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2024 Vol. 40, No. 6

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Expert Forum
Diagnosis and treatment strategies of chronic radiation ulcers
Shen Yuming, Hu Yungang
2024, 40(6): 501-506. doi: 10.3760/cma.j.cn501225-20240308-00091
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With the increase of radiotherapy and various interventional therapies for tumor, the number of patients with chronic radiation ulcers is increasing gradually. Chronic radiation ulcers mostly involve the deep subcutaneous layers, accompanied by fibrosis of the surrounding skin. The ulcers persist and develop progressively and irreversibly. It is difficult to achieve good curative effects by routine dressing change and skin grafting, seriously affecting the patients' quality of life. This article systematically discusses the pathogenesis, clinical characteristics, pathological changes, wound assessment, and repair strategies of chronic radiation ulcers to provide a reference for the clinical diagnosis and treatment of chronic radiation ulcers.
Roles of hypoxia and inflammation in wound healing
Wei Zairong, Zhang Yanji, Wang Dali
2024, 40(6): 507-513. doi: 10.3760/cma.j.cn501225-20240111-00014
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Wound healing is a complex biological process. Hypoxia and inflammation are the two key factors that initiate wound healing and affect the wound healing process. Hypoxia-inducible factor-1α (HIF-1α) and nuclear factor κB are the important regulators of hypoxia and inflammation. The interaction between hypoxia and inflammation is essentially mediated by HIF-1α and nuclear factor κB signaling pathways. The abnormal expression of HIF-1α or nuclear factor κB signaling pathway caused by the imbalance of hypoxia and inflammation will affect the wound microenvironment and lead to abnormal wound healing. This paper discussed the effects of hypoxia and inflammation on wound healing, emphasized the role of cooperation between hypoxia and inflammation on wound healing and the effect of their imbalance on the quality of wound healing, summarized the current intervention strategies of hypoxia and inflammation signaling pathways, and prospected the treatment of wound in the future.
Transcriptomic research on severe burns: value and prospects
Jia Chiyu, Yin Bin, Zhang Zexin
2024, 40(6): 514-520. doi: 10.3760/cma.j.cn501225-20231026-00135
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Transcriptomics technology has shown remarkable application effects in multiple disease fields, but its application in severe burns, especially in the field of burn sepsis, is still superficial. The use of transcriptomics and big data methods to solve the long-standing challenges of severe burns, especially in the field of burn sepsis, has great prospects and significance. This article comprehensively discusses the application value, current status, and future prospects of transcriptomics in the study of severe burns, especially burn sepsis, in order to provide new ideas for the treatment of severe burns.
Original Article·Refractory Wound Repair
Repair strategy of chest radiation ulcer after radical mastectomy for breast cancer and its clinical effect
Du Weili, Shen Yuming, Cheng Lin, Dai Qiang, Che Kexin
2024, 40(6): 521-528. doi: 10.3760/cma.j.cn501225-20240315-00099
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  Objective  To explore the repair strategy of chest radiation ulcer after radical mastectomy for breast cancer and its clinical effect.  Methods  The study was a retrospective observational study. From September 2020 to September 2023, 27 female patients (aged 37-83 years) with chest radiation ulcers after radical mastectomy for breast cancer who met the inclusion criteria were admitted to Beijing Jishuitan Hospital Affiliated to Capital Medical University, of which 7 patients developed significant pain in the chest region. Various examinations were completed to accurately assess the presence of tumors and depth of radiation ulcers. After tumor recurrence was ruled out, the ulcer wounds were thoroughly debrided (the wound size after debridement was 8 cm×7 cm to 18 cm×18 cm). At the same time, pathological examination of the wound tissue and bacterial culture of the wound tissue/exudate samples were performed. The wound repair surgery was performed at the same time after debridement or one week after vacuum sealing drainage (VSD) treatment. Based on the location and size of the wound, the age and overall condition of the patient, as well as the principle of minimizing damage to the donor site, the most suitable tissue flap was selected to repair the wound. The donor site wound was transplanted with a split-thickness skin graft or sutured together. The level and tissue structure of radiation injury, and the type and size of transplanted tissue flap were recorded. The results of postoperative pathological examination of wound tissue and bacterial culture of wound tissue/exudate samples, pain relief, survival of tissue flap, and wound healing were recorded. During the follow-up, the shape of the tissue flap, whether the ulcer recurred, the wound healing of the donor site, and whether the abdominal wall hernia occurred in the donor site of the rectus abdominis myocutaneous flap were observed.  Results  Radiation injury involved ribs and costal cartilage in 21 cases, ribs, sternum, and clavicle in 4 cases, and clavicle and subclavian artery in 2 cases. Twelve patients were transplanted with rectus abdominis myocutaneous flap, eight patients with latissimus dorsi myocutaneous flap, three patients with internal thoracic artery perforator flap, three patients with superior epigastric artery perforator flap, and one patient with free deep inferior epigastric perforator flap. The size of tissue flap was 14 cm×8 cm to 20 cm×20 cm. After surgery, no tumor component was found in the pathological examination of wound tissue; 25 patients were positive and 2 patients were negative in bacterial culture results of wound tissue/exudate samples; the pain of 7 patients was completely relieved. The tissue flaps of 25 patients survived completely after surgery, and the wounds healed. Two patients had partial necrosis at the tip of the rectus abdominis myocutaneous flap, which healed after debridement and tissue flap repair. The patients were followed up for 6 months to 2 years. The appearance of the tissue flaps was good, and no ulcer recurred. The linear scar was left on the donor site, and no abdominal wall hernia occurred in the donor site of the rectus abdominis myocutaneous flap.  Conclusions  Thorough debridement and VSD treatment after accurate assessment of the extent of damage, and the selection of appropriate tissue flap to repair the wound based on the patient's general condition, the wound characteristics, and the principle of minimizing damage to the donor site are good repair strategies for the chest radiation ulcers after radical mastectomy for breast cancer. By using the strategies, the wounds could be closed as soon as possible, preventing ulcer recurrence and having a good prognosis.
Repair methods and effects of refractory wounds in patients after spinal internal fixation operation
Li Lili, Yu Wenchang, Li Bo, Wu Deyong, Wang Jinyong, Zou Xiaohui, Wang Mingzhu, Xu Xiangrong
2024, 40(6): 529-535. doi: 10.3760/cma.j.cn501225-20240218-00066
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  Objective  To explore the repair methods and effects of refractory wounds in patients after spinal internal fixation operation .   Methods  The study was a retrospective observational study. From November 2020 to October 2023, 10 patients with refractory wounds after spinal internal fixation operation were admitted to the Department of Burns and Plastic Surgery of Changde Hospital of Xiangya School of Medicine of Central South University. They were 3 males and 7 females, aged 35 to 68 years. There were 6 cases of thoracolumbar tuberculosis, 3 cases of thoracolumbar fracture, and 1 case of recurrent sacrococcygeal chordoma with skin, soft tissue, and bone defects after radical resection. The wound areas after debridement were 6.0 cm×1.5 cm to 27.0 cm×6.5 cm. The wound repair operation was decided to perform in the primary stage or in the secondary stage according to the wound situation. Two patients with type Ⅰ wounds were treated with debridement, direct suture, and continuous irrigation and drainage with catheter after operation. Eight patients with type Ⅱ wounds were repaired with local flaps (including rotation flap with dermis-fat flap at the end), muscle flaps, or muscle flaps combined with local flaps. The flap sizes were 10.0 cm×5.0 cm to 27.0 cm×14.0 cm, and the sizes of muscle flap were 8.0 cm×5.0 cm×4.0 cm to 17.0 cm×9.5 cm×2.0 cm. The wounds in flap donor areas were sutured directly. The wound treatment methods of patients with type Ⅱ wounds were recorded. The wound healing was observed after operation. The infection and recurrence of wounds, the retention of internal fixation materials, and spinal motor function were observed during follow-up.  Results  Among patients with type Ⅱ wounds, there were 3 cases applied with local flaps (including 1 case with rotation flap with dermis-fat flap at the end), 3 cases with muscle flaps (including 1 case with latissimus dorsi muscle flap and 2 cases with erector spinal muscle flaps), and 2 cases with muscle flaps (1 case with latissimus dorsi muscle flap and 1 case with erector spinal muscle flap) combined with local flaps. Only 1 case with secondary defects after radical surgery of sacrococcygeal chordoma had poor wound healing which healed after dressing change, and the wounds of the remaining 9 cases all healed well. During the follow-up of 4 to 18 months, no infection or recurrence of local wounds developed in 10 patients, the internal fixation materials were not loosening, and there was no significant limitation in spinal motor function.  Conclusions  For refractory wounds after spinal internal fixation operation, according to the wound type of patients, debridement, suture, irrigation, and drainage in the primary stage, or transplantation of local flaps, muscle flaps, muscle flaps combined with local flaps are performed in the primary stage or in the secondary stage. These methods are proved to have reliable therapeutic effects, not only repairing the wounds, but also retaining the internal fixation materials.
Diagnosis and treatment strategy of complex post-sternotomy mediastinitis with exposure of artificial implants
Xie Kun, Zhang Zhengkui, Wen Bing
2024, 40(6): 536-542. doi: 10.3760/cma.j.cn501225-20240227-00074-0515
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  Objective  To explore the diagnosis and treatment strategy of complex post-sternotomy mediastinitis with exposure of artificial implants (hereinafter referred to as implants).  Methods  This study was a retrospective observational study. From January 2016 to January 2023, 16 patients with complex mediastinal infection with implant exposure after thoracotomy who met the inclusion criteria were admitted to Peking University First Hospital, including 9 males and 7 females, aged from 21 to 74 years. The infected wounds were subjected to multiple thorough debridement and negative-pressure wound therapy until the infection was controlled, and contrast-enhanced magnetic resonance imaging (MRI) examination was used to guide the operation after every debridement. During the operation, 5 cases of deep mediastinal pacing lead exposure, 1 case of deep mediastinal pacing lead exposure combined with pericardial patch exposure, 5 cases of pericardial patch exposure, 3 cases of artificial blood vessel exposure, and 2 cases of artificial blood vessel exposure combined with pericardial patch exposure were observed. Partial or complete implants were removed during debridement, therefore 8 patients who completely removed the middle mediastinum implants during the operation were included in the implant complete removal group. Then, according to the defects of the sternum and its surrounding soft tissue, unilateral or bilateral pectoralis major muscle flaps were used for chest wall reconstruction. The remaining 8 patients whose implants could not be completely removed were included in the implant partial removal group. The greater omentum flaps were used to cover the implants and fill the mediastinal defects. Two weeks later, the thigh medium-thickness skin grafts were transplanted on the surface of the greater omentum flaps. After debridement, the wound area was 20 cm×6 cm to 35 cm×10 cm. The area of pectoralis major muscle flap ranged from 15 cm×8 cm to 20 cm×10 cm, and the area of greater omentum flap ranged from 30 cm×15 cm to 40 cm×25 cm. The bacterial culture and high throughput sequencing test results of wound tissue samples of all patients were counted in the first debridement surgery. The hospitalization time, the time for C reactive protein (CRP) to decrease to normal level, and the number of operations were counted for all patients, and the above indexes of the two groups of patients were compared. During the follow-up, the wound recurrence of the patients was observed.  Results  The positive ratio of bacterial culture in wound tissue samples was 14/16 in the first debridement surgery, and the positive ratio of high throughput sequencing test was 16/16, with staphylococcus aureus as the bacteria causing most infection among patients. Except for one patient who died during the treatment (a patient in implant partial removal group), the hospitalization time was (56±5) d, the time for CRP to decrease to normal level was (18.9±2.2) d, and the number of operations was (4.5±0.5) times in the remaining patients. Compared with those in implant partial removal group, the length of hospital stay and the time for CRP to decline to normal level of patients in implant complete removal group were significantly shorter (with t values of 3.12 and 3.12, respectively, P<0.05), and the number of operations of patients in implant complete removal group was significantly decreased (t=3.38, P<0.05). All 15 surviving patients were followed up for more than 6 months, and no recurrence of mediastinitis was observed.  Conclusions  The treatment of complex mediastinal infection with exposed implants after thoracotomy is difficult, especially the wounds when the implants cannot be completely removed during debridement. The application of contrast-enhanced MRI examination combined with transplantation of tissue flap such as greater omentum flap and pectoralis major muscle flap can achieve good repair effect.
Original Article
Relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns
Zuo Fangqing, Su Jiaqing, Li Yang, Zhang Lijuan, Lan Yingying, Chen Yu, Gong Yali, Chen Yajie, Li Junda, Peng Yizhi, Luo Gaoxing, Yuan Zhiqiang
2024, 40(6): 543-550. doi: 10.3760/cma.j.cn501225-20240228-00075
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  Objective  To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.  Methods  The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group (n=54) and the survival group (n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately.  Results  Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups (P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups (P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L (P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05).  Conclusions  There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.
Clinical effect of unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap in repairing huge pressure ulcers in the sacrococcygeal region
Li Jun, Liu Mengdong, Zhu Liang, Luo Yuming, Yang Qiying, Gao Xiaowen, Han Juntao
2024, 40(6): 551-556. doi: 10.3760/cma.j.cn501225-20231031-00158
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  Objective  To explore the feasibility and clinical effects of unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap in repairing huge pressure ulcers in the sacrococcygeal region.  Methods  The study was a retrospective observational study. From June 2020 to April 2023, 15 patients with stage Ⅳ pressure ulcers with sacrococcygeal defect area greater than 10.0 cm×10.0 cm who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 8 males and 7 females, aged from 30 to 86 years. The pressure ulcers before debridement were all accompanied by different degree of infection and necrosis. Debridement and negative pressure sealing and irrigation treatment were performed in stage Ⅰ. After debridement, the skin and soft tissue defect area was 12.0 cm×10.5 cm to 20.0 cm×17.0 cm. After the wound bed infection was controlled, unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap was used to repair the pressure ulcer wounds in stage Ⅱ. The perforator flap area was 12.0 cm×7.0 cm to 16.0 cm×10.5 cm. The donor area wound was sutured directly. After operation, the survival, complications, and wound healing of flap donor area were observed. During regular follow-up, the recurrence of pressure ulcers, the appearance and texture of the flap, and the scars in the donor site were observed.  Results  After operation, 1 patient had fluid accumulation under the flap and survived after drainage and dressing change. The flaps of the other patients survived well without infection, local necrosis, and sinus formation under the flap. The wounds in the donor area healed well. All patients were followed up for more than 6 months, and there was no recurrence of pressure ulcers. The appearance of the flap was not bloated, the texture was soft, and the compression resistance and elasticity were good. The donor site wound healed well without obvious scar.  Conclusions  The surgical method of repairing giant sacrococcygeal pressure ulcers with unilateral superior gluteal artery perforator propeller flap combined with contralateral centripetal advancement flap is simple and easy to operate. It can repair large defect area with the donor area being sutured directly, which is worthy of clinical promotion.
Application effects of indwelling nasoenteric tubes under bedside electromagnetic navigation in patients with extremely severe burns
Zhang Lingling, Zhang Wei, Wang Congcong, Zhang Liping
2024, 40(6): 557-563. doi: 10.3760/cma.j.cn501225-20231010-00108
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  Objective  To investigate the application effects of indwelling nasoenteric tubes under bedside electromagnetic navigation in patients with extremely severe burns.  Methods  This study was a retrospective cohort study. The 27 patients with extremely severe burns who were admitted to Shandong Provincial Hospital Affiliated to Shandong First Medical University (hereinafter referred to as the hospital) from April 2017 to December 2021 and inserted nasoenteric tubes by blind insertion within 24 h of admission were included in blind insertion group, including 17 males and 10 females, aged (52±16) years. The 33 patients with extremely severe burns who were admitted to the hospital from January 2022 to October 2023 with indwelling nasoenteric tubes under bedside electromagnetic navigation within 24 h of admission were included in electromagnetic navigation group, including 24 males and 9 females, aged (50±15) years. The one-time success rate of indwelling nasoenteric tube and the time of indwelling nasoenteric tube were recorded. Within 0.5 h after indwelling nasoenteric tube, the satisfaction of patients with indwelling nasoenteric tube was assessed using 5-grade Likert scale, and the satisfaction rate was calculated. Numerical rating scale was used to assess the degree of low back pain in the operators of indwelling nasoenteric tube (hereinafter referred to as operators) before and immediately after indwelling nasoenteric tubes, and the incidence rate of low back pain in operators immediately after indwelling nasoenteric tubes was calculated.  Results  The one-time success rate of indwelling nasoenteric tube of patients in electromagnetic navigation group was 96.97% (32/33), which was significantly higher than 74.07% (20/27) in blind insertion group (P<0.05). The time of indwelling nasoenteric tube of patients in electromagnetic navigation group was 10 (8, 13) min, which was significantly shorter than 30 (22, 40) min in blind insertion group (Z=-6.17, P<0.05). Within 0.5 h after indwelling nasoenteric tube, the satisfaction rate of patients with indwelling nasoenteric tube in electromagnetic navigation group was 96.97% (32/33), which was significantly higher than 70.37% (19/27) in blind insertion group (P<0.05). Before indwelling the nasoenteric tubes, the low back pain scores of operators of patients in the 2 groups were both 0. Immediately after indwelling nasoenteric tubes, the incidence rate of low back pain in operators of patients in electromagnetic navigation group was 45.45% (15/33), which was significantly lower than 85.19% (23/27) in blind insertion group (P<0.05).  Conclusions  Indwelling nasoenteric tube under bedside electromagnetic navigation has high success rate, short time, and high satisfaction with indwelling nasoenteric tube in patients. Meanwhile, it can greatly reduce the incidence of the operators' occupational low back pain, and it is beneficial to start enteral nutrition as early as possible for patients with extremely severe burns.
Clinical effects of anterolateral femoral or anteromedial femoral perforator flaps in repairing skin and soft tissue defects after resection of cutaneous squamous cell carcinoma
Liu Ruobing, Zheng Deyi, Wang Baoyun, Li Weiren
2024, 40(6): 564-571. doi: 10.3760/cma.j.cn501225-20231114-00193
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  Objective  To explore the clinical effects of anterolateral femoral or anteromedial femoral perforator flaps in repairing skin and soft tissue defects after resection of cutaneous squamous cell carcinoma (CSCC).  Methods  This study was a retrospective observational study. From July 2015 to July 2022, 21 patients with CSCC were treated in the Department of Burns and Plastic Surgery of Guizhou Provincial People's Hospital, including 15 males and 6 females, aged from 27 to 74 years. The area of skin and soft tissue defects after extended resection of CSCC was 7.5 cm×4.0 cm to 23.0 cm×8.5 cm. The wounds in 18 patients were repaired with anterolateral femoral perforator flaps; variations of perforating branch of the descending branch of lateral circumflex femoral artery were observed in 3 patients during the operation, and the wounds were repaired with anteromedial femoral perforator flaps. The flap areas were 8.0 cm×5.0 cm to 25.0 cm×10.0 cm. The wounds in the donor areas were sutured directly in 19 patients, and the wounds in the donor areas were repaired with thin and medium-thickness skin grafts in the contralateral thigh in 2 patients. The postoperative survival of flaps and the occurrence of vascular crisis were observed. The length of operation and the hospitalization day were recorded. The recurrence of tumor, the appearances of the donor and recipient areas of flaps, the function of the flap donor area were followed up. At the last follow-up, the satisfaction degree of patients for the curative effects was evaluated.  Results  The flaps survived in 20 patients, while the vascular crisis occurred in 1 patient within 48 hours after operation, and the flap survived after immediate emergency operation. The length of operation was 4 to 5 hours, and the hospitalization day was 15 to 38 days. The patients were followed up for 1 to 6 years after operation, there was no local tumor recurrence, the color and texture of the flaps were with no obvious differences to those of the surrounding tissue, and the elasticity and appearance were good. The skin grafts in the flap donor areas of 2 patients survived well with local pigmentation. There was only linear scar in the flap donor areas of all patients, and there were no significant effects on sensory and motor functions. At the last follow-up, fifteen patients were satisfied with the curative effect, and 6 patients were generally satisfied with the curative effect.  Conclusions  For skin and soft tissue defects after CSCC resection, the anterolateral femoral perforator flaps can be used preferentially. In the case of variation of the perforating branch of descending branch of the lateral circumflex femoral artery, the anteromedial femoral perforator flap is selected. The areas of the two flaps are large and can be adjusted according to the amount of defect tissue, thus accurately and effectively repairing skin and soft tissue defects after CSCC resection. The postoperative appearance and function are good.
Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method
Wu Honglin, Chen Yongfei, Li Shuting, Yang Hao, Li Xiaohui, Tang Bing, Zhu Jiayuan, Hu Zhicheng
2024, 40(6): 572-578. doi: 10.3760/cma.j.cn501225-20240203-00046
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  Objective  To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.  Methods  This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells.  Results  The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS (PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS (P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS (P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS (P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells (P>0.05).  Conclusions  From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.
Effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats
Wang Baohong, Zhang Yanbing, Zhang Xianping, Li Yuting, Wu Zhihui, Hu Rongying, Zhao Shiyue, Jiang Hongna, Yao Yuwei, Dong Jianda
2024, 40(6): 579-588. doi: 10.3760/cma.j.cn501225-20231219-00253
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  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.
Review
Research advances on the roles of metabolic remodeling and protein acylation modification in keloids
Mu Zelan, Teng Yongxiang, Zhang Jian, Bai Nan, Fu Yanjie
2024, 40(6): 589-593. doi: 10.3760/cma.j.cn501225-20231207-00229
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Abstract:
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.
Research advances on the non-coding RNAs carried by exosomes as competitive endogenous RNAs involved in wound healing
Yang Lingjing, Lyu Yehui, Lin Jian
2024, 40(6): 594-599. doi: 10.3760/cma.j.cn501225-20230811-00044
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Abstract:
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.
2024, 40(6): 600-600. doi: 10.3760/cma.j.cn501225-20240515-00177
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Abstract:

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