. Surgical landmarks were fixed according to the anatomical structure of non-cleft side. Short straight skin incisions were designed along the philtral column. A micro-triangular flap was designed above the vermilion margin of the affected lip, which was inserted into the contralateral lip peak to lower the lip peak and lengthen the philtral column. The orbicularis oris muscle was reconstructed with five muscle flaps in three areas to create a good sub-structure of the upper lip and the nasal floor. The vermilion tubercle and philtral column were reconstructed. Deviation of nasal columella was corrected and the nasal floor was elevated. The outcomes were assessed through subjective evaluation and objective anthropometric measurements.(1) Subjective outcomes were assessed by two plastic surgeons together who were not included in this study. The following parameters were assessed: scar appearance, Cupid’s bow continuity, lip pick height, alar base width, nostril symmetry, philtral ridge contour. Each parameter was graded from 1 point (poor), 2 points (average), or 3 points (good). (2) Objective measurements were taken by one plastic surgeon who was not included in this study using the Image-Pro Plus 6.0. Measurements were included bilateral vermilion thickness, bilateral length of lip pick to cheilion, bilateral philtral column length, bilateral length of Cupid’s pick to ala nasi, bilateral alar base width. Asymmetry ratio = |non-cleft counts-cleft counts|/non-cleft counts×100%, and a value closer to 0 would mean the less different, the more symmetrical. Statistical analysis was performed using descriptive methods. Non-normal distributed measurement datas were expressed by M( Q1, Q3). Results:A total of 32 patients of unilateral incomplete cleft lip were enrolled, including 19 males and 13 females, aged 3-18 months. All patients were primary healing, and no serious complications (i.e., infection, hematoma, wound dehiscence) occurred. The postoperative follow-up time was 6-24 months. The patients were satisfied with the results, including favorable red lip contour, good continuity, obvious vermilion, cubical philtrum column, good symmetry of bilateral structure and sub-structure and light scar. The overall score of the subjective evaluation was 2.66 points. Cupid’s bow continuity got the highest score(2.84 points), and nostril symmetry got the lowest score(2.38 points). Objective measurements indicated excellent parameters were bilateral alar base width [2.60%(1.02%, 7.08%)] and bilateral philtral length[3.95%(2.03%, 5.98%)].Conclusion:Repairing unilateral incomplete cleft lip functionally and sub-regionally with modified micro-triangular skin flap and orbicularis oris muscle flaps can create a good sub-structure of the upper lip contour, and bring a significant improvement in the upper lip and the nasal floor symmetry, which is an effective method for incomplete unilateral cleft lip repair.

Objective:To explore the clinical effects of free pre-expanded deltopectoral flap transfer in facial scar reconstruction by selecting appropriate internal thoracic artery perforator as the pedicle through preoperative color Doppler ultrasonic vascular assessment.Methods:A retrospective observational study was conducted. From September 2017 to March 2021, 11 patients with facial scar who met the inclusion criteria were admitted to the First Affiliated Hospital of Xi'an Jiaotong University, including 6 males and 5 females, aged 16-58 (31±12) years. The scar with area ranging from 7 cm×5 cm to 14 cm×9 cm was reconstructed by free pre-expanded internal thoracic artery perforator pedicled deltopectoral flap transfer. The operation was performed in 2 or 3 stages. Before operation, color Doppler ultrasonography was performed to evaluate the internal thoracic artery perforator. In the first stage, skin and soft tissue expander (hereinafter referred to as expander) implantation was performed, and a cylindrical expander with rated capacity of 400 to 600 mL was placed in the chest wall. The expansion time was 3 to 4 months, and the water injection volume reached 1.2-1.5 times of the rated capacity of expander. In the second stage, scar excision+free pre-expanded deltopectoral flap transfer was performed, with harvested flap area ranging from 9 cm×7 cm to 16 cm×10 cm. The vascular pedicle of flap (intercostal perforator of internal thoracic artery) was anastomosed end-to-end to the facial artery and vein or superficial temporal artery and vein. The wound in donor site was closed directly. Third stage operation thinning was performed at 3-6 months after the second stage operation in 5 patients because of bloated flap pedicle. At 6 months after the last operation, the flap survival and complications were recorded, the sensation of flap was evaluated by Semmes-Weinstein monofilament test, the color of flap was evaluated by color contrast of the flap to surrounding normal skin, and the curative effect satisfaction degree of patients was evaluated by 5-grade Likert scale.Results:At 6 months after the last operation, all the flaps of 11 patients survived well. One patient experienced venous congestion after flap transplantation, but the flap survived after re-anastomosis. One patient experienced hematoma after the first stage operation of expander implantation, but the rest treatment was not influenced after hematoma removal. No complications such as infection or expander exposure occurred in any patient. At 6 months after the last operation, the sensation of flap of patient was as follows: 9 cases recovered to protective sensation decrease or better, 1 case had protective sensation defect, and 1 case only had deep touch and pressure sensation; the color of flap of patient was as follows: 3 cases were very close to the color of surrounding normal skin, 6 cases were close to the color of surrounding normal skin, and 2 cases were different to the color of surrounding normal skin; the curative effect satisfaction degree of patients was as follows: 2 patients were very satisfied, 6 patients were satisfied, 2 patients were somewhat satisfied, and 1 patient was a little not satisfied.Conclusions:The large area facial scar can be treated safely and effectively by free pre-expanded deltopectoral flap with appropriate single internal thoracic artery perforator as vascular pedicle selected through vascular assessment by color Doppler ultrasonography before operation. After operation, the color of flap of patients is close to the surrounding normal skin and the sensation of flap can be partially recovered, with high curative effect satisfaction degree of patients.

Objective:To investigate the clinical effect of postauricular island flap in reconstruction of anterior auricular defect.Methods:Twelve patients with auricular tumors were retrospectively analyzed in the Department of Aesthetic Plastic and Craniofacial Surgery, the First Affiliated Hospital of Xi'an Jiaotong University. After the tumors were completely removed, the skin defects were repaired with retroauricular island flaps, and the clinical results of the flaps were observed.Results:All the twelve postauricular island flaps were survived postoperatively. One of the flaps had the disorder of blood supply. After puncture with the needle, the congestion was drained out and the flap survived finally. During 1 to 2 years' follow-up, all patients were well satisfied with the surgical results.Conclusions:The posterior auricular island flap in reconstruction of anterior auricular defect has the advantages of simple and easy operation, high survival rate, small scar in the donor area and good aesthetic effect, which is worthy of clinical promotion.

Objective To explore the effectiveness of the individualized surgical fixation for the treatment of mandibular fractures in children.Methods The individualized mandibular fixation methods were used to treat mandibular fractures in 85 children in Department of Plastic and Reconstructive Surgery in Xijing Hospital from April 2010 to July 2015.Depending on the fracture types and 3D pre simulation with stress and tension band fixation,six methods of treatment were used,including titanium plate,titanium plate-dental arch bars,biodegradable plate-dentalarch bars,biodegradable plate-occlusal splint,occlusal splint,and anchorage devices.Postoperative occlusal relationship,mouth opening and masticatory function were evaluated.Results Fixation of titanium plate was used in 10 cases,titanium plate-dental arch bars in 25 cases,biodegradable plate-dentalarch bars in 20 cases,biodegradable plate-occlusal splint 15 cases,individualized occlusal splint in 3 cases and anchorage devices in 12 cases.The treatment outcomes were good in the combined methods of open reduction with personalized fixation for children with mandibular fractures,and the reduction was satisfactory.Occlusal relationship had a good recovery after operation.Eating and functional training started earlier in these pediatric patients after operation.Conclusions For pediatric mandibular fractures,open reduction and fixation with appropriate methods can lead to favorable anatomic morphology and occlusion relationship.The application of 3D imaging technology in analyzing the fracture and showing tooth germ in the jaw helps the improvement of surgical efficiency and avoidance of unwanted tooth germ injuries.Personalized dental arch bar and splint provide good strength for external fixation or assist fixation on strain band.