Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-t...Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.展开更多
Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so...Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so far,no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention.Chinese medicine(CM)has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine.Therefore,this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments,including their pharmacological effects,therapeutic mechanisms and advantages in PA prevention.We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.展开更多
More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in applicatio...More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.展开更多
BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion ar...BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.展开更多
Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity...Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity in doses too close to the lowest therapeutic dose, the aim in the present study was to investigate the possible antiadhesive effect of another four cationic polypeptides. Materials/Methods: 125 mice were studied with a standardized and reproducible adhesion model and given epsilon poly-L-lysine, lactoferrin, lysozyme and polyarginine respectively in a combination with poly-L-glutamate. Epsilon poly-L-lysine was also tested in different concentrations and as single treatment. Results: All four cationic polypeptides above showed a significantly better anti-adhesive effect than the controls receiving saline (p<0.05). Epsilon poly-L-lysine had the best antiadhesive effect of the new substances tested in the experiment. Single treatment with the epsilon poly-L-lysine showed toxic side effects. Discussion: We have shown that epsilon poly-L-lysine, polyarginine, lysozyme and lactoferrin, in descending order, all can reduce postoperative intraabdominal adhesions in mice when combined with poly-L-glutamate. There were side effects of epsilon poly-L-lysine resembling those of α-poly-L-lysine, although less toxic. The antiadhesive effect of epsilon poly-L-lysine did not reach the level of α-poly-L-lysine. Further studies will concentrate on additional investigation, trying to modify the α-poly-L-lysine to lower its toxicity. The less toxic epsilon poly-L-lysine also needs further attention in our research of antiadhesive bioactive polypeptides.展开更多
AIM To assess the effectiveness of Daikenchuto for patients with postoperative adhesive small bowel obstruction(ASBO).METHODS A systematic search of Pub Med(MEDLINE),CINAHL,the Cochrane Library and Ichushi Web was con...AIM To assess the effectiveness of Daikenchuto for patients with postoperative adhesive small bowel obstruction(ASBO).METHODS A systematic search of Pub Med(MEDLINE),CINAHL,the Cochrane Library and Ichushi Web was conducted,and the reference lists of review articles were handsearched.The outcomes of interest were the incidence rate of surgery,the length of hospital days and mortality.The quality of the included studies,publication bias and between-study heterogeneity were also assessed.RESULTS Three randomized controlled trials(RCTs)and three retrospective cohort studies were selected for analysis.In the three RCTs,Daikenchuto significantly reduced the incidence of surgery(p OR=0.13;95%CI:0.03-0.50).Similarly,Daikenchuto significantly reduced the incidence of surgery(p OR=0.53;95%CI:0.32-0.87)in the three cohort studies.The length of hospital stay and mortality were not measured or described consistently.CONCLUSION The present meta-analysis demonstrates that administering Daikenchuto is associated with a lower incidence of surgery for patients with postoperative ASBO in the Japanese population.In order to better generalize these results,additional studies will be needed.展开更多
Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combinat...Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination.To this end,we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer.The inner adhesive layer tightly and instantly adheres to the wound sites via-NHS chemistry;the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure;and the interlayer enhances the bulk resilience of the patch under excessive deformation.This complementary trilayer patch(TLP)possesses a unique combination of instant wet adhesion,high mechanical strength,and biological inertness.Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion.The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.展开更多
Postsurgical adhesion is a common clinic disease induced by surgical trauma,accompanying serious subsequent complications.Current non-surgical approaches of drugs treatment and biomaterial barrier administration only ...Postsurgical adhesion is a common clinic disease induced by surgical trauma,accompanying serious subsequent complications.Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn’t effectively promote peritoneum repair.Herein,inspired by bottlebrush,a novel self-fused,antifouling,and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid(HA-GMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)monomer without any chemical crosslinkers,termed as H-HPMA hydrogel.The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time.Intriguingly,the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability.The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis in vivo.The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days.Furthermore,an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition(MMT)process dominated by the TGF-β-Smad2/3 signal pathway.Thus,we developed a simple,effective,and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis,offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.展开更多
基金financial support from the National Natural Science Foundation of China(Nos.32171345,T2288101,U20A20390,and 11827803)Fok Ying Tung Education Foundation(No.141039)+1 种基金International Joint Research Center of Aerospace Biotechnology and Medical Engineering,Ministry of Science and Technology of China,the 111 Project(No.B13003)the Academic Excellence Foundation of BUAA for PhD Students.
文摘Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.
基金Supported by the National Natural Science Foundation of China(Nos.82174394,81673982,81704084)the Science and Technology Development Fund,Macao SAR(No.0121/2022/A3)+5 种基金the Faculty Research Grants of Macao University of Science and Technology(No.FRG-22-110-FC)the Natural Science Foundation of JiangsuProvince(No.BK20201401)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX21_1667)Chinese Medicine Technology Development Project of Jiangsu Province(No.QN202002)the Natural Science Foundation of Nanjing University of Chinese Medicine(No.NZY81704084)the Open Projects of the Discipline of Chinese Medicine of Nanjing University Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions(No.ZYX03KF63)。
文摘Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so far,no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention.Chinese medicine(CM)has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine.Therefore,this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments,including their pharmacological effects,therapeutic mechanisms and advantages in PA prevention.We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
基金funding from the National Institutes of Health(1R01EB023052,1R01HL140618,1R01HL137193,1R01GM126831)the financial support from the Canadian Institutes of Health Research(CIHR)through a postdoctoral fellowshipthe startup fund from the Pennsylvania State University。
文摘More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.
基金Supported by the National Natural Science Foundation of China,No.81704084,No.81603529,and No.81673982the Science and Technology Projects of Jiangsu Provincial Bureau of Traditional Chinese Medicine,No.YB2017002 and No.YB2015002+4 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions,No.16KJB360002the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_1541the Qing Lan Projectthe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine(ZYX03KF63)Jiangsu Government Scholarship for Overseas Studies and China Scholarship Council
文摘BACKGROUND Postoperative peritoneal adhesion(PPA),characterized by abdominal pain,female infertility,and even bowel obstruction after surgery,has always been a major concern.The occurrence and formation of adhesion are from complex biological processes.However,the molecular mechanisms underlying the basis of microarray data profile,followed by peritoneal adhesion formation,are largely unknown.AIM To reveal the underlying pathogenesis of PPA at the molecular level.METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis.We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods.We performed quantitative PCR and western blotting in vivo to validate the results preliminarily.RESULTS In total,446 expressed genes were altered in peritoneal adhesion.We found that several hub genes(e.g.,tumor necrosis factor,interleukin 1 beta,interleukin 6,CX-C motif chemokine ligand 1,C-X-C motif chemokine ligand 2)were marked as significant biomarkers.Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway.According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies,TLR4,myeloid differentiation primary response protein 88(MyD88),and nuclear factor kappa B(NF-κB)played essential roles in Toll-like signaling transduction.Here,we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion.The results of the microarray analysis were verified by the animal experiments.These findings may extend our understanding of the molecular mechanisms of PPA.CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA.Future studies are required to validate our findings.
文摘Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity in doses too close to the lowest therapeutic dose, the aim in the present study was to investigate the possible antiadhesive effect of another four cationic polypeptides. Materials/Methods: 125 mice were studied with a standardized and reproducible adhesion model and given epsilon poly-L-lysine, lactoferrin, lysozyme and polyarginine respectively in a combination with poly-L-glutamate. Epsilon poly-L-lysine was also tested in different concentrations and as single treatment. Results: All four cationic polypeptides above showed a significantly better anti-adhesive effect than the controls receiving saline (p<0.05). Epsilon poly-L-lysine had the best antiadhesive effect of the new substances tested in the experiment. Single treatment with the epsilon poly-L-lysine showed toxic side effects. Discussion: We have shown that epsilon poly-L-lysine, polyarginine, lysozyme and lactoferrin, in descending order, all can reduce postoperative intraabdominal adhesions in mice when combined with poly-L-glutamate. There were side effects of epsilon poly-L-lysine resembling those of α-poly-L-lysine, although less toxic. The antiadhesive effect of epsilon poly-L-lysine did not reach the level of α-poly-L-lysine. Further studies will concentrate on additional investigation, trying to modify the α-poly-L-lysine to lower its toxicity. The less toxic epsilon poly-L-lysine also needs further attention in our research of antiadhesive bioactive polypeptides.
文摘AIM To assess the effectiveness of Daikenchuto for patients with postoperative adhesive small bowel obstruction(ASBO).METHODS A systematic search of Pub Med(MEDLINE),CINAHL,the Cochrane Library and Ichushi Web was conducted,and the reference lists of review articles were handsearched.The outcomes of interest were the incidence rate of surgery,the length of hospital days and mortality.The quality of the included studies,publication bias and between-study heterogeneity were also assessed.RESULTS Three randomized controlled trials(RCTs)and three retrospective cohort studies were selected for analysis.In the three RCTs,Daikenchuto significantly reduced the incidence of surgery(p OR=0.13;95%CI:0.03-0.50).Similarly,Daikenchuto significantly reduced the incidence of surgery(p OR=0.53;95%CI:0.32-0.87)in the three cohort studies.The length of hospital stay and mortality were not measured or described consistently.CONCLUSION The present meta-analysis demonstrates that administering Daikenchuto is associated with a lower incidence of surgery for patients with postoperative ASBO in the Japanese population.In order to better generalize these results,additional studies will be needed.
基金financially supported by the National Key Research and Development Program of China(2021YFB3800800,2018YFA0703000)the Science and Technology Program of Guangdong Province(2019B010941002)+3 种基金Science and Technology Program of Guangzhou(202206040001)the National Natural Science Foundation of China(32022041,U22A20157)the Key Research and Development Program of Guangzhou(20200702000,22020B1515120075)the Guangdong Basic and Applied Basic Research Foundation Outstanding Youth Project(2021B1515020064).
文摘Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination.To this end,we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer.The inner adhesive layer tightly and instantly adheres to the wound sites via-NHS chemistry;the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure;and the interlayer enhances the bulk resilience of the patch under excessive deformation.This complementary trilayer patch(TLP)possesses a unique combination of instant wet adhesion,high mechanical strength,and biological inertness.Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion.The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.
基金supported by the National Natural Science Foundation of China(Grant Nos.81773686,32171336)the Natural Science Foundation of Shaanxi Province(Grant Nos.2021 SF-108,2021 SF-308)。
文摘Postsurgical adhesion is a common clinic disease induced by surgical trauma,accompanying serious subsequent complications.Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn’t effectively promote peritoneum repair.Herein,inspired by bottlebrush,a novel self-fused,antifouling,and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid(HA-GMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)monomer without any chemical crosslinkers,termed as H-HPMA hydrogel.The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time.Intriguingly,the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability.The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis in vivo.The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days.Furthermore,an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition(MMT)process dominated by the TGF-β-Smad2/3 signal pathway.Thus,we developed a simple,effective,and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis,offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.
