Background:Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion.These pathological behaviours may be related to the heterogeneity of keloid fibroblasts(KFs...Background:Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion.These pathological behaviours may be related to the heterogeneity of keloid fibroblasts(KFs);however,because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism.Our previous studies revealed that the expansion of CD26+KFs was responsible for increased keloid proliferation and invasion capabilities;the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation.The aim of this studywas to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities,and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target.Methods:Flow cytometry was performed to isolate CD26+/CD26−fibroblasts from KFs and normal fibroblasts.To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor(IGF-1R),lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection.Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2-deoxyuridine(EdU)incorporation assay.Scratching assay and transwell assay were used to assess cell migration and invasion abilities.To further quantify the regulatory role of CD26 expression in the relevant signalling pathway,RT-qPCR,western blot,ELISA,PI3K activity assay and immunofluorescence were used.Results:Aberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs.Furthermore,the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion.The PI3K/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein.Conclusions:CD26 can be the effective biomarker for KFs,and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway.This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.展开更多
Background:Reconstruction of upper and lower lip subunits is a complicated and elusive challenge.For patients affected by defects involving upper and lower lip subunits,a technique able to reconstruct both aesthetic u...Background:Reconstruction of upper and lower lip subunits is a complicated and elusive challenge.For patients affected by defects involving upper and lower lip subunits,a technique able to reconstruct both aesthetic units with matched colour,sufficient contours and similar texture would be ideal.In this study,we present our experience with upper and lower lip reconstruction using the pre-expanded bipedicled visor flap.Methods:From January 2014 to January 2017,12 male patients presenting with defects of the upper and lower lip subunits were treated using this surgical technique.After a period of expansion of the scalp flap of over 6 months,the bipedicled visor flap was raised from both the parietal regions and rotated to resurface the defect.Delay and section of the pedicle were then performed.Results:Twelve male patients with postburn scars aged 22 to 48 years(mean:34 years)were successfully treated with no major complications.The donor site was closed primarily in all cases.Subsequent flap debulking and minor revisions were performed under local anaesthesia between 6 and 12 months postoperatively.Conclusions:The pre-expanded bipedicled visor flap provides an effective and reliable option for upper and lower lip reconstruction with excellent colour and texture.It is feasible to achieve these results simultaneously from a single donor site by using a pre-expanded bipedicled visor flap.展开更多
Background:An ideal tension-relieving suture should be efficient for>3 months to retrieve normal tensile strength.Most preexisting suturing techniques provided tension elimination followed by relapse and scar proli...Background:An ideal tension-relieving suture should be efficient for>3 months to retrieve normal tensile strength.Most preexisting suturing techniques provided tension elimination followed by relapse and scar proliferation due to absorption and cut-through of the sutures.This study introduces a simple but effective suture technique developed by a senior author(ZYX)to solve this problem.Methods:A total of 120 patients with pathological scar(PS)had intervention treatment with the proposed suturing strategy at three centers from January 2018 to January 2021.A slowly absorbable 2-0 barbed suturewas used for subcutaneous tension relieving with a set-back from the wound edge and a horizontal interval between proposed inserting points of 1 cm.The Patient and Observer Scar Assessment Scale(POSAS),scar width,perfusion and eversion of the wound edge were evaluated at 3-,6-and 12-month follow-up.The time needed to place the tension-relieving suture was recorded and relapse was monitored for 18 months postoperatively.Results:In total,76 trunks,32 extremities and 12 cervical PS were included,with an average subcutaneous tension-relieving suture time of 5 min.The Patient and Observer Scar Assessment Scale(POSAS)score decreased from 84.70±7.06 preoperatively to 28.83±3.09,26.14±1.92 and 24.71±2.00 at 3,6 and 12 months postoperatively,respectively(p<0.0001).The scar widths were 0.17±0.08,0.25±0.09 and 0.33±0.10 cm,respectively,with perfusion significantly decreased from 213.64±14.97 to 112.23±8.18 at 6 months(p<0.0001).The wound edge flattened out during the first 3 months in most cases with only two scar relapses.Conclusions:Zhang’s suture technique provides a rapid and long-lasting tension-relieving effect with ideal scar appearances and lower relapse rates in the surgical management of PS.展开更多
Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessiv...Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior.Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation.This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation.Methods:Here,augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts(HFs)and HS tissues,and the suppression of glycolysis also attenuated fibroblast activation.We also introduced IR780,a heptamethine cyanine dye,to regulate glycolysis for the control of HS formation.Results:In vitro,cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs.In vivo,the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation.Furthermore,IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies,and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts.Conclusions:This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.展开更多
Background:Several surgeons have described studies of free-tissue transfers using veins instead of arteries.These innovative microsurgical techniques can offer several advantages,such as an easier dissection during fl...Background:Several surgeons have described studies of free-tissue transfers using veins instead of arteries.These innovative microsurgical techniques can offer several advantages,such as an easier dissection during flap harvesting,and represent an alternative during an accidental surgical mistake or development of new surgical procedures.The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer(VLNT)only based on venous blood flow in a mouse model,evaluate their blood flow microcirculation through indocyanine green(ICG)angiography and investigate the lymphatic drainage function and the lymph nodes’structures.Methods:Five types of venous lymph node flaps(LNF)were created and investigated:Types IA,IB,IC,IIA and IIB were developed by ICG intraoperatively(with videos in the article).Seven weeks later,by applying methylene blue,the recanalization of the lymphatic vessels between the LNF and the recipient site was detected.Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis.Results:All of the venous LNFs developed except Type IC.Seven weeks later,methylene blue flowed into Types IA,IB,IIA and IIB from recipient sites.When comparing with arteriovenous lymph node,the medullary sinus was diffusely distributed in venous lymph nodes.The proportion of cells was significantly reduced(p<0.05).The artery diameters were significantly smaller(p<0.05).The veins diameters and lymphatic vessels output in Types IA,IB,IIA and IIB were more dilated(p<0.05).Conclusions:This research demonstrated that Type IA,IB,IIA and IIB venous LNFs can retrogradely receive venous blood supply;they can survive,produce a lymphatic recanalization and integrate with the surrounding tissue,despite lymph node structural changes.Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.展开更多
基金supported by the National Natural Science Foundation of China(81772098,81801917,81801918)the Outstanding Professional and Technical Leader Program of the Shanghai Municipal Science and Technology Commission(18XD1423700)+3 种基金the Clinical Multi-Disciplinary Team Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(2017-1-007)the Clinical Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYLJ027)the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152227)the project of Science and Technology Commission of Shanghai Municipality(17411952800,18441904500).
文摘Background:Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion.These pathological behaviours may be related to the heterogeneity of keloid fibroblasts(KFs);however,because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism.Our previous studies revealed that the expansion of CD26+KFs was responsible for increased keloid proliferation and invasion capabilities;the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation.The aim of this studywas to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities,and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target.Methods:Flow cytometry was performed to isolate CD26+/CD26−fibroblasts from KFs and normal fibroblasts.To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor(IGF-1R),lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection.Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2-deoxyuridine(EdU)incorporation assay.Scratching assay and transwell assay were used to assess cell migration and invasion abilities.To further quantify the regulatory role of CD26 expression in the relevant signalling pathway,RT-qPCR,western blot,ELISA,PI3K activity assay and immunofluorescence were used.Results:Aberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs.Furthermore,the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion.The PI3K/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein.Conclusions:CD26 can be the effective biomarker for KFs,and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway.This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.
基金National Natural Science Foundation of China,Award Number:81801918National Natural Science Foundation of China,Award Number:81772098。
文摘Background:Reconstruction of upper and lower lip subunits is a complicated and elusive challenge.For patients affected by defects involving upper and lower lip subunits,a technique able to reconstruct both aesthetic units with matched colour,sufficient contours and similar texture would be ideal.In this study,we present our experience with upper and lower lip reconstruction using the pre-expanded bipedicled visor flap.Methods:From January 2014 to January 2017,12 male patients presenting with defects of the upper and lower lip subunits were treated using this surgical technique.After a period of expansion of the scalp flap of over 6 months,the bipedicled visor flap was raised from both the parietal regions and rotated to resurface the defect.Delay and section of the pedicle were then performed.Results:Twelve male patients with postburn scars aged 22 to 48 years(mean:34 years)were successfully treated with no major complications.The donor site was closed primarily in all cases.Subsequent flap debulking and minor revisions were performed under local anaesthesia between 6 and 12 months postoperatively.Conclusions:The pre-expanded bipedicled visor flap provides an effective and reliable option for upper and lower lip reconstruction with excellent colour and texture.It is feasible to achieve these results simultaneously from a single donor site by using a pre-expanded bipedicled visor flap.
基金supported by the National Natural Science Foundation of China(grant number:82172222)the Outstanding Professional and Technical Leader Program of the Shanghai Municipal Science and Technology Commission(18XD1423700)+2 种基金the Shanghai Health Industry Clinical Research Special Project(20204Y0443)the Cross Research Project of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202009)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(Grant number:20152227).
文摘Background:An ideal tension-relieving suture should be efficient for>3 months to retrieve normal tensile strength.Most preexisting suturing techniques provided tension elimination followed by relapse and scar proliferation due to absorption and cut-through of the sutures.This study introduces a simple but effective suture technique developed by a senior author(ZYX)to solve this problem.Methods:A total of 120 patients with pathological scar(PS)had intervention treatment with the proposed suturing strategy at three centers from January 2018 to January 2021.A slowly absorbable 2-0 barbed suturewas used for subcutaneous tension relieving with a set-back from the wound edge and a horizontal interval between proposed inserting points of 1 cm.The Patient and Observer Scar Assessment Scale(POSAS),scar width,perfusion and eversion of the wound edge were evaluated at 3-,6-and 12-month follow-up.The time needed to place the tension-relieving suture was recorded and relapse was monitored for 18 months postoperatively.Results:In total,76 trunks,32 extremities and 12 cervical PS were included,with an average subcutaneous tension-relieving suture time of 5 min.The Patient and Observer Scar Assessment Scale(POSAS)score decreased from 84.70±7.06 preoperatively to 28.83±3.09,26.14±1.92 and 24.71±2.00 at 3,6 and 12 months postoperatively,respectively(p<0.0001).The scar widths were 0.17±0.08,0.25±0.09 and 0.33±0.10 cm,respectively,with perfusion significantly decreased from 213.64±14.97 to 112.23±8.18 at 6 months(p<0.0001).The wound edge flattened out during the first 3 months in most cases with only two scar relapses.Conclusions:Zhang’s suture technique provides a rapid and long-lasting tension-relieving effect with ideal scar appearances and lower relapse rates in the surgical management of PS.
基金supported by National Natural Science Foundation of China(82172222 and 82102328)ShanghaiMunicipal Education Commission-Gaofeng Clinical Medicine Grant Support(20152227)+3 种基金ClinicalMulti-Disciplinary Team Research Program of ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(2017-1-007)Cross Research Project of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202009)Shanghai Health Industry Clinical Research Special Project(20204Y0443)Shanghai Municipal Key Clinical Specialty(shslczdzk00901).
文摘Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior.Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation.This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation.Methods:Here,augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts(HFs)and HS tissues,and the suppression of glycolysis also attenuated fibroblast activation.We also introduced IR780,a heptamethine cyanine dye,to regulate glycolysis for the control of HS formation.Results:In vitro,cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs.In vivo,the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation.Furthermore,IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies,and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts.Conclusions:This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.
基金The national natural science foundation of China(Grant Number:81772098)Clinical Multi-Disciplinary Team Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(Grant Number:2017-1-007)+3 种基金Clinical Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(Grant Number:JYLJ027)Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(Grant Number:20152227)The national natural science foundation of China(Grant Number:82000456)Scientific research foundation of Shanghai Municipal Commission of Health and Family Planning(Grant Number:20154Y0023).
文摘Background:Several surgeons have described studies of free-tissue transfers using veins instead of arteries.These innovative microsurgical techniques can offer several advantages,such as an easier dissection during flap harvesting,and represent an alternative during an accidental surgical mistake or development of new surgical procedures.The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer(VLNT)only based on venous blood flow in a mouse model,evaluate their blood flow microcirculation through indocyanine green(ICG)angiography and investigate the lymphatic drainage function and the lymph nodes’structures.Methods:Five types of venous lymph node flaps(LNF)were created and investigated:Types IA,IB,IC,IIA and IIB were developed by ICG intraoperatively(with videos in the article).Seven weeks later,by applying methylene blue,the recanalization of the lymphatic vessels between the LNF and the recipient site was detected.Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis.Results:All of the venous LNFs developed except Type IC.Seven weeks later,methylene blue flowed into Types IA,IB,IIA and IIB from recipient sites.When comparing with arteriovenous lymph node,the medullary sinus was diffusely distributed in venous lymph nodes.The proportion of cells was significantly reduced(p<0.05).The artery diameters were significantly smaller(p<0.05).The veins diameters and lymphatic vessels output in Types IA,IB,IIA and IIB were more dilated(p<0.05).Conclusions:This research demonstrated that Type IA,IB,IIA and IIB venous LNFs can retrogradely receive venous blood supply;they can survive,produce a lymphatic recanalization and integrate with the surrounding tissue,despite lymph node structural changes.Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.
