Objective: To systematically explore the effects of moderate-intensity static magnetic fields (SMF) on type 2 diabetic wound healing and preliminarily explore the possible mechanism, and hence to lay a foundation for ...Objective: To systematically explore the effects of moderate-intensity static magnetic fields (SMF) on type 2 diabetic wound healing and preliminarily explore the possible mechanism, and hence to lay a foundation for its scientific and extensive clinical application. Methods:Round-shape wound of soft tissues with 1-cm diameter was constructed on the dorsum of thirty-two 3-month-old male type 2 diabetic db/db mice and sixteen wild-type mice with the same gene background, followed by covered with transparent film wound dressing. The experiment was divided into the control group (control), db/db mice group (db/db), and db/db mice exposed to SMF group (db/db+SMF) with sixteen mice in each group. Four mice in each group were killed post 5, 12 and 19 days of the wound model establishment, respectively. The mice in the db/db+SMF group were subjected to systemic SMF exposure (4 mT peak intensity) with 2 h per day. The wound closure rate, overall wound healing period, tensile strength, and histopathological morphology in each group were determined and analyzed. The interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) gene expression were also measured and analyzed. Results: SMF significantly increased the wound closure rate (P<0.05), decreased the overall healing period (P<0.05), increased the tensile strength of wound tissues (P<0.05), decreased the number of inflammatory cells, and inhibited the expression of inflammatory cytokines (IL-1β, TNF-αand IL-6) in db/db mice at 5, 12 and 19 days post-surgery (P<0.05), whereas SMF had no significant effect on the VEGF expression. Conclusion: Moderate-intensity systemic SMF exposure exhibits positive therapeutic effects on accelerating type 2 diabetic soft tissue wound repair, and the positive effects are closely related to its significant anti-inflammatory response.展开更多
High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the h...High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed in- creasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.展开更多
BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our...BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our previous studies have shown that bone marrow mesenchymal stem cells(BMSCs)promote uterine damage repair,the underlying mechanisms remain unclear.However,exploring the specific regulatory roles of BMSCs in uterine injury treatment is crucial for further understanding their functions and enhancing therapeutic efficacy.AIM To investigate the underlying mechanism by which BMSCs promote the process of uterine healing.METHODS In in vivo experiments,we established a model of full-thickness uterine injury and injected BMSCs into the uterine wound.Transcriptome sequencing was per-formed to determine the enrichment of differentially expressed genes at the wound site.In in vitro experiments,we isolated rat uterine smooth muscle cells(USMCs)and cocultured them with BMSCs to observe the interaction between BMSCs and USMCs in the microenvironment.RESULTS We found that the differentially expressed genes were mainly related to cell growth,tissue repair,and angiogenesis,while the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was highly enriched.Quantitative reverse-transcription polymerase chain reaction was used to validate differentially expressed genes,and the results demonstrated that BMSCs can upregulate genes related to regeneration and downregulate genes related to inflammation.Coculturing BMSCs promoted the migration and proliferation of USMCs,and the USMC microenvironment promoted the myogenic differentiation of BMSCs.Finally,we validated the PI3K/AKT pathway in tissues and cells and showed that BMSCs activate the PI3K/AKT pathway to promote the regeneration of uterine smooth muscle both in vivo and in vitro.CONCLUSION BMSCs upregulated uterine wound regeneration and anti-inflammatory factors and enhanced uterine smooth muscle proliferation through the PI3K/AKT pathway both in vivo and in vitro.展开更多
Objective: To explore an early stage repair method for soft tissue defect of limbs of modern firearm wound, and to improve treating result. Methods: Defects of the hind limbs of dogs were repaired with skin, muscle an...Objective: To explore an early stage repair method for soft tissue defect of limbs of modern firearm wound, and to improve treating result. Methods: Defects of the hind limbs of dogs were repaired with skin, muscle and myocutaneous flaps. Results: Wounds healed within 2 weeks in the experimental group except one that healed in 3 weeks because of infection. Limb function was close to normal. The treatment result was better in the experimental group than the control. Conclusions: Skin, muscle and myocutaneous flaps can cover soft tissue defect at an early stage, prevent and reduce infection, promote the healing and recovery of combined injury, reduce the time of treatment and disability rate.展开更多
In the long history of the Chinese nation,traditional Chinese medicine has made great contributions to the protection of the health of the Chinese people.Given that many pathological processes can cause tissue damage,...In the long history of the Chinese nation,traditional Chinese medicine has made great contributions to the protection of the health of the Chinese people.Given that many pathological processes can cause tissue damage,does Chinese medicine also promote tissue regeneration in the process of disease recovery?It has been found from recent research articles that traditional Chinese medicine can promote tissue regeneration in the treatment of diseases.The following is an illustration of the role of Chinese medicine in selected parts of the study.展开更多
背景:铁死亡介导的缺血再灌注损伤对压疮的发生发展起重要作用,可能存在压疮相关的铁死亡生物标志物,但其机制尚未阐明。目的:通过生物信息学手段探讨压疮的分子机制,寻找压疮过程中铁死亡相关差异基因,为其临床治疗提供新的视角。方法...背景:铁死亡介导的缺血再灌注损伤对压疮的发生发展起重要作用,可能存在压疮相关的铁死亡生物标志物,但其机制尚未阐明。目的:通过生物信息学手段探讨压疮的分子机制,寻找压疮过程中铁死亡相关差异基因,为其临床治疗提供新的视角。方法:使用GEO数据库和FerrDb数据库下载数据集并进行预处理。对单细胞转录组测序数据进行聚类和占比分析、代谢活性和拟时序分析、细胞通讯分析、铁死亡基因集细胞识别和富集分析,确定铁死亡差异基因,并通过动物实验进一步验证。将20只SD大鼠随机分为正常组和模型组,每组10只。正常组大鼠不进行任何处理,模型组大鼠采用缺血再灌注循环周期模式制备压疮大鼠模型,采用荧光定量PCR和免疫印迹检测压疮大鼠创面组织内差异表达基因和蛋白的变化。结果与结论:(1)单细胞转录组测序数据聚类划分为6种细胞类型,压疮组2型和3型角质形成细胞占比较高。(2)不同细胞亚群之间具有明显的代谢异质性和演变轨迹。(3)2型和3型角质形成细胞在细胞通讯中作用最强,2型角质形成细胞配体-受体强度最佳。(4)2型角质形成细胞铁死亡得分较高,有显著上调或下调的差异基因,并得到27个GO富集条目、20个KEGG富集条目和24个铁死亡相关差异基因,以谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)和长链酯酰辅酶A合成酶4(acyl-CoA synthetase long chain family member 4,ACSL4)为主。(5)动物实验验证了与正常组相比,模型组大鼠铁死亡抑制蛋白GPX4表达下调,铁死亡促进蛋白ACSL4表达上调。上述结果证实,压疮组织中存在铁死亡,GPX4和ACSL4为调控压疮组织中铁死亡的重要基因。展开更多
基金This study was supported by the General Project of National Natural Science Foundation of China (Grant 81471806)
文摘Objective: To systematically explore the effects of moderate-intensity static magnetic fields (SMF) on type 2 diabetic wound healing and preliminarily explore the possible mechanism, and hence to lay a foundation for its scientific and extensive clinical application. Methods:Round-shape wound of soft tissues with 1-cm diameter was constructed on the dorsum of thirty-two 3-month-old male type 2 diabetic db/db mice and sixteen wild-type mice with the same gene background, followed by covered with transparent film wound dressing. The experiment was divided into the control group (control), db/db mice group (db/db), and db/db mice exposed to SMF group (db/db+SMF) with sixteen mice in each group. Four mice in each group were killed post 5, 12 and 19 days of the wound model establishment, respectively. The mice in the db/db+SMF group were subjected to systemic SMF exposure (4 mT peak intensity) with 2 h per day. The wound closure rate, overall wound healing period, tensile strength, and histopathological morphology in each group were determined and analyzed. The interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) gene expression were also measured and analyzed. Results: SMF significantly increased the wound closure rate (P<0.05), decreased the overall healing period (P<0.05), increased the tensile strength of wound tissues (P<0.05), decreased the number of inflammatory cells, and inhibited the expression of inflammatory cytokines (IL-1β, TNF-αand IL-6) in db/db mice at 5, 12 and 19 days post-surgery (P<0.05), whereas SMF had no significant effect on the VEGF expression. Conclusion: Moderate-intensity systemic SMF exposure exhibits positive therapeutic effects on accelerating type 2 diabetic soft tissue wound repair, and the positive effects are closely related to its significant anti-inflammatory response.
文摘High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed in- creasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.
基金support from the“111 program”of Ministry of Education of China and State Administration of Foreign Experts Affairs of China.
文摘BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our previous studies have shown that bone marrow mesenchymal stem cells(BMSCs)promote uterine damage repair,the underlying mechanisms remain unclear.However,exploring the specific regulatory roles of BMSCs in uterine injury treatment is crucial for further understanding their functions and enhancing therapeutic efficacy.AIM To investigate the underlying mechanism by which BMSCs promote the process of uterine healing.METHODS In in vivo experiments,we established a model of full-thickness uterine injury and injected BMSCs into the uterine wound.Transcriptome sequencing was per-formed to determine the enrichment of differentially expressed genes at the wound site.In in vitro experiments,we isolated rat uterine smooth muscle cells(USMCs)and cocultured them with BMSCs to observe the interaction between BMSCs and USMCs in the microenvironment.RESULTS We found that the differentially expressed genes were mainly related to cell growth,tissue repair,and angiogenesis,while the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was highly enriched.Quantitative reverse-transcription polymerase chain reaction was used to validate differentially expressed genes,and the results demonstrated that BMSCs can upregulate genes related to regeneration and downregulate genes related to inflammation.Coculturing BMSCs promoted the migration and proliferation of USMCs,and the USMC microenvironment promoted the myogenic differentiation of BMSCs.Finally,we validated the PI3K/AKT pathway in tissues and cells and showed that BMSCs activate the PI3K/AKT pathway to promote the regeneration of uterine smooth muscle both in vivo and in vitro.CONCLUSION BMSCs upregulated uterine wound regeneration and anti-inflammatory factors and enhanced uterine smooth muscle proliferation through the PI3K/AKT pathway both in vivo and in vitro.
文摘Objective: To explore an early stage repair method for soft tissue defect of limbs of modern firearm wound, and to improve treating result. Methods: Defects of the hind limbs of dogs were repaired with skin, muscle and myocutaneous flaps. Results: Wounds healed within 2 weeks in the experimental group except one that healed in 3 weeks because of infection. Limb function was close to normal. The treatment result was better in the experimental group than the control. Conclusions: Skin, muscle and myocutaneous flaps can cover soft tissue defect at an early stage, prevent and reduce infection, promote the healing and recovery of combined injury, reduce the time of treatment and disability rate.
文摘In the long history of the Chinese nation,traditional Chinese medicine has made great contributions to the protection of the health of the Chinese people.Given that many pathological processes can cause tissue damage,does Chinese medicine also promote tissue regeneration in the process of disease recovery?It has been found from recent research articles that traditional Chinese medicine can promote tissue regeneration in the treatment of diseases.The following is an illustration of the role of Chinese medicine in selected parts of the study.
文摘背景:铁死亡介导的缺血再灌注损伤对压疮的发生发展起重要作用,可能存在压疮相关的铁死亡生物标志物,但其机制尚未阐明。目的:通过生物信息学手段探讨压疮的分子机制,寻找压疮过程中铁死亡相关差异基因,为其临床治疗提供新的视角。方法:使用GEO数据库和FerrDb数据库下载数据集并进行预处理。对单细胞转录组测序数据进行聚类和占比分析、代谢活性和拟时序分析、细胞通讯分析、铁死亡基因集细胞识别和富集分析,确定铁死亡差异基因,并通过动物实验进一步验证。将20只SD大鼠随机分为正常组和模型组,每组10只。正常组大鼠不进行任何处理,模型组大鼠采用缺血再灌注循环周期模式制备压疮大鼠模型,采用荧光定量PCR和免疫印迹检测压疮大鼠创面组织内差异表达基因和蛋白的变化。结果与结论:(1)单细胞转录组测序数据聚类划分为6种细胞类型,压疮组2型和3型角质形成细胞占比较高。(2)不同细胞亚群之间具有明显的代谢异质性和演变轨迹。(3)2型和3型角质形成细胞在细胞通讯中作用最强,2型角质形成细胞配体-受体强度最佳。(4)2型角质形成细胞铁死亡得分较高,有显著上调或下调的差异基因,并得到27个GO富集条目、20个KEGG富集条目和24个铁死亡相关差异基因,以谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)和长链酯酰辅酶A合成酶4(acyl-CoA synthetase long chain family member 4,ACSL4)为主。(5)动物实验验证了与正常组相比,模型组大鼠铁死亡抑制蛋白GPX4表达下调,铁死亡促进蛋白ACSL4表达上调。上述结果证实,压疮组织中存在铁死亡,GPX4和ACSL4为调控压疮组织中铁死亡的重要基因。