adhesion prevention

防粘连
  • 文章类型: Systematic Review
    目的:妇科手术后粘连的形成不仅对患者有不利影响,包括疼痛,阻塞,和不孕症,但也给全球医疗保健系统带来了沉重的经济负担。
    目的:本综述的目的是评估目前所有可用于妇科手术的粘连屏障的粘连预防潜力。
    方法:我们系统地检索了MEDLINE和CENTRAL数据库中关于在妇科手术中使用粘连屏障与腹膜冲洗或不治疗相比的随机对照试验(RCT)。仅包括进行二次手术以评估盆腔/腹腔(但不包括子宫内)粘连的RCT。
    结果:我们纳入了45个随机对照试验,共有4,120名患者在妇科二次手术中检查了10种独特类型的障碍。虽然RCT对氧化再生纤维素(14项试验中有6项显著改善),聚乙二醇有/无其他试剂(4/10),透明质酸和透明质酸盐+羧甲基纤维素(7/10),艾考糊精(1/3),葡聚糖(0/3),含纤维蛋白的药物(1/2),膨体聚四氟乙烯(1/1),N,O-羧甲基壳聚糖(0/1),和改性淀粉(1/1)总体上表现出不一致的发现,膨胀聚四氟乙烯的结果,透明质酸,和改性淀粉在75%的粘附性降低方面产生了最大的改进,0-67%,85%,分别。
    结论:应用Gore-Tex外科膜后,报告了预防粘连的最佳结果,透明质酸,和4DryField®。因为Gore-Tex手术膜是不可吸收的,由于二次手术切除产品,它与新粘连形成的风险更大。与所有其他阻隔剂(85%)相比,4DryField®在粘附分数方面产生了最大的改善。为了更好的可比性,未来的研究应该使用标准化的评分,并更加强调患者报告的结局指标,如疼痛和不孕症。
    OBJECTIVE: The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide.
    OBJECTIVE: The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery.
    METHODS: We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included.
    RESULTS: We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0-67%, and 85%, respectively.
    CONCLUSIONS: Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.
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  • 文章类型: Journal Article
    PP网片是一种广泛用于疝修补术的假体材料。然而,内脏粘连是该手术最严重的并发症之一。因此,通过冻融工艺方法在聚丙烯表面涂覆多孔聚乙烯醇(PVA)水凝胶,开发了一种抗粘连的聚丙烯网。多孔PVA水凝胶涂层的压缩模量首先通过以与PVA的各种质量比添加致孔剂碳酸氢钠(NaHCO3)来调节。不出所料,多孔水凝胶涂层的模量更接近天然腹壁组织。体外试验证明改性PP网片显示出优越的涂层稳固性,优良的血液相容性,和良好的细胞相容性。体内实验表明,模仿天然腹壁模量的PVA4水凝胶涂覆的PP网可以有效防止粘连。基于此,将雷帕霉素(RPM)加载到多孔PVA4水凝胶涂层中,以进一步提高PP网的抗粘附性能。苏木精和伊红(H&E)和马森三色(MT)染色结果证实,所得网状物可以减轻炎症反应并减少胶原在植入区周围的沉积。改性PP网片的仿生力学性能和抗粘连性能使其成为有价值的疝修补术候选材料。本文受版权保护。保留所有权利。
    PP mesh is a widely used prosthetic material in hernia repair. However, visceral adhesion is one of the worst complications of this operation. Hence, an anti-adhesive PP mesh is developed by coating porous polyvinyl alcohol (PVA) hydrogel on PP surface via freezing-thawing process method. The compressive modulus of porous PVA hydrogel coating is first regulated by the addition of porogen sodium bicarbonate (NaHCO3) at various quality ratios with PVA. As expected, the porous hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro tests demonstrate the modified PP mesh show superior coating stability, excellent hemocompatibility, and good cytocompatibility. In vivo experiments illustrate that PP mesh coated by the PVA4 hydrogel that mimicked the modulus of native abdominal wall could prevent adhesion effectively. Based on this, the rapamycin (RPM) is loaded into the porous PVA4 hydrogel coating to further improve anti-adhesive property of PP mesh. The Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining results verified that the resulting mesh could alleviate the inflammation response and reduce the deposition of collagen around the implantation zone. The biomimetic mechanical property and anti-adhesive property of modified PP mesh make it a valuable candidate for application in hernioplasty.
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  • 文章类型: Journal Article
    引言术后粘连存在许多困难,包括肠梗阻和不孕症,由于与粘连相关的问题,他们经常需要重新入院。尽管有这些后果,令人惊讶的是,很少有彻底的全国性调查能解决外科医生对粘合剂的认识。通过评估沙特外科医生术后粘连的知识及其使用抗粘连药物,这项研究旨在缩小这一知识差距。方法本研究是一项横断面观察性研究,针对沙特阿拉伯的外科医生,半结构化在线问卷。问卷通过社交媒体和使用基本随机选择的当面电子邮件分发给参与者。它包括粘连的发病率和患病率,术前知情同意问题,粘连预防观点,和抗粘合化学用途。结果共有111名参与者,41%的人是经验丰富的外科医生,有五年以上的经验。根据调查,大多数外科医生偶尔会使用抗粘连化合物,尤其是在开腹手术中(28%),38%的人在腹腔镜检查时从未使用过它们。研究发现,参与者在告知患者有关粘连并发症的信息方面有所不同:25%的参与者向5%-10%的患者告知了剖腹手术中可能的粘连并发症,而26%的参与者告知10-25%的患者在腹腔镜手术中。与他们的专家同行相比,普通外科医生对粘连和预防的临床意义达成了更多共识。值得注意的是,四分之三的参与者不清楚何时使用抗粘连化合物.结论在承认术后粘连的临床意义并认识到预防的潜力的同时,大多数接受调查的外科医生在知情同意中没有将粘连作为术后并发症.该研究强调了对抗粘合剂功效的信念,但揭示了其使用的具体适应症普遍缺乏清晰度。建议包括在手术培训期间实施教育课程,以提高对粘连作为术后主要并发症的认识,并鼓励适当利用可用的屏障和药物抗粘连产品。
    Introduction Post-operative adhesions present a number of difficulties, including intestinal obstruction and infertility, and they frequently require readmission due to adhesion-related problems. Notwithstanding these ramifications, there are surprisingly few thorough national surveys that address surgeons\' awareness of adhesives. By assessing Saudi surgeons\' knowledge of post-operative adhesions and their use of anti-adhesive medications, this study aims to close this knowledge gap. Methods This study is a cross-sectional observational research study aimed at Saudi Arabian surgeons utilizing a self-administered, semi-structured online questionnaire. The questionnaire was distributed to participants via social media and in-person email using basic random selection. It included adhesion morbidity and prevalence, pre-operative informed consent issues, adhesion preventive viewpoints, and anti-adhesive chemical use. Results There were 111 participants in total, of 41% were experienced surgeons with more than five years of experience. According to the survey, the majority of surgeons occasionally employed anti-adhesive compounds, especially during laparotomies (28%), and 38% never used them during laparoscopies. The study found that participants varied in what they informed patients regarding adhesion complications: 25% of participants informed 5%-10% of the patients about the possible adhesion complications in laparotomy procedures, whereas 26% of participants informed 10-25% of the patients in laparoscopic procedures. Compared with their specialist peers, general surgeons agreed more on the clinical significance of adhesions and prevention. Notably, three-quarters of participants were unclear about when to use anti-adhesive compounds. Conclusion While acknowledging the clinical significance of post-operative adhesions and recognizing the potential for prevention, most surveyed surgeons did not include adhesions as a post-operative complication in informed consent. The study underscores a belief in the efficacy of anti-adhesives yet reveals a widespread lack of clarity regarding specific indications for their use. Recommendations include implementing educational sessions during surgical training to heighten awareness of adhesions as a major post-operative complication and to encourage the appropriate utilization of available barriers and pharmacological anti-adhesive products.
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  • 文章类型: Journal Article
    开发用于预防术后粘连的抗粘连水凝胶是一个持续的挑战,特别是在实现优异的防污性能和有效的原位组织保留之间的平衡。在这项研究中,我们提出了一种独特的方法,设计了具有仿生微结构的单组分Janus两性离子水凝胶贴片。Janus贴剂是通过磺基甜菜碱甲基丙烯酸酯与N,N'-亚甲基双(2-丙烯酰胺)作为交联剂。当Janus水凝胶贴片应用于受创伤的组织时,通过在一侧互连凹槽分开的六边形小平面的结合为其提供了持久且可靠的原位保留能力。相对的平坦表面对细菌表现出突出的抵抗力,蛋白质,和细胞粘附,由于两性离子聚合物的超亲水性和优异的防污特性。这种双重功能使Janus水凝胶贴片能够减轻创伤和周围组织之间的粘连。六边形和凹槽仿生微结构有利于快速排水,促进与组织的快速接触,以增加粘附强度,而独立的六边形微面增强剥离能量。在体内环境中,具有表面微结构的Janus两性离子水凝胶贴片与盲肠表面形成相互嵌入的结构,最大限度地减少打滑和脱离的可能性。值得注意的是,涉及腹壁盲肠损伤的体内实验表明,与商业对照相比,Janus两性离子水凝胶贴片具有优异的抗粘连效果。因此,Janus水凝胶贴片,以其仿生微结构表面而著称,在生物医学领域为避免术后粘连提供了巨大的潜力。
    The development of anti-adhesion hydrogels for preventing postoperative adhesions is an ongoing challenge, particularly in achieving a balance between exceptional antifouling properties and effective in situ tissue retention. In this study, we propose a unique approach with the design of a single-component Janus zwitterionic hydrogel patch featuring a bionic microstructure. The Janus patches were prepared through free radical polymerization of sulfobetaine methacrylate with N, N\'-methylenebis(2-propenamide) as the cross-linker. The incorporation of hexagonal facets separated by interconnecting grooves on one side imparts durable and reliable in situ retention capabilities to the Janus hydrogel patch when it is applied to traumatized tissues. The opposing flat surface exhibits outstanding resistance to bacteria, proteins, and cell adhesion, due to the superhydrophilicity and excellent antifouling characteristics of zwitterionic polymers. This dual functionality empowers the Janus hydrogel patch to mitigate adhesions between traumatized and surrounding tissues. The hexagonal and groove bionic microstructures facilitate rapid drainage, promoting swift contact with the tissue for increased adhesion strength, while independent hexagonal microfacets enhance the peeling energy. In an in vivo setting, Janus zwitterionic hydrogel patches with surface microstructures form mutually embedded structures with the cecum surface, minimizing the likelihood of slippage and detachment. Remarkably, in vivo experiments involving abdominal wall cecum injuries illustrate the Janus zwitterionic hydrogel patch\'s superior anti-adhesion effectiveness compared to commercial controls. Thus, the Janus hydrogel patch, distinguished by its bionic microstructure surface, presents substantial potential in the biomedical field for averting postoperative adhesions.
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  • 文章类型: Journal Article
    这项研究的目的是研究D-柠檬烯对降低大鼠术后粘连的影响,并了解相关机制。通过创建不同的切口并切除腹膜的1×1cm切片来诱导腹膜粘连。实验组包括假手术组,对照组在没有任何治疗的情况下诱导腹膜粘连,和两个治疗组,其中动物在诱导腹膜粘连后接受剂量为25和50mg/kg的D-柠檬烯。粘连的宏观检查显示,与对照组相比,两个治疗组的粘连带减少。TGF-β1、TNF-α、在第14天,VEGF显示对照组中上述标志物的免疫阳性细胞水平显着增加,而柠檬烯在两种剂量中的施用显着降低了TGF-β1,TNF-α的水平,VEGF(P<0.05)。对照组诱导腹膜粘连显著增加TGF-β1、TNF-α、在蛋白质印迹评估中第3天和第14天和VEGF,而柠檬烯治疗可显著降低第14天的TNF-α水平(P<0.05)。此外,两个治疗组中的VEGF水平在第3天和第14天显著降低。在对照组中,MDA和NO水平显着增加,GPX水平显着下降,观察到CAT(P<0.05)。柠檬烯50组于第14天显著降低MDA水平,升高GPx和CAT水平(P<0.05)。总之,D-柠檬烯减少粘附带,炎性细胞因子,血管生成,和氧化应激。
    The aim of this research was to investigate the effects of D-limonene on decreasing post-operative adhesion in rats and to understand the mechanisms involved. Peritoneal adhesions were induced by creating different incisions and excising a 1 × 1 cm section of the peritoneum. The experimental groups included a sham group, a control group in which peritoneal adhesions were induced without any treatment, and two treatment groups in which animals received D-limonene with dosages of 25 and 50 mg/kg after inducing peritoneal adhesions. Macroscopic examination of adhesions showed that both treatment groups had reduced adhesion bands in comparison to the control group. Immunohistochemical assessment of TGF-β1, TNF-α, and VEGF on day 14 revealed a significant increment in the level of immunopositive cells for the mentioned markers in the control group, whereas administration of limonene in both doses significantly reduced levels of TGF-β1, TNF-α, and VEGF (P < 0.05). Induction of peritoneal adhesions in the control group significantly increased TGF-β1, TNF-α, and VEGF on days 3 and 14 in western blot evaluation, while treatment with limonene significantly reduced TNF-α level on day 14 (P < 0.05). Moreover, VEGF levels in both treatment groups significantly reduced on days 3 and 14. In the control group, a significant increment in the levels of MDA and NO and a notable decline in the levels of GPX, CAT was observed (P < 0.05). Limonene 50 group significantly reduced MDA level and increased GPx and CAT levels on day 14 (P < 0.05). In summary, D-limonene reduced adhesion bands, inflammatory cytokines, angiogenesis, and oxidative stress.
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  • 文章类型: Journal Article
    术后粘连是腹部手术中值得注意的临床并发症,因为现有的物理屏障不能令人满意且预防其发生效率低下。在这项工作中,提出了一种精细的纳米颗粒微凝胶系统(nMGel)用于预防术后粘连。nMGel是通过使用改进的乳化-化学交联方法将载有二氧化锰(MnO2)纳米颗粒的明胶微球与聚多巴胺交联而容易形成的,产生纳米微米球形水凝胶。干燥后,具有喷雾性的粉状nMGel可以完美地覆盖不规则的伤口,即使在潮湿的环境中也能保持强大的组织粘附性。此外,NMGel具有突出的抗氧化和自由基清除活性,在氧化微环境中保护细胞活力并保持细胞生物学功能。此外,nMGel显示出如在小鼠尾部截肢模型和肝创伤模型中所证明的优越的止血性质。重要的是,nMGel可以方便地在小鼠盲肠缺损模型中施用,以通过减少炎症来防止损伤的盲肠和腹膜之间的粘连。氧化应激,胶原蛋白合成,和血管生成。因此,生物活性nMGel为改善术后粘连提供了一种实用有效的方法.
    Postoperative adhesion is a noteworthy clinical complication in abdominal surgery due to the existing physical barriers are unsatisfactory and inefficient in preventing its occurrence. In this work, an elaborate nanoparticle-in-microgel system (nMGel) is presented for postoperative adhesion prevention. nMGel is facilely formed by crosslinking manganese dioxide (MnO2) nanoparticles-loaded gelatin microspheres with polydopamine using a modified emulsification-chemical crosslinking method, generating a nano-micron spherical hydrogel. After drying, powdery nMGel with sprayability can perfectly cover irregular wounds and maintains robust tissue adhesiveness even in a wet environment. Additionally, nMGel possesses prominent antioxidant and free radical scavenging activity, which protects cell viability and preserves cell biological functions in an oxidative microenvironment. Furthermore, nMGel displays superior hemostatic property as demonstrated in mouse tail amputation models and liver trauma models. Importantly, nMGel can be conveniently administrated in a mouse cecal defect model to prevent adhesion between the injured cecum and the peritoneum by reducing inflammation, oxidative stress, collagen synthesis, and angiogenesis. Thus, the bioactive nMGel offers a practical and efficient approach for ameliorating postsurgical adhesion.
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  • 文章类型: Journal Article
    术后粘连是外科手术的常见并发症,可导致术后疼痛,肠梗阻,不孕症,以及未来手术的并发症。已经开发了几种防止粘连形成的试剂,如障碍,抗炎药和纤维蛋白溶解药。美国食品和药物管理局(FDA)已批准使用物理屏障剂,但它们与相互矛盾的临床研究和抗粘连屏障临床应用的争议有关。在这次审查中,我们总结了人体腹膜的解剖结构,粘连形成的病理生理学,目前的预防措施,以及目前预防粘连的研究进展。最近发现,从损伤的间皮细胞开始并掺入巨噬细胞反应的早期细胞事件与粘附形成有关。这可以为开发未来的防粘连方法提供关键部分。目前使用物理屏障来分离组织,如Seprafilm®,由透明质酸和羧甲基纤维素组成,只能降低在最后阶段形成粘连的风险。其他用于预防粘连的抗炎或纤维蛋白溶解药物仅在当前研究模型的背景下进行了研究。这是由于缺乏体外模型系统以及对体内模型进行深入研究以评估抗粘连剂的有效性。此外,我们探索新兴的疗法,如基因治疗和基于干细胞的方法,这可能为防止粘连形成提供新的策略。总之,抗粘连剂是减少手术患者粘连相关并发症负担的一种有希望的方法.需要进一步的研究来优化它们的使用,并为这个具有挑战性的临床问题开发新的疗法。
    Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti-inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti-adhesion barriers. In this review, we summarize the human anatomy of the peritoneum, the pathophysiology of adhesion formation, the current prevention agents, as well as the current research progress on adhesion prevention. The early cellular events starting with injured mesothelial cells and incorporating macrophage response have recently been found to be associated with adhesion formation. This may provide the key component for developing future adhesion prevention methods. The current use of physical barriers to separate tissues, such as Seprafilm®, composed of hyaluronic acid and carboxymethylcellulose, can only reduce the risk of adhesion formation at the end stage. Other anti-inflammatory or fibrinolytic agents for preventing adhesions have only been studied within the context of current research models, which is limited by the lack of in-vitro model systems as well as in-depth study of in-vivo models to evaluate the efficiency of anti-adhesion agents. In addition, we explore emerging therapies, such as gene therapy and stem cell-based approaches, that may offer new strategies for preventing adhesion formation. In conclusion, anti-adhesion agents represent a promising approach for reducing the burden of adhesion-related complications in surgical patients. Further research is needed to optimize their use and develop new therapies for this challenging clinical problem.
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  • 文章类型: Randomized Controlled Trial
    目的:为了检验以下假设:腹膜内滴注1-丙氨酰-1-谷氨酰胺(AG)的单次推注剂量会降低发病率,子宫肌瘤切除术后粘连的程度和/或严重程度,并建立AG在人类中的初步安全性和耐受性。
    方法:阶段1,2随机,双盲,安慰剂对照研究(DBRCT)。
    方法:三级护理妇科手术中心。
    方法:38名妇女在6-8周后通过腹腔镜检查(N=38;AG-19vs安慰剂-19)或剖腹手术(N=10;AG-5vs安慰剂-5)进行了子宫肌瘤切除术。腹腔镜臂中的32例患者完成了SLL。
    方法:在腹腔镜端口缝合闭合之前立即腹膜内施用Bolus剂量的AG或生理盐水溶液对照(0.9%NaCl)。基于lg/kg体重的给药方案,平均剂量为170mLAG或对照。
    方法:获得所有手术的数字录音。主要终点是发病率的降低,通过意向治疗(ITT)方法分析术后粘连的严重程度和程度。三个独立的,盲审核员评估了所有手术录像,以评估是否存在粘连.事后分析评估腹膜腔中是否存在粘连。次要终点评估AG的安全性和耐受性。
    结果:服用AG降低了发病率,术后粘连的严重程度和/或程度(p=0.046)。AG组中粘连的存在低于对照组(p=0.041)。AG组中15个中的15个(100%)实现粘附性改善,而安慰剂组中17个中的5个(29.6%)实现粘附性改善。未报告严重不良事件。没有观察到安全参数的差异。
    结论:腹膜内l-丙氨酰-l-谷氨酰胺可减少腹腔镜子宫肌瘤切除术后所有患者的粘连形成。在93%的患者中,所有腹部部位都完全没有粘连。结果证实了AG对粘连发生的细胞机制的已知作用,为新的粘连预防研究和治疗奠定了基础。
    OBJECTIVE: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans.
    METHODS: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT).
    METHODS: Tertiary care gynecology surgical centre.
    METHODS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL.
    METHODS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight.
    METHODS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG.
    RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed.
    CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG\'s known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.
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  • 文章类型: Journal Article
    术后腹膜粘连是术后常见的并发症,发病率高。除了改善外科手术,药物治疗和物理屏障是预防术后腹膜粘连的两种主要方法。单一的防粘连方法往往不能获得满意的疗效,屏障疗法和抗粘连药物的结合引起了更多的关注。在这项研究中,我们首先证明补体激活异常与腹膜损伤和炎症反应相关.相应地,阻断C5a-C5aR轴反应可有效减轻炎症反应。因此,我们创造性地开发了一种针对腹膜粘连的木葡聚糖衍生物(mXG)水凝胶和静脉内抗C5a受体抗体(抗C5aRab)的综合治疗,然后使用小鼠侧壁缺损-盲肠磨损模型系统地评估治疗效果。体外和体内实验表明,mXG水凝胶具有良好的生物相容性和降解性,可以作为一种安全的抗粘连屏障。结果表明,抗C5aRab治疗可通过减少中性粒细胞浸润和磷酸化Smad2的表达来显著抑制腹膜粘连。一起来看,与抗C5aRab整合的mXG水凝胶显示出优异的抗粘连性能,在预防腹膜粘连方面具有良好的临床应用前景。意义声明:术后腹膜粘连是术后急需解决的问题。以前,开发了一种可生物降解和热可逆的木葡聚糖衍生物(mXG)水凝胶,可有效防止术后腹膜粘连,但仍可观察到明显的炎症反应和增殖。此外,补体激活异常与多种炎症性疾病有关。我们证明了异常补体激活与腹膜粘连有关。在这项工作中,整合mXG水凝胶和静脉内抗C5a受体抗体(抗C5aRab)以解决腹膜粘连。抗C5aRab降低了炎症反应。此外,mXG水凝胶易于使用,可有效隔离局部损伤部位的伤口表面。总的来说,这种综合治疗显著提高了抗粘连效果。
    Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.
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  • 文章类型: Journal Article
    每年对数百万人进行肠道部位的吻合手术。然而,几个持续的并发症,如吻合口漏,异常粘连,吻合口狭窄,手术后观察到了。为了促进吻合口愈合并克服上述挑战,吻合部位的再上皮化是至关重要的。在这项研究中,制备了一种促进上皮化的大分子前药Ala-Gln-PPDO,并通过静电纺丝加工成纤维膜。Ala-Gln和庆大霉素从静电纺丝膜中持续释放,并降解这些膜,以促进大鼠肠上皮细胞的增殖并抑制金黄色葡萄球菌和大肠杆菌的增殖。本研究已在大鼠肠吻合模型中评估了Ala-Gln-PPDO膜的综合修复作用。Ala-Gln-PPDO膜的应用,尤其是庆大霉素掺入的Ala-Gln-PPDO,可以防止受伤的肠道和周围肠道组织之间的粘连。此外,它们不会对吻合口的愈合强度产生负面影响,并且可以促进吻合部位的再上皮化。此外,庆大霉素掺入的Ala-Gln-PPDO膜可以缓解吻合口狭窄。庆大霉素掺入Ala-Gln-PPDO电纺膜是一种很有前途的,促进胃肠吻合术后愈合的综合性可植入材料由于其涉及促进再上皮化的作用,防止粘连,并缓解吻合口狭窄。
    Anastomosis surgery at the intestinal site is performed on millions of individuals every year. However, several persistent complications, such as anastomotic leakage, abnormal adhesion, and anastomotic stenosis, have been observed after the surgery. For promoting anastomotic healing and to overcome the challenges mentioned above, re-epithelialization at anastomotic sites is crucial. In this study, an epithelialization-promoting macromolecular prodrug Ala-Gln-PPDO was prepared and processed into fibrous membranes by electrospinning. Ala-Gln and gentamicin were sustainably released from the electrospun membranes with degradation of these membranes to promote the proliferation of rat intestinal epithelial cells and suppress the proliferation of Staphylococcus aureus and Escherichia coli. The comprehensive repair effects of Ala-Gln-PPDO membranes have been evaluated in rat models of intestinal anastomosis in this study. Application of Ala-Gln-PPDO membranes, especially the gentamicin-incorporated Ala-Gln-PPDO ones, could prevent adhesion between the injured intestine and surrounding intestinal tissues. In addition, they did not affect the healing strength of anastomotic stoma negatively and could promote re-epithelialization at the anastomotic sites. Furthermore, the gentamicin-incorporated Ala-Gln-PPDO membranes could relieve stenosis at anastomotic sites. The gentamicin-incorporated Ala-Gln-PPDO electrospun membrane is a promising, comprehensive implantable material for promoting healing after gastrointestinal anastomosis owing to its effects involving the promotion of re-epithelialization, prevention of adhesion, and relieving of anastomotic stenosis.
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