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.

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 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 investigate the protective effect of Honokiol on the airway inflammation induced by particulate matter 2.5(PM2.5)in the asthmatic mice and its mechanism.Methods Fifty male specific pathogen free (SPF)Balb/c mice were randomly divided into 5 groups.Group A:normal control group;group B:asthmatic model group;group C:PM2.5 exposure asthmatic group;group D:TAK -242 group;group E:Honokiol group. Asthmatic mouse models were established by ovalbumin(OVA)sensitization and challenge.On days 0 and 7,the mice in B-E groups were injected intraperitoneally with injection 100 mg/L OVA and aluminum hydroxide for sensitization;on days 14 to 21,10 g/L OVA solution was given 30 min per day to challenge.During challenge phrase,the mice in C -E groups received intratracheal injection of PM2.5,every other day,4 times totally.On this basis,the mice in group D re-ceived TAK-242 intraperitoneal injection,and the mice in group E received honokiol intragastric administration.Group A was given saline instead of OVA.Animals were sacrificed 24 h after the final inhalation challenge,and the bronchoal-veolar lavage fluid(BALF)of the left lung was used for differential inflammatory cell counts.The expressions of Toll-like receptors 4(TLR4)and nuclear factor(NF)-κB at mRNA level were detected by real-time quantitative PCR. Flow cytometry analysis was performed to measure the levels of Th17 and Treg cells.Results Compared with group A,mice in group B and group C expressed more serious disorders of bronchial epithelial cells,alveolar wall congestion and edema,increased mucus secretion in the airway and infiltration of inflammatory cells in the lung,and those in group C were more obvious than those of group B and group E significantly reduced respiratory inflammation;compared with group A[(4.15 ± 1.35)×108/L,0.012 0 ± 0.002 3],the total number of inflammatory cell counts[(16.79 ± 5.62)×108/L and(24.58 ± 13.46)×108/L],eosinophils proportions(0.113 8 ± 0.022 3 and 0.197 8 ± 0.084 9)in group B and group C,were significantly higher,and the differences were statistically significant(all P<0.05);The total number of inflammatory cell counts and eosinophils proportion in group E(8.56 ± 3.28)×108/L and 0.041 5 ± 0.013 5)were significantly lower than those in group C,and the differences were statistically significant(all P <0.05);The expressions of TLR4 mRNA and NF-κB mRNA in group B and C(1.85 ± 0.56,1.82 ± 0.28 and 2.97 ± 0.41,2.83 ± 0.32)were significantly higher,and the differences were statistically significant(all P <0.05);The expressions of TLR4 mRNA and NF-κB mRNA in group E(1.60 ± 0.28,1.54 ± 0.25)was significantly lower than those in group C,and the differences were statistically significant(all P<0.05);the expressions of Th17 in group B and C[(2.89 ± 0.61)% and(4.96 ± 0.27)%]were significantly higher than those of group A[(1.03 ± 0.35)%] (all P<0.05);The expression of Th17 in group E[(1.83 ± 0.23)%]was significantly lower than that of group C,and the differences were statistically significant(P<0.05);the expressions of Treg in group B and C[(4.96 ± 0.35)%and(2.27 ± 0.41)%]were significantly lower than those of group A[(7.37 ± 0.56)%],and the differences were sta-tistically significant(all P<0.05);The expression of Treg in group E was significantly increased[(6.45 ± 0.38)%] compared with that in group C,and the difference were statistically significant(P<0.05);and those of group D and E were improved remarkably.Conclusions Honokiol can relieve PM2.5 exposure of asthmatic airway inflammation through down-regulating the expression of TLR4 and NF-κB and Th17 and regulating the balance of Th17 and Treg cells.

Objective To investigate the anti-inflammatory and immunosuppressive effects of honokiol in a mouse model of particulate matter ( PM ) 2.5-induced asthma .Methods Female SPF BALB/c mice were randomly divided into five groups:normal saline group (group A), ovalbumin (OVA)-sensitized group ( group B), PM2.5-exposed+OVA-sensitized group ( group C), dexamethasone-treated group (group D) and honokiol-treated group (group E).All mice except those in group A were sensitized and challenged with OVA, and the mice in groups C, D and E were exposed to PM2.5 every two days since the first challenge.Samples of lung sections were stained with hematoxylin and eosin (HE) to observe in-flammatory infiltration.Bronchoalveolar lavage fluid (BALF) and PBMCs were collected from each mouse . Expression of RORγt and Foxp3 at mRNA level was detected by quantitative real-time PCR.Flow cytometry analysis was performed to measure the percentages of Th 17 and Treg cells.ELISA was performed to measure the levels of IFN-γ, IL-10 and IL-17 in the supernatants of cell culture .Results Compared with group B , group C showed an enhanced expression of RORγt at mRNA level, increased IL-17 level and up-regulated percentage of Th17 cells (all P<0.05), but a suppressed expression of Foxp3 at mRNA level, decreased IL-10 level and down-regulated percentage of Th17 cells (all P<0.05).No significant difference in the per-centage of Th1 cells or in the expression of Th 1-related cytokines was observed .The expression of RORγt at mRNA level, IL-17 level and the percentage of Th 17 cells were decreased in PM2.5-exposed mice upon honokiol intervention (all P<0.05), while the expression of Foxp3 at mRNA level, IL-10 level and the per-centage of Treg cells were increased after honokiol intervention (all P<0.05).Honokiol had similar efficacy to dexamethasone in the treatment of asthma .Conclusion Honokiol can alleviate airway inflammation in mice with PM2.5 exposure-induced asthma through regulating the percentages of Th 17 and Treg cells.

Objective To explore the children and their family's specialties in attention-deficit hyperactivity disorder(ADHD).Method 60 cases of ADHD was diagnosed by employing ADHD Behavior Screen with DSM-IV .The control group was confirmed according to 1:1age and sex matched case control study design, then all children were surveyed themselves and family neuropsytric condition with questionnaire, Analyzed data with SAS6 12 statistics software.Results Children and family neuro-psytric surveying questionnaire showed that there were significant difference in partial or particular diet, habit of biting nail, family anamnesis, relation of parents, relation of parent-child, attitude of parents, uprearing mode of parents, characteristics of parents. Logistic elimination regression analysis indicated that partial-meal , biting-nail, mother's non-vivacious character and bad parental relation were the significant risk factors.Conclusion The bad habit of children and wrong family surrounding will promote occurrence of ADHD. Rectifing children's habits , changing mother's cyclothymia and cultivating good relation of father,doing so,the son might decrease incidence of ADHD.