Background: Hypertrophic scarring is the most serious and unmet challenge following burn and trauma injury and often leads to pain, itching and even loss of function. However, the demand for ideal scar prevention and treatment is difficult to satisfy. We aimed to discover the effects and mechanisms of adipose-derived stem cell (ADSC) exosomes in hypertrophic scarring.
Methods: ADSC exosomes were isolated from the culture supernatant of ADSCs and identified by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The effect of ADSC exosomes on wound healing and scar formation was detected by the wound model of BALB/c mice. We isolated myofibroblasts from hypertrophic scar tissue and detected the cell viability, proliferation and migration of myofibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on fibrosis in myofibroblasts, we detected the expression of Smad2 in hypertrophic scar tissue and normal skin and the regulatory mechanism of ADSC exosomes on Smad2. Injection of bleomycin was performed in male BALB/c mice to establish an in vivo fibrosis model while ADSC exosomes were administered to observe their protective effect. The tissue injury of mice was observed via hematoxylin and eosin and Masson staining and related testing.
Results: In this study, we found that ADSC exosomes could not only speed up wound healing and improve healing quality but also prevent scar formation. ADSC exosomes inhibited expression of fibrosis-related molecules such as α-smooth muscle actin, collagen I (COL1) and COL3 and inhibited the transdifferentiation of myofibroblasts. In addition, we verified that Smad2 is highly expressed in both hypertrophic scar tissue and hypertrophic fibroblasts, while ADSC exosomes downregulated the expression of Smad2 in hypertrophic fibroblasts. Further regulatory mechanism analysis revealed that microRNA-125b-5p (miR-125b-5p) is highly expressed in ADSC exosomes and binds to the 3' untranslated region of Smad2, thus inhibiting its expression. In vivo experiments also revealed that ADSC exosomes could alleviate bleomycin-induced skin fibrosis and downregulate the expression of Smad2.
Conclusions: We found that ADSC exosomes could alleviate hypertrophic scars via the suppression of Smad2 by the specific delivery of miR-125b-5p.
{"title":"miR-125b-5p delivered by adipose-derived stem cell exosomes alleviates hypertrophic scarring by suppressing Smad2.","authors":"Chaolei Xu, Hao Zhang, Chen Yang, Ying Wang, Kejia Wang, Rui Wang, Wei Zhang, Chao Li, Chenyang Tian, Chao Han, Mengyang Li, Xu Liu, Yunwei Wang, Yan Li, Jian Zhang, Yu Li, Liang Luo, Yage Shang, Lixia Zhang, Yuxi Chen, Kuo Shen, Dahai Hu","doi":"10.1093/burnst/tkad064","DOIUrl":"10.1093/burnst/tkad064","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic scarring is the most serious and unmet challenge following burn and trauma injury and often leads to pain, itching and even loss of function. However, the demand for ideal scar prevention and treatment is difficult to satisfy. We aimed to discover the effects and mechanisms of adipose-derived stem cell (ADSC) exosomes in hypertrophic scarring.</p><p><strong>Methods: </strong>ADSC exosomes were isolated from the culture supernatant of ADSCs and identified by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The effect of ADSC exosomes on wound healing and scar formation was detected by the wound model of BALB/c mice. We isolated myofibroblasts from hypertrophic scar tissue and detected the cell viability, proliferation and migration of myofibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on fibrosis in myofibroblasts, we detected the expression of Smad2 in hypertrophic scar tissue and normal skin and the regulatory mechanism of ADSC exosomes on Smad2. Injection of bleomycin was performed in male BALB/c mice to establish an <i>in vivo</i> fibrosis model while ADSC exosomes were administered to observe their protective effect. The tissue injury of mice was observed via hematoxylin and eosin and Masson staining and related testing.</p><p><strong>Results: </strong>In this study, we found that ADSC exosomes could not only speed up wound healing and improve healing quality but also prevent scar formation. ADSC exosomes inhibited expression of fibrosis-related molecules such as α-smooth muscle actin, collagen I (COL1) and COL3 and inhibited the transdifferentiation of myofibroblasts. In addition, we verified that Smad2 is highly expressed in both hypertrophic scar tissue and hypertrophic fibroblasts, while ADSC exosomes downregulated the expression of Smad2 in hypertrophic fibroblasts. Further regulatory mechanism analysis revealed that microRNA-125b-5p (miR-125b-5p) is highly expressed in ADSC exosomes and binds to the 3' untranslated region of Smad2, thus inhibiting its expression. <i>In vivo</i> experiments also revealed that ADSC exosomes could alleviate bleomycin-induced skin fibrosis and downregulate the expression of Smad2.</p><p><strong>Conclusions: </strong>We found that ADSC exosomes could alleviate hypertrophic scars via the suppression of Smad2 by the specific delivery of miR-125b-5p.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 ","pages":"tkad064"},"PeriodicalIF":5.3,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sen Su, Yong Zhang, Dan Wu, Chao Wang, Jianhong Hu, Yan Wei, Xi Peng
Background Severe burn injury causes a hypermetabolic response, resulting in muscle protein catabolism and multiple organ damage syndrome. However, this response has not yet been continuously characterized by metabolomics in patients. This study aims to quantify temporal changes in the metabolic processes of patients with severe burns. Methods We employed 1H-nuclear magnetic resonance (NMR) spectroscopy to scrutinize metabolic alterations during the initial 35 days following burn injury in a cohort of 17 adult patients with severe burns, with 10 healthy individuals included as controls. Plasma specimens were collected from patients on postburn days 1, 3, 7, 14, 21, 28 and 35. After performing multivariate statistical analysis, repeated-measures analysis of variance and time-series analysis, we quantified changes in metabolite concentrations. Results Among the 36 metabolites quantified across 119 samples from burn patients, branched-chain amino acids, glutamate, glycine, glucose, pyruvate, lactate, trimethylamine N-oxide and others exhibited obvious temporal variations in concentration. Notably, these metabolites could be categorized into three clusters based on their temporal characteristics. The initial response to injury was characterized by changes in lactate and amino acids, while later changes were driven by an increase in fatty acid catabolism and microbial metabolism, leading to the accumulation of ketone bodies and microbial metabolites. Conclusions Metabolomics techniques utilizing NMR have the potential to monitor the intricate processes of metabolism in patients with severe burns. This study confirmed that the third day after burn injury serves as the boundary between the ebb phase and the flow phase. Furthermore, identification of three distinct temporal patterns of metabolites revealed the intrinsic temporal relationships between these metabolites, providing clinical data for optimizing therapeutic strategies.
{"title":"1H-nuclear magnetic resonance analysis reveals dynamic changes in the metabolic profile of patients with severe burns","authors":"Sen Su, Yong Zhang, Dan Wu, Chao Wang, Jianhong Hu, Yan Wei, Xi Peng","doi":"10.1093/burnst/tkae007","DOIUrl":"https://doi.org/10.1093/burnst/tkae007","url":null,"abstract":"Background Severe burn injury causes a hypermetabolic response, resulting in muscle protein catabolism and multiple organ damage syndrome. However, this response has not yet been continuously characterized by metabolomics in patients. This study aims to quantify temporal changes in the metabolic processes of patients with severe burns. Methods We employed 1H-nuclear magnetic resonance (NMR) spectroscopy to scrutinize metabolic alterations during the initial 35 days following burn injury in a cohort of 17 adult patients with severe burns, with 10 healthy individuals included as controls. Plasma specimens were collected from patients on postburn days 1, 3, 7, 14, 21, 28 and 35. After performing multivariate statistical analysis, repeated-measures analysis of variance and time-series analysis, we quantified changes in metabolite concentrations. Results Among the 36 metabolites quantified across 119 samples from burn patients, branched-chain amino acids, glutamate, glycine, glucose, pyruvate, lactate, trimethylamine N-oxide and others exhibited obvious temporal variations in concentration. Notably, these metabolites could be categorized into three clusters based on their temporal characteristics. The initial response to injury was characterized by changes in lactate and amino acids, while later changes were driven by an increase in fatty acid catabolism and microbial metabolism, leading to the accumulation of ketone bodies and microbial metabolites. Conclusions Metabolomics techniques utilizing NMR have the potential to monitor the intricate processes of metabolism in patients with severe burns. This study confirmed that the third day after burn injury serves as the boundary between the ebb phase and the flow phase. Furthermore, identification of three distinct temporal patterns of metabolites revealed the intrinsic temporal relationships between these metabolites, providing clinical data for optimizing therapeutic strategies.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"125 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Chronic skin wounds are a leading cause of hospital admissions and reduced life expectancy among older people and individuals with diabetes. Delayed wound healing is often attributed to a series of cellular abnormalities. Matrine, a well-studied component found in Sophora flavescens, is recognized for its anti-inflammatory effects. However, its impact on wound healing still remains uncertain. This study aims to explore the potential of matrine in promoting wound healing.
Methods: In this study, we utilized gradient extrusion to produce fibroblast-derived exosome-mimetic vesicles as carriers for matrine (MHEM). MHEM were characterized using transmission electron microscopy and dynamic light scattering analysis. The therapeutic effect of MHEM in wound healing was explored in vitro and in vivo.
Results: Both matrine and MHEM enhanced the cellular activity as well as the migration of fibroblasts and keratinocytes. The potent anti-inflammatory effect of matrine diluted the inflammatory response in the vicinity of wounds. Furthermore, MHEM worked together to promote angiogenesis and the expression of transforming growth factor β and collagen I. MHEM contained growth factors of fibroblasts that regulated the functions of fibroblasts, keratinocytes and monocytes, which synergistically promoted wound healing with the anti-inflammatory effect of matrine.
Conclusions: MHEM showed enhanced therapeutic efficacy in the inflammatory microenvironment, for new tissue formation and angiogenesis of wound healing.
{"title":"Exosome-mimetic vesicles derived from fibroblasts carrying matrine for wound healing.","authors":"Xinyue Zhang, Jiahua Huang, Jing Zhao, Lisha Li, Fengze Miao, Tingrui Zhang, Zhongjian Chen, Xing Zhou, Zongguang Tai, Quangang Zhu","doi":"10.1093/burnst/tkae015","DOIUrl":"10.1093/burnst/tkae015","url":null,"abstract":"<p><strong>Background: </strong>Chronic skin wounds are a leading cause of hospital admissions and reduced life expectancy among older people and individuals with diabetes. Delayed wound healing is often attributed to a series of cellular abnormalities. Matrine, a well-studied component found in <i>Sophora flavescens</i>, is recognized for its anti-inflammatory effects. However, its impact on wound healing still remains uncertain. This study aims to explore the potential of matrine in promoting wound healing.</p><p><strong>Methods: </strong>In this study, we utilized gradient extrusion to produce fibroblast-derived exosome-mimetic vesicles as carriers for matrine (MHEM). MHEM were characterized using transmission electron microscopy and dynamic light scattering analysis. The therapeutic effect of MHEM in wound healing was explored <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>Both matrine and MHEM enhanced the cellular activity as well as the migration of fibroblasts and keratinocytes. The potent anti-inflammatory effect of matrine diluted the inflammatory response in the vicinity of wounds. Furthermore, MHEM worked together to promote angiogenesis and the expression of transforming growth factor β and collagen I. MHEM contained growth factors of fibroblasts that regulated the functions of fibroblasts, keratinocytes and monocytes, which synergistically promoted wound healing with the anti-inflammatory effect of matrine.</p><p><strong>Conclusions: </strong>MHEM showed enhanced therapeutic efficacy in the inflammatory microenvironment, for new tissue formation and angiogenesis of wound healing.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 ","pages":"tkae015"},"PeriodicalIF":5.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai-xuan Dong, Ya Zhou, Yao-yu Cheng, Hao-tian Luo, Jia-zhang Duan, Xi Yang, Yong-qing Xu, Sheng Lu, Xiao-qing He
Background It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13–27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.
背景用传统皮瓣修复宽大或不规则的缺损具有挑战性，而大腿前外侧（ALT）分叶状穿孔器皮瓣是修复此类缺损的理想选择。然而，穿孔器有很多变异，因此良好的术前规划非常重要。本研究试图探讨数字化技术在使用 ALT 分叶状穿孔器皮瓣修复四肢复杂软组织缺损中的可行性和临床效果。方法 对28例四肢复杂软组织缺损患者进行计算机断层扫描（CTA），并将CTA数据以DICOM格式导入Mimics 20.0软件。根据股外侧环动脉的穿孔情况和肢体缺损的大小，选择一条大腿上有两条或两条以上来自同一源血管的穿孔，进行ALT分叶穿孔皮瓣模型的三维重建。术前使用 Mimics 20.0 软件可视化血管解剖、虚拟设计和皮瓣切除。术中设计和切除 ALT 分叶状穿孔器皮瓣均以术前数字化设计为指导，并记录实际解剖观察和测量结果。结果 所有患者在术前都成功进行了数字化重建；重建动态显示了皮瓣血管的解剖结构，并在手术中准确指导了皮瓣的设计和切除。切除皮瓣的参数与术前参数一致。7名患者出现了术后并发症，但所有皮瓣均顺利存活。所有供体部位均直接闭合。所有患者均接受了 13-27 个月（平均 19.75 个月）的随访。每个皮瓣的颜色和质地都令人满意，每个供体部位都显示出线状疤痕。结论 数字化技术可以有效、精确地辅助设计和采集 ALT 分叶状穿孔器皮瓣，为个体化评估和皮瓣设计提供有效方法，并降低手术风险和难度。
{"title":"Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs","authors":"Kai-xuan Dong, Ya Zhou, Yao-yu Cheng, Hao-tian Luo, Jia-zhang Duan, Xi Yang, Yong-qing Xu, Sheng Lu, Xiao-qing He","doi":"10.1093/burnst/tkae011","DOIUrl":"https://doi.org/10.1093/burnst/tkae011","url":null,"abstract":"Background It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13–27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"19 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07eCollection Date: 2024-01-01DOI: 10.1093/burnst/tkae005
David R Schieffelers, Tianfeng Ru, Haonan Dai, Ziqing Ye, Eric van Breda, Ulrike Van Daele, Weiguo Xie, Jun Wu
Background: Despite being a stable component of burn rehabilitation at later stages of recovery, exercise training is not commonly provided during the acute phase of burns. A lack of evidence surrounding its efficacy and safety in severely burned adults has hampered its implementation in acute burn care. The aim of this study was to investigate the capacity of early exercise training to modulate parameters of postburn muscle wasting and quality of life.
Methods: Adults <65 years of age with burns ≥40% total burn surface area (TBSA) were randomly allocated to either receive early exercise (n = 29) in addition to standard care or standard care alone (n = 29). Early exercise involved resistance and aerobic training, which commenced as early as possible and lasted for a duration of 6 to 12 weeks, in line with burn center length of stay. Ultrasound-derived quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA), lower limb muscle force, Eurocol Quality of Life-5 Dimensions and Burn Specific Health Scale Brief (BSHS-B) were assessed 6 and 12 weeks after baseline. Mixed models were fitted to compare between-group changes over time.
Results: A total of 58 adults [42 (95% confidence interval 40-45) years old; 40-94% TBSA range, 86% previously mechanically ventilated] participated in this study. Exercise commenced 7 days [IQR (interquartile range) 5-9] after burn center admission with an attendance rate of 93%. Allocation to the exercise group had a protective effect on the loss of muscle size from baseline to 6 weeks of follow-up (QMLT: β-coefficient: 0.05 cm, p = 0.010; RF-CSA: β-coefficient: 0.05 cm2, p = 0.045), and resulted in an improved recovery from 6 to 12 weeks (QMLT: β-coefficient: 0.04 cm, p = 0.01; RF-CSA: β-coefficient: 0.06 cm2, p < 0.001). Muscle force increased significantly more in the exercise group than in the control group (β-coefficient: 3.102 N, p < 0.001) between 6 and 12 weeks. Besides a marginally significant effect for the BSHS-B domains 'affect' and 'interpersonal relationships' between 6 and 12 weeks, no benefits were observed in the other assessed quality-of-life measures. No serious adverse events were reported in the exercise group.
Conclusions: The results of this study support the use of early exercise training as a feasible and efficacious therapeutic strategy to manage burn-related changes in muscle size and strength in adults with acute severe burn injury.
{"title":"Effects of early exercise training following severe burn injury: a randomized controlled trial.","authors":"David R Schieffelers, Tianfeng Ru, Haonan Dai, Ziqing Ye, Eric van Breda, Ulrike Van Daele, Weiguo Xie, Jun Wu","doi":"10.1093/burnst/tkae005","DOIUrl":"10.1093/burnst/tkae005","url":null,"abstract":"<p><strong>Background: </strong>Despite being a stable component of burn rehabilitation at later stages of recovery, exercise training is not commonly provided during the acute phase of burns. A lack of evidence surrounding its efficacy and safety in severely burned adults has hampered its implementation in acute burn care. The aim of this study was to investigate the capacity of early exercise training to modulate parameters of postburn muscle wasting and quality of life.</p><p><strong>Methods: </strong>Adults <65 years of age with burns ≥40% total burn surface area (TBSA) were randomly allocated to either receive early exercise (n = 29) in addition to standard care or standard care alone (n = 29). Early exercise involved resistance and aerobic training, which commenced as early as possible and lasted for a duration of 6 to 12 weeks, in line with burn center length of stay. Ultrasound-derived quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA), lower limb muscle force, Eurocol Quality of Life-5 Dimensions and Burn Specific Health Scale Brief (BSHS-B) were assessed 6 and 12 weeks after baseline. Mixed models were fitted to compare between-group changes over time.</p><p><strong>Results: </strong>A total of 58 adults [42 (95% confidence interval 40-45) years old; 40-94% TBSA range, 86% previously mechanically ventilated] participated in this study. Exercise commenced 7 days [IQR (interquartile range) 5-9] after burn center admission with an attendance rate of 93%. Allocation to the exercise group had a protective effect on the loss of muscle size from baseline to 6 weeks of follow-up (QMLT: β-coefficient: 0.05 cm, <i>p</i> = 0.010; RF-CSA: β-coefficient: 0.05 cm<sup>2</sup>, <i>p</i> = 0.045), and resulted in an improved recovery from 6 to 12 weeks (QMLT: β-coefficient: 0.04 cm, <i>p</i> = 0.01; RF-CSA: β-coefficient: 0.06 cm<sup>2</sup>, <i>p</i> < 0.001). Muscle force increased significantly more in the exercise group than in the control group (β-coefficient: 3.102 N, <i>p</i> < 0.001) between 6 and 12 weeks. Besides a marginally significant effect for the BSHS-B domains 'affect' and 'interpersonal relationships' between 6 and 12 weeks, no benefits were observed in the other assessed quality-of-life measures. No serious adverse events were reported in the exercise group.</p><p><strong>Conclusions: </strong>The results of this study support the use of early exercise training as a feasible and efficacious therapeutic strategy to manage burn-related changes in muscle size and strength in adults with acute severe burn injury.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 ","pages":"tkae005"},"PeriodicalIF":5.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06eCollection Date: 2024-01-01DOI: 10.1093/burnst/tkae006
Mingzheng Wu, Bobin Mi, Liu Liu, Haoli Ma, Cheng Jiang, Shan Jiang, Yulin Li, Yan Zhao
Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.
{"title":"Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.","authors":"Mingzheng Wu, Bobin Mi, Liu Liu, Haoli Ma, Cheng Jiang, Shan Jiang, Yulin Li, Yan Zhao","doi":"10.1093/burnst/tkae006","DOIUrl":"10.1093/burnst/tkae006","url":null,"abstract":"<p><p>Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 ","pages":"tkae006"},"PeriodicalIF":5.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lanjuan Xu, Tingting An, Baohui Jia, Qiong Wu, Jinggui Shen, Jie Jin, Jing Liu, Chengjian Li
Background Oxidative stress (OS) and inflammatory reactions play pivotal roles in secondary brain injury after traumatic brain injury (TBI). Histone deacetylase 3 (HDAC3) controls the acetylation of histones and non-histones, which has a significant impact on the central nervous system’s reaction to damage. This research determined the implications of RGFP966, a new and specific inhibitor of HDAC3, for the antioxidant (AO) systems mediated by nuclear factor erythroid2-related factor 2 (Nrf2) and the Nod-like receptor protein 3 (NLRP3) inflammasome in TBI. The study also studied the underlying mechanisms of RGFP966’s actions. Our objective was to examine the impacts and underlying RGFP966 mechanisms in TBI. Methods In vitro, a rat cortical neuron OS model was induced by H2O2, followed by the addition of RGFP966 to the culture medium. Neurons were collected after 24 h for western blot (WB), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 2′-7′-dichlorodihydrofluorescein diacetate staining. In vivo, RGFP966 (10 mg/kg) was administered post-TBI. Brain tissue water content and modified neurological severity scores were assessed 72 h post-injury. Cortical tissues surrounding the focal injury were subjected to western blot, TUNEL staining, Nissl staining and immunofluorescence/immunohistochemistry staining, and malondialdehyde level, hindered glutathione content and superoxide dismutase activity were measured. Serum was collected for the enzyme-linked immunosorbent assay. Nrf2-specific shRNA lentivirus was injected into the lateral ventricle of rats for 7 days, and cerebral cortex tissue was analyzed by WB and real-time polymerase chain reaction. Results During in vitro and in vivo experiments, RGFP966 suppressed HDAC3 expression, promoted Nrf2 nuclear translocation, activated downstream AO enzymes, mitigated excessive reactive oxygen species production and alleviated nerve cell apoptosis. RGFP966 effectively reduced brain edema and histological damage and enhanced neurological and cognitive function in rats with TBI. RGFP966 markedly inhibited NLRP3 inflammasome activation mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4). Nrf2 knockdown in TBI rats attenuated the AO and anti-inflammatory, neuroprotective impacts of RGFP966. Conclusions Overall, our findings demonstrate that RGFP966 can mitigate the first brain damage and neurological impairments in TBI. The underlying mechanism involves triggering the Nrf2-mediated AO system and negatively regulating the HMGB1/TLR4-mediated NLRP3 inflammasome pathway.
{"title":"Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway","authors":"Lanjuan Xu, Tingting An, Baohui Jia, Qiong Wu, Jinggui Shen, Jie Jin, Jing Liu, Chengjian Li","doi":"10.1093/burnst/tkad062","DOIUrl":"https://doi.org/10.1093/burnst/tkad062","url":null,"abstract":"Background Oxidative stress (OS) and inflammatory reactions play pivotal roles in secondary brain injury after traumatic brain injury (TBI). Histone deacetylase 3 (HDAC3) controls the acetylation of histones and non-histones, which has a significant impact on the central nervous system’s reaction to damage. This research determined the implications of RGFP966, a new and specific inhibitor of HDAC3, for the antioxidant (AO) systems mediated by nuclear factor erythroid2-related factor 2 (Nrf2) and the Nod-like receptor protein 3 (NLRP3) inflammasome in TBI. The study also studied the underlying mechanisms of RGFP966’s actions. Our objective was to examine the impacts and underlying RGFP966 mechanisms in TBI. Methods In vitro, a rat cortical neuron OS model was induced by H2O2, followed by the addition of RGFP966 to the culture medium. Neurons were collected after 24 h for western blot (WB), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 2′-7′-dichlorodihydrofluorescein diacetate staining. In vivo, RGFP966 (10 mg/kg) was administered post-TBI. Brain tissue water content and modified neurological severity scores were assessed 72 h post-injury. Cortical tissues surrounding the focal injury were subjected to western blot, TUNEL staining, Nissl staining and immunofluorescence/immunohistochemistry staining, and malondialdehyde level, hindered glutathione content and superoxide dismutase activity were measured. Serum was collected for the enzyme-linked immunosorbent assay. Nrf2-specific shRNA lentivirus was injected into the lateral ventricle of rats for 7 days, and cerebral cortex tissue was analyzed by WB and real-time polymerase chain reaction. Results During in vitro and in vivo experiments, RGFP966 suppressed HDAC3 expression, promoted Nrf2 nuclear translocation, activated downstream AO enzymes, mitigated excessive reactive oxygen species production and alleviated nerve cell apoptosis. RGFP966 effectively reduced brain edema and histological damage and enhanced neurological and cognitive function in rats with TBI. RGFP966 markedly inhibited NLRP3 inflammasome activation mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4). Nrf2 knockdown in TBI rats attenuated the AO and anti-inflammatory, neuroprotective impacts of RGFP966. Conclusions Overall, our findings demonstrate that RGFP966 can mitigate the first brain damage and neurological impairments in TBI. The underlying mechanism involves triggering the Nrf2-mediated AO system and negatively regulating the HMGB1/TLR4-mediated NLRP3 inflammasome pathway.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiqiong Liu, Huanhuan Gao, Huating Chen, Shuaifei Ji, Lu Wu, Hongliang Zhang, Yujia Wang, Xiaobing Fu, Xiaoyan Sun
Sebaceous glands (SGs), as holocrine-secreting appendages, lubricate the skin and play a central role in the skin barrier. Large full-thickness skin defects cause overall architecture disruption and SG loss. However, an effective strategy for SG regeneration is lacking. Organoids are 3D multicellular structures that replicate key anatomical and functional characteristics of in vivo tissues and exhibit great potential in regenerative medicine. Recently, considerable progress has been made in developing reliable procedures for SG organoids and existing SG organoids recapitulate the main morphological, structural and functional features of their in vivo counterparts. Engineering approaches empower researchers to manipulate cell behaviors, the surrounding environment and cell–environment crosstalk within the culture system as needed. These techniques can be applied to the SG organoid culture system to generate functionally more competent SG organoids. This review aims to provide an overview of recent advancements in SG organoid engineering. It highlights some potential strategies for SG organoid functionalization that are promising to forge a platform for engineering vascularized, innervated, immune-interactive and lipogenic SG organoids. We anticipate that this review will not only contribute to improving our understanding of SG biology and regeneration but also facilitate the transition of the SG organoid from laboratory research to a feasible clinical application.
{"title":"Sebaceous gland organoid engineering","authors":"Yiqiong Liu, Huanhuan Gao, Huating Chen, Shuaifei Ji, Lu Wu, Hongliang Zhang, Yujia Wang, Xiaobing Fu, Xiaoyan Sun","doi":"10.1093/burnst/tkae003","DOIUrl":"https://doi.org/10.1093/burnst/tkae003","url":null,"abstract":"Sebaceous glands (SGs), as holocrine-secreting appendages, lubricate the skin and play a central role in the skin barrier. Large full-thickness skin defects cause overall architecture disruption and SG loss. However, an effective strategy for SG regeneration is lacking. Organoids are 3D multicellular structures that replicate key anatomical and functional characteristics of in vivo tissues and exhibit great potential in regenerative medicine. Recently, considerable progress has been made in developing reliable procedures for SG organoids and existing SG organoids recapitulate the main morphological, structural and functional features of their in vivo counterparts. Engineering approaches empower researchers to manipulate cell behaviors, the surrounding environment and cell–environment crosstalk within the culture system as needed. These techniques can be applied to the SG organoid culture system to generate functionally more competent SG organoids. This review aims to provide an overview of recent advancements in SG organoid engineering. It highlights some potential strategies for SG organoid functionalization that are promising to forge a platform for engineering vascularized, innervated, immune-interactive and lipogenic SG organoids. We anticipate that this review will not only contribute to improving our understanding of SG biology and regeneration but also facilitate the transition of the SG organoid from laboratory research to a feasible clinical application.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"28 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel Hundeshagen, Elisabeth Blears, Viktoria Mertin, Andrew G Day, Alen Palackic, Christian Tapking, Valentin Haug, Ulrich Kneser, Björn Bliesener, Adriana C Panayi, Ariel Aballay, Francois Depret, Christian Stoppe, Daren K Heyland
Background Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47–0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28–0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24–0.82, p = 0.01). Conclusions The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.
{"title":"Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial","authors":"Gabriel Hundeshagen, Elisabeth Blears, Viktoria Mertin, Andrew G Day, Alen Palackic, Christian Tapking, Valentin Haug, Ulrich Kneser, Björn Bliesener, Adriana C Panayi, Ariel Aballay, Francois Depret, Christian Stoppe, Daren K Heyland","doi":"10.1093/burnst/tkad063","DOIUrl":"https://doi.org/10.1093/burnst/tkad063","url":null,"abstract":"Background Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47–0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28–0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24–0.82, p = 0.01). Conclusions The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"48 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.
{"title":"Acne-induced pathological scars: pathophysiology and current treatments","authors":"Wanyu Xu, Dorsa Gholamali Sinaki, Yuchen Tang, Yunsheng Chen, Yixin Zhang, Zheng Zhang","doi":"10.1093/burnst/tkad060","DOIUrl":"https://doi.org/10.1093/burnst/tkad060","url":null,"abstract":"Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"69 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140533918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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