Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

Keloid is a common skin disease, and the mechanism of its occurrence is not fully understood. There is evidence to show that multiple factors such as genetics, race, age, gender, hormones, infection, immunity, and oxidative stress, etc. may be related to the occurrence of keloids. Metabolic remodeling and protein acylation modification, as two important biological processes, play important roles in various skin related diseases. Based on this, this article reviews the roles of metabolic remodeling and protein acylation modification in keloids and the interrelationship between the two biological processes, and explores the application prospects of targeting the two biological processes in the prevention and treatment of keloids.

In recent years, non-coding RNAs (ncRNAs) carried by exosomes have been shown to play an important regulatory role in multiple stages of wound healing. Exosomes can transport ncRNAs to different target cells or tissue and regulate the expression of target genes and downstream molecules. The proposed competing endogenous RNA (ceRNA) hypothesis suggests that RNAs can build a more sophisticated and complex gene regulatory network by competing for common response elements. Therefore, this review focuses on the long ncRNAs and circular RNAs carried by exosomes, discusses their regulatory roles as ceRNAs in the stages of inflammation, cell proliferation, and tissue remodeling in wound repair, respectively, and summarizes the feasibility of ncRNAs carried by exosomes as cell-free therapy, in order to provide a theoretical basis for clinical treatment of wounds.

Holistic integrative medicine(HIM), has been officially proposed since 2012. Its theoretical system has been continuously improved, and its practical methods have become increasingly diverse, becoming an inevitable choice and path for the medical development in the new era. This article demonstrates ten major propositions for HIM, elaborating on the connotation and extension of HIM from the perspectives of epistemology and methodology, in order to achieve the transformation and adaptive evolution of modern medicine.

Burn patients are at high risk for invasive fungal infections. The incidence of invasive fungal infection for burn victims is increasing dramatically during recent years and becoming one of the major causes of death in patients with severe burns. This updated guideline was initiated and organized by Burn Medicine Branch of China International Exchange and Promotion Association for Medical and Healthcare, and Editorial Committee of Chinese Journal of Burns and Wounds. Based on the current evidence-based medical evidence, clinical practice, and authoritative guidelines from other disciplines, we updated and revised the Guidelines for the diagnosis, prevention and treatment of invasive fungal infections post burn injury (2012 edition), aiming to further standardize the diagnosis, prevention and treatment of invasive fungal infection post burns.

Sepsis is the most common complication of severe burns and a primary risk factor for endangering the lives of critically severe burn patients. The mortality rate of burn sepsis patients was up to 75%. Neutrophils are one of the innate immune cells and are the earliest and most recruited immune cells at the site of infection, which play a key role in the removal of local infection and the repair of damaged tissue. Many studies have deeply revealed the pathogenesis and progression mechanism of burn sepsis, in which the role of neutrophils has gradually become clear. This paper elaborated on the key mechanisms of neutrophils in the occurrence and evolution of burn sepsis, explored the value of neutrophils in the early warning and prognosis judgement, and the potential therapeutic methods of burn sepsis based on the unique biological behavior of neutrophils in burn sepsis.

Objective:To explore the changes in entero-insular axis function and its role in mice with severe burns.Methods:This study was an experimental study. Ninety C57BL/6J male mice aged 8-10 weeks were divided into sham injury group and burn group (with 45 mice in each group) according to the random number table. A full-thickness scald (hereinafter referred to as burn) wound of 30% of the total body surface area was created on the back of mice in burn group, and the mice in sham injury group were simulated to cause a sham injury. Twenty-four hours after injury, the fasting blood glucose was measured ( n=12), followed by intraperitoneal glucose tolerance test and oral glucose tolerance test; the curve of blood glucose concentration changes over time was plotted, and the area under the curve was calculated ( n=6); the blood was taken from the heart before intraperitoneal injection or gavage of glucose solution and at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution for measuring the plasma insulin and glucagon like peptide-1 (GLP-1) levels using enzyme-linked immunosorbent assay (ELISA), with a sample number of 3; the ileal tissue was taken from 3 mice in each group for detecting the GLP-1 expression and apoptosis levels of intestinal L cells by immunofluorescence staining and TdT-mediated dUTP nick-end labeling staining; the pancreatic islets were collected from 6 mice in each group for glucose-stimulated insulin secretion experiments. After incubation with low glucose (2.8 mmol/L glucose) and high glucose (16.7 mmol/L glucose), the supernatant was taken and the insulin level was detected using ELISA. Thirty-six C57BL/6J male mice aged 8-10 weeks were divided into sham injury group, burn group, and burn+exendin-4 (Ex-4) group (with 12 mice in each group) according to the random number table. The mice in sham injury group and burn group were subjected to the same corresponding treatment as before. The mice in burn+Ex-4 group were injured in the same way as the burn group mice followed by treatment with GLP-1 receptor agonist Ex-4. Twenty-four hours after injury, mouse pancreatic islets were collected, the protein expressions of heavy-chain binding protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected using Western blotting, and the p-PERK/PERK and p-eIF2α/eIF2α ratios were calculated ( n=3), the apoptosis rate of pancreatic islet cells was detected using flow cytometry ( n=3), the glucose stimulated insulin secretion experiment was conducted as before to detect insulin levels in the supernatant ( n=6). Results:Twenty-four hours after injury, the fasting blood glucose of mice in burn group was (7.3±1.0) mmol/L, which was significantly higher than (5.1±0.6) mmol/L in sham injury group ( t=6.36, P<0.05). Twenty-four hours after injury, in the intraperitoneal glucose tolerance test and oral glucose tolerance test, the areas under the curve of blood glucose concentration changes over time of mice in burn group were significantly larger than those in sham injury group (with t values of 4.32 and 6.03, respectively, P<0.05); compared with those in sham injury group, the plasma insulin levels of mice before intraperitoneal injection of glucose solution and the plasma GLP-1 levels of mice before intraperitoneal injection or gavage of glucose solution in burn group were significantly decreased ( P<0.05), and the plasma levels of insulin of mice at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution, as well as the plasma levels of GLP-1 of mice at 30 and 60 minutes after gavage of glucose solution were significantly decreased in burn group ( P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the GLP-1 expression level of intestinal L cells of mice in burn group was significantly decreased ( t=7.74, P<0.05), and the apoptosis level was significantly increased ( t=14.28, P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was (8.5±0.4) ng/mg, which was significantly lower than (15.7±0.3) ng/mg in sham injury group ( t=18.68, P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn group were significantly increased ( P<0.05); compared with those in burn group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn+Ex-4 group were significantly decreased ( P<0.05). Twenty-four hours after injury, the apoptosis rate of pancreatic islet cells of mice in burn group was (32.0±3.0)%, which was significantly higher than (10.3±2.5)% in sham injury group ( P<0.05); the apoptosis rate of pancreatic islet cells of mice in burn+Ex-4 group was (20.0±3.6)%, which was significantly lower than that in burn group ( P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was significantly lower than that in sham injury group ( P<0.05), while the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn+Ex-4 group was significantly higher than that in burn group ( P<0.05). Conclusions:After severe burns, the mice display dysfunction of the entero-insular axis, increased apoptosis of intestinal L cells, decreased synthesis and secretion of GLP-1, endoplasmic reticulum stress and increased apoptosis in pancreatic islet cells and a decrease in glucose-stimulated insulin secretion. The GLP-1 receptor agonist Ex-4 can protect the function of pancreatic islet cells of mice with severe burns, reducing the apoptosis level of pancreatic islet cells and promoting insulin secretion possibly via the alleviation of endoplasmic reticulum stress.

Objective:To explore the changes in resting energy expenditure (REE) values in patients with severe burns under different metabolic stages and the selection of the optimal calculation formula.Methods:This study was a retrospective and observational study. From April 2020 to December 2023, 40 patients (32 males and 8 females, aged (54±17) years) with severe burns meeting inclusion criteria were treated in the Second Affiliated Hospital of Zhejiang University School of Medicine. After admission, the patients were given routine clinical treatments such as sedation and analgesia, debridement, and skin grafting. At 3, 5, 7, 9, 11, 14 days after injury and every 7 days thereafter, the REE values (i.e., REE measured values) were measured by indirect calorimetry in patients with severe burns who met the measurement conditions till the patients recovered or died. On the day the patient's REE was measured, Milner, Hangang, the Third Military Medical University, Carlson, and Peng Xi team's linear formula were used respectively to calculate the REE value (i.e., REE formula values). The post-injury time to measure REE in patients was calculated, and the clinical characteristics of patients in acute inhibition, hypermetabolic, metabolic balance, and metabolic remodeling phases were compared. The REE measured values and the difference between the REE formula values and the REE measured values of patients under the 4 different metabolic phases were calculated.Compared with the REE measured values, the 10% accuracy rate and 20% accuracy rate were calculated to evaluate the accuracy of the REE formula values. The absolute percentage error (APE) of the REE formula values were calculated to evaluate the deviation. The metabolic formula (i.e., the optimal calculation formula) that was closest to the measured REE values was screened out, and further exploration was conducted to identify the key factors that affected the accuracy of the optimal calculation formula under different metabolic phases.Results:The post-injury time to measure REE in patients with severe burns was (40±19) days. Comparisons showed that under the 4 different metabolic phases, patients in the metabolic remodeling phase had the highest age, height, weight, body mass index, total body surface area. Age in the metabolic remodeling phase was significantly higher than that in the acute inhibition and hypermetabolic phases (with t values of -3.02 and -4.20, respectively, with all P values <0.05), weight was significantly higher than that in the hypermetabolic and metabolic balance phases (with t values of -1.97 and -2.61, respectively, with all P values <0.05), body mass index was significantly higher than that in the hypermetabolic phase ( t=-2.90, P<0.05), and total body surface area was significantly larger than that in the hypermetabolic and metabolic balance phases (with t values of -2.02 and -2.27, respectively, with all P values <0.05). There was no significant change in patients' REE measured values under the 4 different metabolic stages ( P>0.05). Except for the Peng Xi team's linear formula ( P>0.05), the difference between REE measured values and REE formula values calculated by using Milner, Hangang, the Third Military Medical University, and Carlson formulas respectively was statistically significant under different metabolic stages (with H values of 14.50, 27.15, and 37.26, respectively, F=11.80, P<0.05). Comprehensive analysis of 10% accuracy, 20% accuracy, and APE showed that in the acute inhibition phase, the REE formula values calculated by Peng Xi team's linear formula was closest to REE measured values, and the APE of the REE formula values calculated by Peng Xi team's linear formula was significantly lower than those calculated by Milner formula, Hangang formula, the Third Military Medical University formula, and Carlson formula (with t values of 9.00, -2.10, 5.95, and 6.68, respectively, with all P values <0.05). In the hypermetabolic phase, the REE formula values calculated by Hangang formula were closest to REE measured values, with significantly lower APE of the REE formula values calculated by Hangang formula than those calculated by using Milner formula, the Third Military Medical University formula, Carlson formula, and Peng Xi team's linear formula (with t values of 10.20, 10.33, 10.65, and 5.87, respectively, with all P values <0.05). In the metabolic balance phase, the REE formula values calculated by Hangang formula were again closest to REE measured values, with significantly lower APE of the REE formula values calculated by Hangang formula than those calculated by Milner formula, the Third Military Medical University formula, and Carlson formula (with t values of 7.11, 8.52, and 8.60, respectively, with all P values <0.05). In the metabolic remodeling phase, the REE formula values calculated by the Third Military Medical University were closest to REE measured values, with significantly lower APE of the REE formula values calculated by the Third Military Medical University formula than those calculated by Milner formula, Hangang formula, and Carlson formula (with t values of 5.12, 2.45, and 6.26, respectively, with all P values <0.05). No significant key factors affected the accuracy of the Peng Xi team's linear formula in the acute inhibition phase ( P>0.05). In the hypermetabolic phase, total burn area was a key factor affecting the accuracy of Hangang formula (with odds ratio of 1.00, with 95% confidence interval of 1.00-1.10, P<0.05). In the metabolic balance phase, post-injury days was a key factor affecting the accuracy of Hangang formula (with odds ratio of 1.30, with 95% confidence interval of 1.10-1.40, P<0.05). In the metabolic remodeling phase, no significant key factors affected the accuracy of the Third Military Medical University formula ( P>0.05). Conclusions:When calculating REE values in patients with severe burns, it is recommended to use the Peng Xi team's linear formula during the acute inhibition phase, the Hangang formula during the hypermetabolic and metabolic balance phases, and the Third Military Medical University formula during the metabolic remodeling phase. Additionally, it is crucial to ensure the accuracy of key factors affecting the optimal calculation formula in the hypermetabolic and metabolic balance phases.

Objective:To explore the clinical effects of chimeric perforator flaps in repairing wounds with bone or internal fixation exposure and wounds with osteomyelitis.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 20 patients with wounds with bone or internal fixation exposure and wounds with osteomyelitis who met the inclusion criteria were admitted to Beijing Jishuitan Hospital Affiliated to Capital Medical University, including 19 males and 1 female, aged from 21 to 73 years. Among the 21 wounds, there were 5 wounds with bone exposure, 12 wounds with osteomyelitis, and 4 wounds with internal fixation exposure. After the debridement in the first stage, the wound area was 6 cm×3 cm to 22 cm×10 cm. Then vacuum sealing drainage was carried out for 5 to 7 days. In the second stage, the wounds were covered with pedicled chimeric medial sural artery perforator flap, pedicled chimeric posterior tibialis artery perforator flap, free chimeric perforator flap pedicled with descending branch of lateral circumflex femoral artery, free chimeric medial sural artery perforator flap or free chimeric deep circumflex iliac artery perforator flap with incision area of 7 cm×5 cm to 25 cm×12 cm. The chimeric muscle flap was used to fill and cover irregular deep cavities. The wounds in the flap donor sites were sutured directly or repaired with medium-thickness skin grafts from the thigh. The survival of flap and the healing of wound in flap donor site were observed after operation. The recurrence of infection was followed up.Results:Among the 18 free chimeric perforator flaps, 16 flaps survived successfully; one flap experienced a venous crisis on the day of surgery and survived completely after emergency exploration and re-anastomosis; another one flap had partial distal necrosis, which healed after dressing changes. All the wounds in the flap donor sites healed evenly. All 3 pedicled chimeric perforator flaps survived; one of them developed sub-flap infection but healed after debridement and bone cement placement. The wound in the donor site of 1 flap developed incision dehiscence, which healed successfully after redebridement and suturing. The donor site wounds of the rest 2 flaps healed well. During 3 to 12 months of follow-up, the patients with wounds with bone or internal fixation exposure showed no signs of abnormal exudation or infection, and no infection recurrence was observed in patients with wounds with osteomyelitis.Conclusions:The application of chimeric perforator flaps is effective in covering wounds, filling dead spaces, and controlling infection in wounds with bone or internal fixation exposure and wounds with osteomyelitis. Moreover, this method minimizes the damage to the donor site.

Objective:To investigate the clinical effects of combined tissue flap transplantation in repairing giant chest wall defects.Methods:This study was a retrospective observational study. From August 2013 to December 2020, 31 patients with chest wall tumor or radiation ulcer after radical resection of chest wall tumor and conformed to the inclusion criteria were admitted to the Department of Breast Oncoplastic Surgery of Hunan Cancer Hospital, including 12 males and 19 females, aged 25-71 years. After resection of tumor or ulcer and wound debridement, the area of secondary chest wall defect was 300-600 cm 2 with length of 16-35 cm and width of 16-32 cm. According to the actual situation of the patients and the preoperative design, the chest wall defects were repaired with the flexible combination of perforator flaps and myocutaneous flaps from different donor sites, and the area of the combined tissue flap was 260-540 cm 2 with length of 20-30 cm and width of 13-20 cm. Free posteromedial thigh perforator flap+free anterolateral thigh myocutaneous flap were used in 2 patients, free deep inferior epigastric artery perforator flap+free anterolateral thigh myocutaneous flap were used in 5 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+free anterolateral thigh myocutaneous flap were used in 7 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+pedicled latissimus dorsi myocutaneous flap were used in 2 patients, and bilateral free anterolateral thigh myocutaneous flaps were used in 15 patients. For the remaining small area of superficial tissue defect after being repaired by combined tissue flaps, skin graft was used to repair or delayed local flap transfering was performed after the tissue flaps survived and edema subsided. The appropriate blood vessels in the donor and recipient sites were selected for anastomosis to reconstruct the blood supply of tissue flaps. The wounds in the donor sites of tissue flaps that can be directly sutured were sutured directly; for those that cannot be sutured directly, the skin grafting or delayed suture was performed. The anastomosis of blood vessels in the recipient sites, operation length, and postoperative hospital stay were recorded. The survivals of tissue flaps and skin grafts, the shape and texture of reconstructed chest wall, the wound healing, scar formation, and function of donor sites of tissue flaps, and the scar formation of the donor sites of skin grafts were observed after operation. Tumor recurrence and death of recurrent patients were followed up after operation. Results:The blood vessels in the recipient sites were anastomosed as follows: proximal internal thoracic vessels for 24 times, distal internal thoracic vessels for 12 times, trunk of thoracodorsal vessels for 4 times, anterior serratus branches of thoracodorsal vessels for 8 times, and thoracoacromial vessels for 12 times. The operation length was 6.0 to 8.5 hours, and the postoperative hospital stay was 9 to 21 days. Necrosis at the edge of partial tissue flaps occurred in 4 patients after operation, which healed after dressing change, and the tissue flaps and skin grafts of the other patients survived completely. The shape and texture of the reconstructed chest wall were good. Four patients had poor wound healing in the donor sites of abdominal tissue flaps, which healed after dressing change and local drainage. Only linear scar was left in the donor sites of all tissue flaps, and there was no obvious dysfunction in the donor sites of tissue flaps. Mild hypertrophic scar was left in the donor sites of skin grafts. During follow-up of 9 to 36 months after operation, 6 patients had tumor recurrence, and the recurrence time was 5 to 20 months after operation. After comprehensive treatment for patients with tumor recurrence, 3 patients died.Conclusions:Transplantation of combined tissue flaps in repairing the giant chest wall defects can shorten the time of total operation and hospital stay, and avoid multiple operations. After operation, patients had good chest wall appearance, with reduced tumor recurrence in patients with chest wall tumor.