生长激素在创面愈合中的应用

软组织损伤创面在合并糖尿病、放射治疗等情况下,常常延迟愈合、不愈、或反复发作,转变为慢性难愈性创面,成为长期困扰,临床治疗的一大难题。通常采用的皮肤移植疗法,无论自体还是异体皮都受到供体来源少的限制,异体皮和人工合成皮还存在免疫排斥等问题。生长激素在慢性创面愈合中的作用受到广泛关注,为慢性难愈创面的治疗提供了新的途径,有望带来突破性的治疗效果。     

细菌生物膜形成与慢性难愈性创面相关性的研究进展

感染是影响慢性难愈性创面愈合最常见的原因,由于多种细菌混合感染、耐药性产生、生物膜的形成使其治疗成为难题.其中,细菌生物膜形成是导致创面的难以愈合的重要因素之一.本文就慢性难愈合创面中细菌生物膜的形成机制、特征、生态学、对伤口愈合的影响以及可能的治疗对策等作一综述.     

树突状表皮T淋巴细胞对糖尿病小鼠创面的治疗效果

目的建立体外大量扩增高纯度小鼠树突状表皮T淋巴细胞(DETCs)培养技术,并证实外源性给予DETCs能够有效促进糖尿病小鼠创面愈合。方法通过流式细胞技术及Western Blot方法分析糖尿病及正常小鼠表皮组织中DETCs比例和IGF-1/KGF-1表达情况。体外培养扩增获得大量高纯度DETCs后,局部植入糖尿病创缘皮下,创面未愈合面积采用单因素方差分析,通过图像分析软件Image-pro plus分别统计每组5只糖尿病小鼠每天创面面积与红色标尺面积之比数据统计分析。结果对比正常小鼠,糖尿病表皮组织中DETCs比例和IGF-1/KGF-1表达均显著降低;体外培养能够获得大量高纯度DETCs(95﹪);创缘局部植入DETCs后能够显著增强糖尿病创缘皮肤表皮组织IGF-1/KGF-1的表达,并从第2天,对照组创面面积与红色标尺面积比为0.769±0.034,实验组创面面积与红色标尺面积比为0.692±0.038,到第7天对照组创面面积与红色标尺面积比为0.178±0.024,实验组创面面积与红色标尺面积比为0.011±0.003,实验组创面比对照组创面愈合面积显著加速。结论外源性给予DETCs能够显著改善糖尿病创面愈合,可能为临床糖尿病难愈创面治疗提供新的思路。     

VSD联合金因肽治疗手足外科难愈性伤口的临床研究

目的:观察封闭式负压引流技术(VSD)联合金因肽治疗手足外科难愈性伤口的临床疗效,为临床联合运用提供依据。方法:86例手足外科难愈性伤口患者随机分为治疗组和对照组各43例,治疗组采用VSD联合金因肽治疗,对照组采用常规换药治疗,观察两组临床疗效和上皮化时间、愈合时间、创面愈合率、换药次数、伤口疼痛评分、住院费用差异。结果:治疗组总有效率90.70%;对照组总有效率72.09%;两组比较,有显著性差异(P0.05);治疗组上皮化时间、愈合时间、创面愈合率、换药次数、伤口疼痛评分、住院费用较对照组相比明显缩短,差异有统计学意义(P0.05)。结论:VSD联合金因肽治疗手足外科难愈性伤口疗效确切,能更好促进损伤组织的修复,加速创面愈合,值得临床推广应用。     

蛆虫清创疗法在难愈性感染创面的临床应用

蛆虫治疗感染创面已有近千年的历史,始载于《本草纲目》,具有良好的疗效。20世纪40年代以后,随着抗生素的广泛使用,蛆虫治疗感染创面的方法逐渐被遗弃。但是随着抗生素的滥用,以及细菌严重耐药性的出现,使得人们开始重新审视这种古老而又充满生机的方法。在难愈性感染创面的治疗过程中,蛆虫通过多种作用机制能够促进创面的愈合,清除大量的坏死组织,促进肉芽组织生长,并有显著的抑菌作用。蛆虫通过多种作用机制协同作用能够促进难愈性感染伤口的愈合,值得进一步的临床研究及推广。本文广泛查阅近年国内外相关文献进行回顾与综合分析。对蛆虫清创疗法在难愈性感染创面的临床应用进行综述。     

老年难愈性创面患者临床特征及创面细菌学分析

目的分析老年难愈性创面患者的临床特征、创面细菌学及疗效,为临床治疗提供参考依据。方法回顾性分析我科2012年1月至2017年12月收治的114例老年难愈性创面患者的临床资料。对患者合并内科基础疾病、生理机能状况、创面病因和部位、创面分泌物细菌和多重耐药菌分布、创面治疗效果等进行分析。结果患者常见内科基础疾病有高血压(63例)、糖尿病(42例)、脑血管疾病(38例)和心脏病(31例),常见生理指标异常为白蛋白降低(89例)和贫血(70例)。本组共有186处创面(37例患者有1个以上创面),常见病因为烧伤(44.62%)、压迫(35.48%),常见病变部位为下肢(67.74%)。创面分离出病原菌113株,革兰阴性菌占71.68%。常见菌为铜绿假单胞菌(35.40%)、金黄色葡萄球菌(25.66%)、大肠埃希菌(12.39%)。多重耐药菌检出率为71.68%(81/113)。本组创面的治疗效果为:治愈94处、好转64处、未愈28处。38.17%创面进行了手术治疗。手术治疗的疗效为治愈58处、好转10处、未愈3处,明显优于非手术治疗(Z=-6.478,P=0.000)。结论老年难愈性创面患者合并内科基础病多、生理机能状况差,创面细菌以革兰阴性球菌为主、多重耐药菌比例高,创面治疗效果偏差,手术比例低,但手术治疗取得了较好疗效。     

烧伤病房难愈性创面病原菌分布及耐药性分析

目的 分析烧伤病房难愈性创面病原菌分布及耐药性,为临床合理选用抗生素提供依据.方法 对2006年1月至2012年6月间中国人民解放军第八五医院烧伤病房收治的难愈性创面患者创面分离出的病原菌,采用K-B纸片扩散法进行药物敏感试验,分析病原菌耐药性.结果 分离出病原菌154株,革兰阳性菌62株,占40.26％;革兰阴性菌92株,占59.74％.常见病原菌为金黄色葡萄球菌、铜绿假单胞菌和鲍曼不动杆菌.烧伤难愈性创面中金黄色葡萄球菌最多见,压迫性溃疡创面中常见铜绿假单胞菌和鲍曼不动杆菌,其他难愈性创面中铜绿假单胞菌最常见.创面革兰阳性菌对利奈唑烷和呋喃妥因的耐药率较低,革兰阴性菌对头孢哌酮/舒巴坦、阿米卡星、亚胺培南、氨曲南和头孢西丁的耐药率较低,无万古霉素耐药菌.常见病原菌中金黄色葡萄球菌和鲍曼不动杆菌的耐药率较高,铜绿假单胞菌的耐药率较低.结论 不同病因的难愈性创面病原菌分布不同,引起难愈性创面的病原菌主要为多重耐药金黄色葡萄球菌和鲍曼不动杆菌.     

创面分泌物病原菌的分布及危险因素分析

目的分析烧伤外科患者创面分泌物病原菌的分布及感染危险因素,为临床防控提供理论依据。方法采用回顾性分析方法,收集2012年至2014年期间本院烧伤外科住院患者的临床细菌学资料,分析创面病原菌的分布。根据创面分泌物细菌培养结果分为病原菌阴性组和阳性组,对比两组患者临床资料,分析创面分泌物病原菌阳性的相关危险因素,并采用非条件Logistic回归法分析独立危险因素。结果创面分泌物培养401次,阳性结果302次(75.31%)。分离出315株病原菌,其中革兰阳性菌148株(46.98%),革兰阴性菌167株(53.02%)。常见病原菌为:金黄色葡萄球菌(37.46%)、铜绿假单胞菌(23.81%)、大肠埃希菌(8.89%)、粪肠球菌(5.08%)、肺炎克雷伯杆菌(5.08%)。255例患者纳入研究,其中创面分泌物病原菌阴性组92例(36.08%),阳性组163例(63.92%)。单因素分析显示:住院史、危重症、创面深度、难愈性创面、血红蛋白、近期导管植入、近期输液、近期手术、近期抗菌药物治疗是创面分泌物病原菌阳性的相关危险因素(P0.05)。多因素Logistic回归分析显示:难愈性创面和近期抗菌药物治疗是创面分泌物病原菌阳性的独立危险因素(P0.05)。结论创面分泌物病原菌分布广泛,金黄色葡萄球菌和铜绿假单胞菌是常见菌。难愈性创面和近期抗菌药物治疗与创面分泌物病原菌阳性有关。     

烧伤病房患者创面金葡菌分布及耐药性分析

目的分析烧伤病房患者不同创面金葡菌的分布及耐药性,为临床合理选用抗菌药提供依据。方法对2006年1月至2013年12月间中国人民解放军第八五医院烧伤病房患者创面分离出金葡菌,采用K—B纸片扩散法进行药物敏感试验。分析金葡菌的耐药性,并对难愈性创面、非难愈性创面的耐甲氧西林金葡菌（MRSA）与甲氧西林敏感金葡菌（MSSA）的耐药性进行对比分析。结果分离出金葡菌112株,其中难愈性创面有70株MRSA和17株MSSA来自难愈性创面,16株MRSA和9株MSSA来自非难愈性创面。金葡菌对青霉素、红霉素、克林霉素的耐药率较高（分别为94．64％、81．25％和74．11％）,对复方新诺明、呋喃妥因的耐药率较低（分别为16．07％和1．79％）,对万古霉素、利奈唑烷的耐药率为0。MRSA的耐药率高于MSSA。来源于难愈性创面与非难愈性创面的MRSA仅在对利福平的耐药率上有明显差异,而来源于两创面的MSSA的耐药率无明显差异。结论创面金葡菌中MRSA的构成比高,难愈性创面MRSA耐药严重,应积极防控创面MRSA感染和扩散。     

中药抗难愈性创面耐甲氧西林金黄色葡萄球菌研究进展

难愈性创面耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)具有多重耐药性、对消毒剂抗性和形成细菌生物膜等特点。有效针对难愈性创面MRSA的中药应具有抗MRSA和生物膜的能力。本文就近年来的相关研究进展进行了综述。     

Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder

Idiopathic pulmonary fibrosis is a chronic and usually progressive lung disorder of unknown etiology. A growing body of evidence suggests that, in contrast to other interstitial lung diseases, IPF is a distinct entity in which inflammation is a secondary and non-relevant pathogenic partner. Evidence includes the presence of similar mild/moderate inflammation either in early or late disease, and the lack of response to potent anti-inflammatory therapy. Additionally, it is clear from experimental models and some human diseases that it is possible to have fibrosis without inflammation. An evolving hypothesis proposes that IPF may result from epithelial micro-injuries and abnormal wound healing.     

Fibrocytes can be reprogrammed to promote tissue remodeling capacity of dermal fibroblasts

Fibroblasts play a pivotal role in wound healing process participating in both tissue fibrosis and remodeling. However, it remains unclear which factors activate such diversity of fibroblast responses and how this decision-making process is made. Previous reports have demonstrated that wound milieu stimulates the transformation of circulating precursor cells into fibrocytes. These pro-fibrogenic cells promote the collagen production by resident fibroblasts. Conversely, recruited cells with anti-fibrogenic profile that can compete with fibrocytes have not been identified. This report describes a novel transdifferentiation process of fibrocytes induced by changing culture conditions. The reprogrammed fibrocytes markedly increased cell proliferation and MMP-1 expression in dermal fibroblasts. The MMP-1 up-regulation was directly related to the number of fibrocytes that followed this cell transformation. In vitro and in vivo results have confirmed that TGF-β deprivation plays an important role in this novel fibrocyte differentiation pathway. Our findings demonstrate that, changing the fibrocyte commitment, it is possible to exponentially stimulate the tissue remodeling capacity of dermal fibroblasts. These results will open new research approaches to understand the role of cell transdifferentiation and local environment not only in the wound healing process of skin, but also in several other fibrocyte-associated diseases such as lung fibrosis, asthma, liver cirrhosis, chronic pancreatitis, and atherosclerosis.     

Where is biological therapy going?

The substantial progress in our understanding of molecular and cellular biology has allowed us to design biological therapeutics ('biologicals') with defined targets and effector functions. These biologicals have greatly contributed to our current knowledge of pathogenetic mechanisms in autoimmune diseases. However, although some of the biologicals have been extremely successful in treating the symptoms of chronic inflammation, biological therapy has not yet met the expectations of permanently silencing the chronic immune response. In this commentary we discuss current concepts and future directions of biological therapy, and the potential usefulness of biologicals as a treatment of human autoimmune diseases in appropriate critical applications with the use of suitably designed agents.     

Cytokines, growth factors, and plastic surgery.

Numerous inflammatory cytokines and growth factors have been identified and are known to be essential for normal wound healing and host defense, and many have been implicated in disease states treated by plastic surgeons. Cytokines and growth factors are members of a large functional group of polypeptide regulatory molecules secreted by different cell lines. These peptides exert their influence through autocrine and paracrine fashions within sites of injury and repair. Although cytokines and growth factors are crucial in initiating, sustaining, and regulating the postinjury response, these same molecules have been implicated in impaired wound healing, abnormal scarring, and chronic cutaneous diseases. Therapeutic manipulation of inflammatory mediators in normal and impaired wounds has been performed, with mixed clinical results, but evolving strategies such as gene therapy, as well as further characterization of the cellular-mechanism cytokines and growth-factor triggers, will further add to our therapeutic options. This article discusses the current understanding of important cytokines and growth factors involved in the normal injury response and then addresses pathological states associated with an inappropriate expression of these mediators. Finally, a summary of various cytokine and growth factor-directed strategies being used in impaired wound healing states is presented.     

Pneumocystis jirovecii colonization in chronic pulmonary disease

Pneumocystis jirovecii causes pneumonia in immunosuppressed individuals. However, it has been reported the detection of low levels of Pneumocystis DNA in patients without signs and symptoms of pneumonia, which likely represents colonization. Several studies performed in animals models and in humans have demonstrated that Pneumocystis induces a local and a systemic response in the host. Since P jirovecii colonization has been found in patients with chronic pulmonary diseases it has been suggested that P jirovecii may play a role in the physiopathology and progression of those diseases. In this report we revise P. jirovecii colonization in different chronic pulmonary diseases such us, chronic obstructive pulmonary disease, interstitial lung diseases, cystic fibrosis and lung cancer.     

Anti‐aging pharmacology in cutaneous wound healing: effects of metformin,resveratrol, and rapamycin by local application

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate‐activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age‐related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti‐aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR‐based anti‐aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.     

alpha-Lipoic acid modulates extracellular matrix and angiogenesis gene expression in non-healing wounds treated with hyperbaric oxygen therapy

alpha-Lipoic acid (LA) has been found previously to accelerate wound repair in patients affected by chronic wounds who underwent hyperbaric oxygen (HBO) therapy. Because proteinases are important in wound repair, we hypothesized that LA may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Patients undergoing HBO therapy were double-blind randomized into two groups: the LA group and the placebo group. Gene expression profiles for MMPs and for angiogenesis mediators were evaluated in biopsies collected at the first HBO session, at the seventh HBO session, and after 14 days of HBO treatment. ELISA tests were used to validate microarray expression of selected genes. LA supplementation in combination with HBO therapy downregulated the inflammatory cytokines and the growth factors which, in turn, affect MMPs expression. The disruption of the positive autocrine feedback loops that maintain the chronic wound state promotes progression of the healing process.     

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.     

Deconstructing fibrosis research: do pro-fibrotic signals point the way for chronic dermal wound regeneration?

Chronic wounds are characterized by inadequate matrix synthesis, no re-epithelialization, infection and ultimately no wound resolution. In contrast, fibrosis is characterized by overproduction of matrix and excess matrix contraction. As research in the fields of chronic wounds and fibrosis surges forward, important parallels can now be drawn between the dysfunctions in fibrotic diseases and the needs of chronic wounds. These parallels exist at both the macroscopic level and at the molecular level. Thus in finding the individual factors responsible for the progression of fibrotic diseases, we may identify new therapeutic targets for the resolution of chronic wounds. The aim of this review is to discuss how recent advances in fibrosis research have found a home in the treatment of chronic wounds and to highlight the benefits that can be obtained for chronic wound treatments by employing a translational approach to molecules identified in fibrosis research.