Objective:To explore the causal relationship between human immune cell phenotypes and keloids.Methods:This study was based on a two-sample Mendelian randomization (MR) analysis. Human immune cell phenotypes were considered as the exposure factors, and keloid was the outcome. Data on immune cell phenotypes (3 757 samples) and keloids (668 samples) were obtained from the genome-wide association study database. Using single nucleotide polymorphisms (SNPs) significantly associated with immune cell phenotypes as instrumental variables with the influence of weak instrumental variables being excluded, two-sample MR analysis was employed to evaluate the causal relationship between 731 human immune cell phenotypes and keloids. The inverse variance weighted (IVW) method was used to infer causal relationships, and the MR-Egger, weighted median, and weighted mode methods were used for validation. For SNPs of immune cell phenotypes meeting the hypothesis, the Cochran Q test was used to assess heterogeneity, and the MR-Egger regression and MR-PRESSO outlier tests were used to evaluate horizontal pleiotropy.Results:A total of 18 204 SNPs meeting the significant threshold ( P<1×10??) were selected as instrumental variables for 731 immune cell phenotypes, and none of these SNPs were weak instrumental variables (with F values all >10). According to the IVW method, 21 immune cell phenotypes were identified with potential causal relationships to keloids, among which the CD62L - monocyte absolute count, CD19 on naive-mature B cell, CD19 on IgD + B cell, CD27 on plasma blast-plasma cell, CD86 on CD62L + myeloid dendritic cell, CD45 on natural killer T cell, CD25 on CD39 + CD4 + regulatory T cell, CD45 on monocytic myeloid-derived suppressor cells, CD8 on effector memory CD8 + T cell, and CD45RA on resting CD4 + regulatory T cell showed significant positive correlations with keloids (with odds ratios of 1.12, 1.09, 1.08, 1.21, 1.13, 1.12, 1.17, 1.11, 1.10, and 1.07, respectively, 95% confidence intervals of 1.03-1.23, 1.02-1.16, 1.01-1.15, 1.06-1.38, 1.02-1.25, 1.01-1.24, 1.03-1.33, 1.00-1.23, 1.00-1.20, and 1.01-1.13, respectively, P<0.05), while the activated and secreted CD4 + regulatory T cell absolute count, CD25 on unswitched memory B cell, plasmacytoid dendritic cell absolute count, CD14 on monocytic myeloid-derived suppressor cells, CD8 on natural killer T cell, CD20 on IgD + CD38 + B cell, CD11c + CD62L - monocyte absolute count, CD66b ++ myeloid cell absolute count, CD11c on granulocytes, CD14 on CD14 + CD16 + monocyte, and CD3 on central memory CD8 + T cell showed significant negative correlations with keloids (with odds ratios of 0.95, 0.93, 0.93, 0.93, 0.91, 0.89, 0.89, 0.88, 0.87, 0.86, and 0.85, respectively, 95% confidence intervals of 0.90-1.00, 0.87-0.99, 0.88-0.99, 0.87-0.99, 0.84-1.00, 0.81-0.98, 0.81-0.98, 0.79-0.99, 0.78-0.96, 0.75-0.99, and 0.74-0.96, respectively, P<0.05). MR-Egger method confirmed the potential causal relationship existing respectively between CD25 on CD39 + CD4 + regulatory T cell, CD86 on CD62L + myeloid dendritic cell, CD19 on IgD + B cell, CD45RA on resting CD4 + regulatory T cell, CD3 on central memory CD8 + T cell and keloids (with odds ratios of 1.32, 1.22, 1.11, 1.09, and 0.73, respectively, 95% confidence intervals of 1.03-1.70, 1.04-1.44, 1.02-1.21, 1.01-1.19, and 0.55-0.95, respectively, P<0.05). The weighted median method confirmed the potential causal relationship existing respectively between CD45 on natural killer T cell, activated and secreted CD4 + regulatory T cells absolute count, CD20 on IgD + CD38 + B cell, CD66b ++ myeloid cell absolute count and keloids (with odds ratios of 1.15, 0.93, 0.87, and 0.83, respectively, 95% confidence intervals of 1.01-1.31, 0.86-1.00, 0.77-0.98, and 0.71-0.96, respectively, P<0.05). Among them, the potential causal relationship between CD20 on IgD + CD38 + B cell and keloids was further verified by the weighted mode method (with odds ratio of 0.86, 95% confidence interval of 0.77-0.97, P<0.05). According to the aforementioned IVW method analysis results, the SNPs associated with the 21 immune cell phenotypes that had a significant causal relationship with keloids showed no significant heterogeneity ( P>0.05) or significant horizontal pleiotropy ( P>0.05). Conclusions:From a genetic perspective, the potential causal relationships between 21 human immune cell phenotypes and keloids have been revealed, of which 10 immune cell phenotypes may be risk factors for keloids, while 11 immune cell phenotypes may act as protective factors for keloids.

Over the course of more than 60 years of development, microsurgical techniques have entered the era of intelligence and digitization. This article focuses on the development of microsurgical techniques in the field of tissue repair in China, provides a detailed analysis of the application of microsurgical techniques in the repair of destructive burn wounds and the reconstruction of post-burn scar contracture deformity, and systematically introduces the flap repair strategies in various tissue forms. With advances of science and technology, and breakthroughs in emerging fields such as tissue engineering, regenerative medicine and gene editing, microsurgical techniques have demonstrated tremendous potential in the area of tissue repair, with broad prospects for future applications.

Objective:To investigate the influence and mechanism of extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADMSCs), i.e. hADMSC-EVs on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by high glucose, with the aim of providing evidence for improving vascular function in diabetic wounds.Methods:This study was an experimental research. The umbilical cords from 5 women aged 25 to 40 years were collected who had normal vaginal delivery at the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Nanchang University from June to September in 2023, and HUVECs were isolated and successfully identified. Adipose tissue was obtained from 6 healthy women aged 25 to 35 years who underwent abdomen liposuction at the Department of Plastic Surgery of the above-mentioned hospital in the same period. After hADMSCs were isolated, hADMSC-EVs were extracted and successfully identified. The fourth passage of HUVECs were cultured in endothelial cell medium containing glucose in a molarity of 33 mmol/L and divided into phosphate buffered solution (PBS) group cultured with PBS, EV group cultured with hADMSC-EVs, and EV+LY294002 group cultured with hADMSC-EVs and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway inhibitor LY294002. Western blotting was used to detect the expressions of PI3K/Akt signaling pathway-related proteins PI3K and Akt, and pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D, interleukin-1β (IL-1β), and IL-18 of cells after 48 hours of culture. A cell counting kit-8 was used to test the proliferation levels of cells at 0 (immediately), 12, 24, 36, 48, 60, and 72 hours of culture. After 48 hours of culture, the cell scratch test was performed and the cell migration rates at 12 and 24 hours after scratching were calculated; the cell Transwell assay was conducted and the number of cells migrating in 24 hours was calculated; the cell tube formation experiment was performed, and the total length of tube formation and the number of branch nodes were measured and counted. The sample size was 3.Results:After 48 hours of culture, the protein expressions of PI3K and Akt of cells in EV group were significantly higher than those in PBS group ( P<0.05), and the protein expressions of PI3K and Akt of cells in EV+LY294002 group were significantly lower than those in EV group ( P<0.05). After 48 hours of culture, the protein expressions of NLRP3, caspase-1, gasdermin D, IL-1β, and IL-18 of cells in EV group were 0.54±0.08, 0.96±0.11, 0.525±0.061, 1.216±0.039, and 1.317±0.023, respectively, which were significantly lower than 2.32±0.11, 1.86±0.07, 1.256±0.113, 2.589±0.084, and 2.042±0.132 in PBS group ( P<0.05); the protein expressions of NLRP3, caspase-1, gasdermin D, IL-1β, and IL-18 of cells in EV+LY294002 group were 1.16±0.05, 1.37±0.06, 0.962±0.028, 1.834±0.017, and 1.803±0.065, respectively, which were significantly higher than those in EV group ( P<0.05). At 12, 24, 36, 48, 60, and 72 hours of culture, the proliferation levels of cells in EV group were significantly higher than those in PBS group ( P<0.05), and the proliferation levels of cells in EV+LY294002 group were significantly lower than those in EV group ( P<0.05). After 48 hours of culture, the cell migration rates at 12 and 24 hours after scratching in EV group were significantly higher than those in PBS group ( P<0.05), and the cell migration rates at 12 and 24 hours after scratching in EV+LY294002 group were significantly lower than those in EV group ( P<0.05); the number of cells migrating in 24 hours in EV group was significantly greater than that in PBS group ( P<0.05), and the number of cells migrating in 24 hours in EV+LY294002 group was significantly less than that in EV group ( P<0.05). After 48 hours of culture, compared with those in PBS group, the total length of tube formation of cells in EV group was significantly prolonged ( P<0.05), and the number of branch nodes was significantly increased ( P<0.05); compared with those in EV group, the total length of tube formation in EV+LY294002 group was significantly shortened ( P<0.05), and the number of branch nodes was significantly decreased ( P<0.05). Conclusions:hADMSC-EVs can inhibit the expression of pyroptosis-related proteins in HUVECs induced by high glucose through the PI3K/Akt signaling pathway and improve the proliferation, migration, and angiogenesis capabilities of HUVECs.

I learned from some specialists in fields of trauma, burns, and tissue repair in different conferences that the new research fields in trauma, burns, and tissue repair combined with biomaterials have been established in recent years. I feel that the direction of scientific research in the subject field characterized by the treatment of "injury" is undergoing new changes, expanding into new fields related to "injury" treatment such as biomaterials and biomedical engineering, especially the close integration with biomaterials. These reflect the characteristics of cross-industry, cross-field, and multi-disciplinary intersection and integration. These new developments could lead to revolutionary breakthroughs in future research and clinical treatment of trauma, burns, and tissue repair. In this paper, I would like to summarize the fruitful achievements in these fields and put forward some suggestions for the next development of the discipline.

Objective:To explore the effects of nutritional therapy based on indirect calorimetry in patients with extremely severe burns during hypermetabolic stage.Methods:This study was a retrospective cohort study. From March 25, 2022 to March 30, 2024, 20 extremely severe burn patients who met the inclusion criteria were admitted to the Department of Burn and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 15 males and 5 females, aged (46±12) years. The patients were divided into death group (6 cases) and survival group (14 cases) according to their treatment outcomes. At the 3 rd, 7 th, 14 th, and 21 st d after injury, the resting energy expenditure (REE) of patients in the two groups was measured by indirect calorimetry once a day, and the nutritional treatment scheme was formulated according to the results of REE. The REE value, levels of albumin and interleukin-6 (IL-6), actual energy intake, and enteral nutrition energy intake of patients in the two groups at the 3 rd, 7 th, 14 th, and 21 st d after injury were collected (the last two indicators were respectively expressed as the mean values of the 3 rd to 6 th, 7 th to 10 th, 14 th to 17 th, and 21 st to 24 th d after injury). The actual energy intake/REE value and enteral nutrition energy intake/actual energy intake were calculated. Results:The REE values of patients in survival group and death group were (8 143±2 328), (9 843±2 610), (10 149±2 248), (9 608±2 838) kJ and (6 816±2 057), (10 691±2 515), (11 031±2 850), (8 990±2 018) kJ, respectively at the 3 rd , 7 th, 14 th, and 21 st d after injury. The REE value and enteral nutrition energy intake of patients in the two groups showed trends of increase first and decrease then from the 3 rd to 21 st d after injury, while the differences in the above two indicators at each time point between the two groups of patients were not statistically significant ( P>0.05). The actual energy intake of patients in survival group at the 21 st d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05), and the enteral nutrition energy intake of patients in death group at the 14 th d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05). There were no statistically significant differences in overall comparison in actual energy intake/REE value and enteral nutrition energy intake/actual energy intake at each time point after injury between and within the two groups of patients ( P>0.05). The level of IL-6 of patients in survival group at the 21 st d after injury was significantly lower than that at the 3 rd and 7 th d after injury, respectively (with both P values <0.05), and significantly higher than that at the 14 th d after injury ( P<0.05); the level of IL-6 of patients in death group at the 21 st d after injury was significantly higher than that at the 3 rd, 7 th, and 14 th d after injury (with P values all <0.05). The albumin level of patients in survival group at the 7 th d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05). Conclusions:The REE value and enteral nutrition energy intake of extremely severe burn patients showed trends of increase first and decrease then, while they have no significant effects on the clinical outcome of the patients. The nutritional treatment scheme based on the indirect calorimetry can basically meet the energy demand of patients with extremely severe burns during hypermetabolic stage. The impacts of the albumin and IL-6 levels on the clinical outcome of extremely severe burn patients still need further research.

Objective:To explore the clinical efficacy of the first dorsal metatarsal artery pedicled lateral toe bilobed flap in repairing the finger pulp defects of two adjacent fingers.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 9 patients with finger pulp defects in two adjacent fingers who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 6 males and 3 females, aged 26 to 48 years. The injured fingers were the index finger and middle finger (5 cases) or the middle finger and ring finger (4 cases). After debridement, the wound area of a single finger ranged from 1.2 cm×0.8 cm to 3.2 cm×2.8 cm. The finger pulp defects of two adjacent fingers were repaired with the first dorsal metatarsal artery pedicled lateral toe bilobed flap, and the two adjacent fingers were sutured together. The area of single flap ranged from 1.5 cm×1.0 cm to 3.5 cm×3.0 cm. The wound in the flap donor site was sutured directly or repaired with full-thickness skin graft from the groin region. The finger separation surgery was performed 3 weeks after surgery. The survival and blood supply of flaps, and survival of skin grafts and wound healing of the donor sites were observed after surgery. During follow-up, the texture, sliding, and shape of the flap, movement function of the finger, and the shape and function of the foot donor site were observed. At the last follow-up, the sensory of the flap was evaluated according to the sensory evaluation standard of the British Medical Research Council, and the hand function was evaluated according to the functional evaluation trial standard for severed finger replantation of the Hand Surgery Society of the Chinese Medical Association. Results:After surgery, all the flaps of 9 patients survived without vascular crisis. The flaps were soft in texture and good in shape. One patient had partial necrosis at the edge of the skin graft in the toe, and the wound healed after dressing change; the skin grafts in the toe in the other 8 patients survived, and the wounds healed well. During follow-up of 12 to 18 months after surgery, the flaps had soft texture, good elasticity, low sliding, and good shape. The finger movement function was normal. The wound in foot donor site recovered well without ulceration and deformity, and walking was not affected. At the last follow-up, the sensation of the flaps was sensitive, of which 8 flaps reached S3 and 10 flaps reached S3 + in sensation, and the two-point discrimination distance of the flaps was 9-13 mm. The functional scores of the affected fingers were 85 to 95, all of which were excellent. Conclusions:The first dorsal metatarsal artery pedicled lateral toe bilobed flap can repair finger pulp defects of two adjacent fingers at the same time, and the appearance, sensation, and function of the affected fingers recovered well after surgery, with less damage to the foot donor site. It is one of good methods to repair finger pulp defects of two adjacent fingers in clinic.

Objective:To investigate the clinical effects of the anterolateral thigh perforator flaps transplantation in repairing the wounds after radical resection of skin malignant tumors in the head, face, and neck.Methods:This study was a retrospective observational study. From May 2020 to December 2023, 27 patients with skin malignant tumors in the head, face, and neck were admitted to the Department of Burns and Plastic Surgery of the First People's Hospital of Kashi Prefecture, including 19 males and 8 females, aged 53 to 89 years. There were 21 cases with squamous cell carcinoma and 6 cases with basal cell carcinoma. The wound area after radical resection of tumors was 9.0 cm×7.0 cm to 27.0 cm×21.5 cm. The wounds were repaired with the lobulated, combined, or various forms of combination of the anterolateral thigh perforator flaps, and the harvesting flap area in single donor site was 10.0 cm×8.0 cm to 27.0 cm×11.0 cm. The wounds in the flap donor sites were closed by suturing in 26 patients, while the wound in the flap donor site in 1 patient was repaired with medium-thickness skin graft in the lower leg. The survival of the flap, and the occurrence of vascular crisis and infection were observed after surgery. During follow-up after surgery, the tumor recurrence, shape and texture of the flaps, and the function and scar formation of the limbs where the donor site was located were observed.Results:Only one patient developed venous crisis of the flap 27 hours after surgery, and the flap survived after vascular exploration and reanastomosis of the vein; the flaps in the other patients survived after surgery. One patient had an infected effusion under the flap after surgery, which healed after dressing change. After 6-36 months of postoperative follow-up, no tumor recurrence was observed; the flap had good appearance, texture, and elasticity; the limb where the donor site was located functioned normally, with only linear scars left.Conclusions:For complex wounds after radical resection of skin malignant tumors in the head, face, and neck, different forms of anterolateral thigh perforator flaps can be used to repair the wounds according to the condition of the wounds, and the wounds in the recipient sites heal well after surgery, with minimal damage to the donor site.

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 19 th 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.

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.

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.