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2025, Volume 41,  Issue 2

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2025, 41(2): 101-101. doi: 10.3760/cma.j.cn501225-20250119-00029
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2025, 41(2): 102-102. doi: 10.3760/cma.j.cn501225-20250123-00034
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2025, 41(2): 103-105. doi: 10.3760/cma.j.cn501225-20250107-00012
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2025, 41(2): 106-108. doi: 10.3760/cma.j.cn501225-20250123-00033
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Expert Forum
New progresses in thumb and finger reconstruction
Wang Zengtao, Liu Huanlong, Hao Liwen, Qiu Shenqiang, Liu Linfeng, Chen Chao
2025, 41(2): 109-119. doi: 10.3760/cma.j.cn501225-20240814-00305
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For centuries, people have been searching for ways to reconstruct the mutilated thumb and fingers. Among the hundreds of operation methods that have appeared, the method of toe transplantation to reconstruct the thumb and fingers, which appeared in the second half of the 19th century, had the best effect. However, due to the limitation of technical level at that time, only the pedicled toe could be transplanted to reconstruct the thumb and fingers. During the treatment period, the patient was in an inappropriate position where the hand and foot were fixed together for a long time, and the nerve was not repaired, so the thumb and fingers reconstructed after surgery had poor feeling. Therefore, it has not been widely used. It was not until 1966 when Yang Dongyue succussed in reconstructing the thumb using a free toe transplant with blood vessel anastomosis that toe transplantation gradually became the mainstream method of thumb and finger reconstruction. The appearance and function of the thumb and finger reconstructed by toe transplantation are still very different from that of the normal thumb and finger. Moreover, when multiple thumbs and fingers are defective, the transplantation of multiple toes for repair will cause great damages to the foot, so it is not suitable to reconstruct more than three thumb and fingers using toes in the same period. In 2007, Wang Zengtao proposed the concept of "full-finger reconstruction of thumb and fingers" and a series of new operation methods: new fingers were designed and assembled by means of using a variety of tissue combination assembly, which changed the traditional method of toe transplantation to reconstruct thumb and fingers, and the method of replacing thumb and fingers by toes was changed to manufacturing new thumb and fingers so that the toes could be retained and the thumb and fingers could be reconstructed with approximately normal shape and function. In recent years, the concept and series of new operation methods of thumb and finger reconstruction have been popularized at home and abroad. This paper focuses on the development of full-finger reconstruction of thumb and fingers.
Mechanisms and intervention strategies of angiogenesis disorders in diabetic foot ulcers
Tao Ke, Cao Tao, Hao Tong
2025, 41(2): 120-126. doi: 10.3760/cma.j.cn501225-20241204-00474
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Nerve and vascular damage are important factors affecting the occurrence and development of diabetic foot ulcer (DFU). Lower extremity vascular injury combined with microangiogenesis disorder caused by various factors including hyperglycemia, neurotrophic impairment, ischemia, hypoxia, and infection is an important reason for delayed healing of DFU wound. Angiogenesis is a pathophysiological process in which endothelial cells, endothelial progenitor cells, and stem cells rebuild microvascular network under the regulation of various cytokines and microenvironment, which is a key step in the process of DFU wound healing. The mechanisms of DFU wound angiogenesis disorders are complex and diverse. This article summarizes the new progress of DFU microvascular injury mechanism and intervention strategies from three aspects including angiogenesis microenvironment, neuronutrition, and cell function to provide new ideas for the treatment of DFU.
Original Article·Diabetic Wounds
Effect and mechanism of Andrias davidianus skin mucopolysaccharides on full-thickness skin defect wound healing in diabetic mice
Gou Weiming, Yang Peng, Lu Yifei, Zhang Xiaorong, Qin Yiming, Li Jingyuan, Huang Yong, Zhang Qing, Luo Gaoxing
2025, 41(2): 127-136. doi: 10.3760/cma.j.cn501225-20240725-00280
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  Objective  To explore the effect and mechanism of Andrias davidianus skin mucopolysaccharides (ASMP) on full-thickness skin defect wound healing in diabetic mice.  Methods  This study was an experimental study. The ASMP with polysaccharide content of (70.0±0.3)% was prepared; the proliferation activity of human umbilical vein endothelial cells (HUVECs) was detected by cell counting kit-8, showing that the optimal concentration of ASMP was 0.05 mg/mL. The HUVECs were taken and divided into blank control group, vascular endothelial growth factor (VEGF) group, and ASMP group according to the random number table method (the same grouping method below), which were cultured with conventional medium and the media containing 50 ng/mL VEGF and 0.05 mg/mL ASMP, respectively, and then cultured under hypoxic (with volume fraction of oxygen being 5%) and normal-oxygen conditions for 12 hours, and the length of tube formation was observed. Human monocytic leukemia cells were induced with phorbol ester to differentiate into M0 macrophages. These cells were then divided into blank control group, lipopolysaccharide (LPS) group, and ASMP group, which were cultured respectively using conventional medium, LPS-containing medium followed by conventional medium, and LPS-containing medium followed by 0.05 mg/mL ASMP-containing medium. After 48 hours of culture, the expressions of CD86 and CD206 proteins (expressed as relative fluorescence intensity, the same below) were measured by immunofluorescence, and the mRNA expression levels of arginase-1 (Arg1) and CD206 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Eighteen male C57 mice aged 8-10 weeks were used, and diabetic model was successfully established using streptozotocin combined with a high-fat and high-sugar diet. Full-thickness skin defect wounds were created on the backs of the mice, and the mice were divided into blank control group, alginate dressing group, and ASMP group (with 6 mice in each group), which were treated with physiological saline, alginate dressing, and ASMP, respectively. Wound healing was observed on post injury day (PID) 3, 7, 10, and 14, and the wound healing rates of mice were calculated. On PID 7, the expressions of CD31 and CD206 proteins in the wound tissue of mice were observed by immunofluorescence. On PID 14, the thickness of granulation tissue in wounds of mice was observed by hematoxylin-eosin staining. The sample size for all experiments was 3.  Results  After 12 hours of culture in normal-oxygen condition, compared with that in blank control group, the tube formation length of HUVECs in VEGF and ASMP groups was significantly increased (with q values of 10.08 and 16.91, respectively, P<0.05). After 12 hours of culture in hypoxic condition, compared with that in blank control group, the tube formation length of HUVECs in VEGF and ASMP groups was significantly increased (with q values of 11.61 and 16.91, respectively, P<0.05); compared with that in VEGF group, the tube formation length of HUVECs in ASMP group was significantly increased (q=5.30, P<0.05). After 48 hours of culture, the relative fluorescence intensity of CD206 protein in M0 macrophages in ASMP group was 31.90±1.76, significantly higher than 1.00±0.25 in blank control group and 2.21±0.42 in LPS group (with q values of 50.75 and 48.75, respectively, both P values<0.05); the relative fluorescence intensity of CD86 protein was 5.82±0.63, significantly lower than 53.73±4.61 in LPS group (q=30.90, P<0.05). After 48 hours of culture, the mRNA expressions of Arg1 and CD206 in M0 macrophages in ASMP group were significantly higher than those in blank control group (with q values of 35.02 and 13.09, respectively, P<0.05) and LPS group (with q values of 32.24 and 11.24, respectively, P<0.05). On PID 3, there was no statistically significant difference in intercomparison in the wound healing rate of mice among the blank control, alginate dressing, and ASMP groups (P>0.05). Compared with those in blank control group, the wound healing rates of mice in alginate dressing group on PID 10 and 14 were significantly increased (with q values of 11.76 and 12.50, respectively, P<0.05), and the wound healing rates of mice in ASMP group on PID 7, 10, and 14 were significantly increased (with q values of 5.84, 15.90, and 14.96, respectively, P<0.05); compared with those in alginate dressing group, the wound healing rates of mice in ASMP group on PID 7 and 10 were significantly increased (with q values of 4.77 and 4.14, respectively, P<0.05). On PID 7, the relative fluorescence intensity of CD31 protein in wound tissue of mice in alginate dressing and ASMP groups was significantly stronger than that in blank control group (with q values of 7.63 and 16.85, respectively, P<0.05); the relative fluorescence intensity of CD31 protein in wound tissue of mice in ASMP group was significantly stronger than that in alginate dressing group (q=9.22, P<0.05). On PID 7, the relative fluorescence intensity of CD206 protein in wound tissue of mice in alginate dressing and ASMP groups was significantly stronger than that in blank control group (with q values of 8.76 and 29.36, respectively, P<0.05), and the relative fluorescence intensity of CD206 protein in wound tissue of mice in ASMP group was significantly stronger than that in alginate dressing group (q=20.61, P<0.05). On PID 14, the wound granulation tissue of mice in ASMP group was thicker compared with that in blank control group and alginate dressing group.  Conclusions  ASMP can significantly enhance the ability of new blood vessel formation and optimize the immune microenvironment by promoting HUVEC tube formation as well as inducing macrophages to polarize toward the M2 type, thereby accelerating full-thickness skin defect wound healing in diabetic mice.
Targeted energy metabolomics study on wound tissue of diabetic rats
Wang Xiaoyang, Hu Yujie, Wang Xiaochuan, Zhao Jie, Zhang Jixun, Jiang Duyin
2025, 41(2): 137-144. doi: 10.3760/cma.j.cn501225-20241014-00385
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  Objective  To explore the change of energy metabolism in wound tissue of diabetic rats.  Methods  This study was an experimental study. Six 8-week-old male Sprague-Dawley rats were divided into diabetic group inflicted with a diabetic full-thickness skin defect wound and control group only inflicted with a full-thickness skin defect wound according to the random number table method, with 3 rats in each group. The wound healing rates of rats in the two groups were calculated at 14 d after operation. The wound tissue of two groups of rats was collected at 14 d after operation, the targeted energy metabolomics detection was carried out by chromatography-mass spectrometry analysis, and the differential energy metabolites in the wound tissue were screened with significant change in the expression between the two groups of rats. The Kyoto encyclopedia of genes and genomes enrichment analysis was performed on the differential energy metabolites.  Results  At 14 d after operation, the wound healing rate of rats in diabetic group was (68.3±2.8)%, which was significantly lower than (98.1±1.2)% in control group (t=16.92, P<0.05). At 14 d after operation, compared with those in control group, the expressions of cis-aconitic acid, nicotinamide adenine dinucleotide phosphate, and 5'-guanosine diphosphate were significantly increased in wound tissue of rats in diabetic group (with t values of 4.74, 3.09, and 3.99, respectively, P<0.05), the expressions of L-malic acid and lactic acid were significantly decreased (with t values of 3.45 and 12.20, respectively, P<0.05), and there were no statistically significant differences in the expression levels of the other 21 energy metabolites in wound tissue of rats in the two groups (P>0.05). The five differential energy metabolites were enriched mainly in the glucagon, Rap1, Ras, hypoxia-inducible factor 1 signaling pathways as well as the tricarboxylic acid cycle, pyruvate metabolism, mitochondrial autophagy,and endocytosis pathways.  Conclusions  The expressions of lactic acid and L-malic acid in wound tissue of diabetic rats decreased, while the expressions of cis-aconitic acid, nicotinamide adenine dinucleotide phosphate, and 5'-guanosine diphosphate increased. The differential energy metabolites were mainly enriched in oxidative stress, energy regulation, inflammatory reaction, and other related signaling pathways or pathways.
Influence and mechanism of bone marrow mesenchymal stem cells overexpressing growth arrest specific 6 on full-thickness skin defect wounds in diabetic mice
Liu Pei, Wang Chao, Wei Qijian, Li Yuteng, Cui Lijun, Wang Changchuan, Zhang Fan, Ma Ling, Tian Xuan
2025, 41(2): 145-154. doi: 10.3760/cma.j.cn501225-20241024-00409
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  Objective  To investigate the influence and mechanism of bone marrow mesenchymal stem cells (BMSCs) overexpressing growth arrest specific 6, i.e. GAS6/BMSCs on full-thickness skin defect wounds in diabetic mice.  Methods  This study was an experimental study. Twelve 8-week-old male C57BL/6J mice were divided into a control wound group with only full-thickness skin defects and a diabetic wound group with diabetic full-thickness skin defects according to the random number table method, with 6 mice in each group. The wound healing rates were calculated at 3, 7, 14, and 21 days after injury. At 21 days after injury, wound tissue specimens were collected for hematoxylin-eosin staining to observe the histopathological conditions; Masson staining was performed to detect collagen deposition; immunohistochemical staining was performed to detect the number of proliferating cell nuclear antigen (PCNA)-positive cells and CD31-positive cells, representing cell proliferation and capillary density, respectively; immunofluorescence staining was performed to detect the number of F4/80 and myeloperoxidase (MPO) double-positive cells, indicating efferocytosis. Two 4-week-old male C57BL/6J mice were used to extract BMSCs, and GAS6/BMSCs were constructed through adenovirus transfection and successfully identified. Eighteen 8-week-old male C57BL/6J mice were used to create diabetic full-thickness skin defect wound models and divided into phosphate buffered solution (PBS) group, BMSC group, and GAS6/BMSC group (with 6 mice in each group) according to the random number table method. Immediately after injury, PBS, BMSC single-cell suspension, and GAS6/BMSC single-cell suspension were injected locally into the wounds of the three groups of mice, respectively. The wound healing rates were calculated, and the cell proliferation, capillary density, and efferocytosis were detected at the same time points as the previous experiments.  Results  At 3, 7, 14, and 21 days after injury, the wound healing rates of mice in diabetic wound group were significantly lower than those in control wound group (with t values of 7.99, 8.62, 9.80, and 5.85, respectively, P<0.05). Compared with those in control wound group, the wound tissue of mice in diabetic wound group showed the infiltration of a large number of inflammatory cells and reduced collagen deposition at 21 days after injury. At 21 days after injury, the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in diabetic wound group were significantly less than that in control wound group (with t values of 6.61 and 5.38, respectively, P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in diabetic wound group was 3.3±0.8, which was significantly less than 12.7±1.8 in control wound group (t=11.00, P<0.05). At 14 and 21 days after injury, the wound healing rates of mice in BMSC group were significantly higher than those in PBS group (P<0.05); at 3, 7, 14, and 21 days after injury, the wound healing rates of mice in GAS6/BMSC group were significantly higher than those in BMSC group (P<0.05). At 21 days after injury, the number of PCNA-positive cells in the wound tissue of mice in BMSC group was significantly higher than that in PBS group (P<0.05), and the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in GAS6/BMSC group were significantly higher than that in BMSC group (P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in BMSC group was 4.2±1.2, which was similar to 3.5±1.1 in PBS group (P>0.05); the number of F4/80 and MPO double-positive cells in the wound tissue of mice in GAS6/BMSC group was 8.2±1.2, which was significantly more than that in BMSC group (P<0.05).  Conclusions  Dysfunctional efferocytosis of macrophage exists in the full-thickness skin defect wounds of diabetic mice, while GAS6/BMSC can promote wound healing by restoring the efferocytosis of macrophages.
Original Article
Effect of self-made static progressive braces in the stepwise treatment of hand flexion dysfunction caused by scar contracture after burn injury
Zhao Haiyang, Zhou Qin, Liu Jiaqi, Zhang Wanfu, Zhu Chan, Xu Jing, Han Juntao, Hu Dahai, Guan Hao
2025, 41(2): 155-162. doi: 10.3760/cma.j.cn501225-20240606-00216
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  Objective  To explore the effect of self-made static progressive braces in the stepwise treatment of hand flexion dysfunction caused by scar contracture after burn injury.  Methods  This study was a retrospective observational study. From January 2022 to March 2024, the First Affiliated Hospital of Air Force Medical University admitted twenty-nine patients who met the inclusion criteria and used the self-made static progressive braces for stepwise treatment of hand flexion dysfunction caused by scar contracture, including 23 males and 6 females, aged 16 to 55 years. The depth of burn on the back of the hand was deep partial-thickness to full-thickness. The self-made static progressive brace referred to the self-made static progressive joint distractor and the self-made static progressive hand flexion distractor. The stepwise treatment was adopted. In the first stage, in-hospital treatment for 2 to 4 weeks was selected. The treatment contents included conventional rehabilitation training and training on the application of the self-made joint distractors. When the active flexion range of motion of the metacarpophalangeal joint was ≥60°, the second stage of treatment was carried out, that is, two weeks of home remote rehabilitation treatment. The treatment contents included individualized exercise training such as training with self-made static progressive joint distractors and training with self-made static progressive hand flexion distractors. Adverse events such as blister, brace compression, and tissue strain during the stepwise treatment were recorded. After the end of the stepwise treatment, the active flexion of the affected hand was observed. During follow-up, the total active range of motion of the affected hand was measured, and the extensibility of the scar and skin and soft tissue on the back of the affected hand and the patient's satisfaction with the therapeutic effect were evaluated. At the last follow-up, the function of the affected hand was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association.  Results  During the stepwise treatment, a small amount of blisters developed on the skin at the wrist joint in 2 patients, which was cured after symptomatic treatment; the other patients had no adverse events such as brace compression and tissue strain. After the end of the stepwise treatment, the active flexion function of the hand was better, and the fist could be basically clenched. After 1-3 months of follow-up, the total active range of motion of the affected hand was 200-245°; the scar on the back of the hand was soft and light-colored, and the skin and soft tissue was malleable. Twenty-two patients were very satisfied with the curative effect, 6 patients were satisfied, and 1 patient was dissatisfied. At the last follow-up, there were 20 cases with excellent hand function and 9 cases with good hand function.  Conclusions  The stepwise treatment of hand flexion dysfunction caused by scar contracture after burn injury with self-made static progressive braces has a good effect and few complications. Moreover, the two self-made static progressive distractors are convenient in material acquisition, simple to make, cost-effective, and highly practical, which is worthy of clinical promotion.
Research on the feasibility of dynamic contrast-enhanced magnetic resonance imaging in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns
Ruan Peng, Sun Siqin, Ge Yinghong, Zha Yunfei
2025, 41(2): 163-170. doi: 10.3760/cma.j.cn501225-20240517-00183
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  Objective  To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.  Methods  This study was an experimental study. Thirty-two male big ear white rabbits aged 6-8 months were assigned into electric burn group of 20 rabbits with high-voltage electric burns in the right lower limb and control group of 12 rabbits with sham injury in the right lower limb using the random number table method. At 0.5, 24.0, 48.0, and 72.0 h post injury, the lower limbs of rabbits in the two groups underwent axial fast spin echo T1-weighted imaging, fast spin echo T2-weighted imaging, and DCE-MRI examination. A reference region-based hemodynamic model was applied to obtain the blood perfusion parameters of skeletal muscle in the injured limbs, including the volume transfer constant Ktrans value and rate constant Kep value. The skeletal muscle tissue from the electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury and the control group of rabbits at 0.5 h post injury was harvested for immunohistochemical staining to observe the microvascular changes and calculate the microvascular density (MVD). The correlation between the Ktrans and Kep values and the MVD of skeletal muscle tissue in electric burn group of rabbits at 0.5-72.0 h post injury was analyzed. The number of samples was 5 in the electric burn group, and the number of samples was 3 in the control burn group.  Results  From 0.5-72.0 h post injury, the Ktrans and Kep values in skeletal muscle tissue of electric burn group of rabbits exhibited the trends of increase first and decrease then, both of which reached peak values at 24.0 h post injury. The Ktrans values at 0.5, 24.0, 48.0, and 72.0 h post injury (with t values of -15.77, -14.91, -40.35, and -40.25, respectively, P<0.05) and the Kep values at 0.5, 24.0, and 48.0 h post injury (with t values of -5.39, -6.82, and -6.83, respectively, P<0.05) in skeletal muscle tissue in electric burn group of rabbits were significantly higher than those in control group. The MVD in skeletal muscle tissue in control group of rabbits at 0.5 h post injury and in electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury was (24.7±3.5), (21.8±2.2), (40.8±9.1), (16.4±2.4), and (9.8±0.8) per mm², respectively. The MVD in skeletal muscle tissue in electric burn group of rabbits at 24.0 h post injury was significantly higher than that in control group at 0.5 h post injury (t=2.89, P<0.05), and the MVD in skeletal muscle tissue at 48.0 and 72.0 h post injury was significantly lower than that in control group at 0.5 h post injury (with t values of 4.01 and 9.52, respectively, P<0.05). The Ktrans and Kep values of skeletal muscle tissue in rabbits in electric burn group were significantly positively correlated with microvascular density at 0.5 to 72.0 h post injury (with both r values of 0.95, P<0.05).  Conclusions  The quantitative perfusion parameters Ktrans and Kep values of DCE-MRI can effectively reflect the microcirculatory perfusion changes of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.
Establishment and clinical application effects of a three-dimensional navigation process for design and resection of perforator flaps based on multi-detector computed tomography angiography
Yin Qixiang, Mi Jingyi, Cai Huazhong, Zhou Feng, Yao Qun, Hua Yong
2025, 41(2): 171-179. doi: 10.3760/cma.j.cn501225-20240407-00123
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  Objective  To establish a three-dimensional navigation process for design and resection of perforator flaps based on multi-detector computed tomography angiography (MDCTA) and to explore its clinical application effects.  Methods  This study was a retrospective observational study. From January 2021 to October 2023, 7 patients and 6 patients with post-traumatic skin and soft tissue defects in extremity and conformed to the inclusion criteria were admitted to the Affiliated Hospital of Jiangsu University and Wuxi No. 9 People's Hospital, respectively. There were 8 males and 5 females, aged 21 to 68 years. Nine patients had wounds on the hand and 4 patients had wounds on the foot. The wound area after debridement ranged from 8.0 cm×6.0 cm to 18.0 cm×17.0 cm. Through the three-dimensional navigation process based on MDCTA, 14 perforator flaps were designed and resected, including 11 free anterolateral thigh perforator flaps and 3 pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain, with flap size ranging from 9.0 cm×6.0 cm to 20.0 cm×15.0 cm. Six wounds in the flap donor sites were directly sutured, and eight wounds in the flap donor sites were transplanted with skin grafts. The consistency of the location, type, and source of the perforators was compared between the preoperative navigation display and actual intraoperative detection. Immediately after surgery, the coverage of wound by the flap was evaluated according to the self-made criteria. The postoperative flap survival was observed. The occurrence of complications was observed during follow-up. At the last follow-up, the appearance of the flaps was observed, the blood supply of the flaps and the hand function of the 9 patients with hand trauma were evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the foot function of the 4 patients with foot trauma was assessed using the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scoring System.  Results  The location, type, and source of the perforators displayed in preoperative navigation were consistent with the actual intraoperative detection. Immediately after surgery, the coverage of the wounds by 11 flaps was rated as excellent, and that of 3 flaps was rated as moderate. Postoperatively, 13 flaps survived completely, and 1 flap had partial necrosis, which healed after a full-thickness skin grafting from the thigh. Patients were followed up for 4 to 24 months postoperatively, one patient developed a hematoma under the flap, and one patient had local infection. At the last follow-up, the flaps of all patients were good in color and texture, and 5 patients with bloated flaps post operation had good appearance after thinning surgery; the blood supply was excellent in 12 flaps and was good in 2 flaps; among patients with hand trauma, the hand function was rated as excellent in 2 cases, good in 4 cases, and poor in 3 cases; among patients with foot trauma, the foot function was rated as excellent in 3 cases and good in 1 case.  Conclusions  The three-dimensional navigation process for design and resection of perforator flaps based on MDCTA realizes precise evaluation of perforator vessels in flap donor sites and skin and soft tissue defects in the recipient sites. Guided by the three-dimensional navigation process, the application of free anterolateral thigh perforator flaps and pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain in repairing skin and soft tissue defects in extremity realizes precise surgery, reducing flap donor site injury and achieving excellent clinical outcomes.
Mendelian randomization analysis of the causal relationships between human inflammatory proteins and keloids
Li Tao, Zhu Chenchen, Chen Jinyuan, Li Puzhen, Jin Peisheng, Li Xueyang
2025, 41(2): 180-187. doi: 10.3760/cma.j.cn501225-20240526-00198
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  Objective  To explore the causal relationships between human inflammatory proteins and keloids.  Methods  This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.  Results  Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids (P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids (P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids (P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP.  Conclusions  Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.
Review
Research advances on the application of recombinant human collagen biomaterials in the field of tissue engineering
Liu Huan, Aobuliaximu Yakupu, Jin Ronghua, Zhang Wei, Han Chunmao, Wang Xingang
2025, 41(2): 188-194. doi: 10.3760/cma.j.cn501225-20240229-00081
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Extensive tissue and organ defects caused by major trauma and burns are common problems in clinical practice. Recombinant human collagen biomaterials, with advantages including impeccable biocompatibility, customization, stable amino acid sequence, low immunogenicity, and inherent biodegradation, have been widely used in the field of tissue engineering and have broad clinical application prospects. This paper briefly summarizes the design and preparation methods, processing techniques of recombinant human collagen biomaterials and their application in the field of tissue engineering, as well as the latest research advances.
Research advances on the effects of mechanical forces on epithelial cells
Pang Jiayuecheng, Duanmu Ying, Jin Shunxin, Fang Xiaowan, Xiao Shichu, Xia Zhaofan
2025, 41(2): 195-200. doi: 10.3760/cma.j.cn501225-20240611-00222
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Abstract:
There are multiple signaling communication modalities for the biological activities of single cells or groups of cells. The elucidated modalities include neuronal electrical signal communication, long-distance communication mediated by hormones, and short-range signal communication secreted by cells into the extracellular environment, etc. Recently, many studies have shown that mechanical forces are also extensively involved in the information exchange between cells or between cells and the external environment, especially in the signal communication among epithelial cells or between epithelial cells and the extracellular matrix. The cell communication triggered by mechanical forces is instantaneous and rapid, and it affects various activities of both individual epithelial cells and epithelial cell clusters. The mediators of cell communication induced by mechanical forces include actin, myosin, cytoskeleton, and adherens junctions, etc. These mediators trigger processes such as ion flow, activation of signaling pathways, and regulation of transcription factors through mechanical signals, thereby interfering with cell behaviors. This article elaborates on the impacts of mechanical forces on epithelial cells from multiple aspects, including biological signals, three-dimensional folding, collective migration, cell metabolism, carcinogenesis, and epithelial-mesenchymal transition.

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