Correction:Nanomaterial-Based Repurposing of Macrophage Metabolism and Its Applications

Following publication of the original article[1],the authors reported an error in the last author’s name,it was mistakenly written as“Jun Den”.The correct author’s name“Jun Deng”has been updated in this Correction.

Nanomaterial‑Based Repurposing of Macrophage Metabolism and Its Applications

Macrophage immunotherapy represents an emerging therapeutic approach aimed at modulating the immune response to alleviate disease symptoms.Nanomaterials(NMs)have been engineered to monitor macrophage metabolism,enabling the evaluation of disease progression and the replication of intricate physiological signal patterns.They achieve this either directly or by delivering regulatory signals,thereby mapping phenotype to effector functions through metabolic repurposing to customize macrophage fate for therapy.However,a comprehensive summary regarding NM-mediated macrophage visualization and coordinated metabolic rewiring to maintain phenotypic equilibrium is currently lacking.This review aims to address this gap by outlining recent advancements in NM-based metabolic immunotherapy.We initially explore the relationship between metabolism,polarization,and disease,before delving into recent NM innovations that visualize macrophage activity to elucidate disease onset and fine-tune its fate through metabolic remodeling for macrophage-centered immunotherapy.Finally,we discuss the prospects and challenges of NM-mediated metabolic immunotherapy,aiming to accelerate clinical translation.We anticipate that this review will serve as a valuable reference for researchers seeking to leverage novel metabolic intervention-matched immunomodulators in macrophages or other fields of immune engineering.

Epigenetic regulation of macrophage polarization in wound healing

The immune microenvironment plays a critical role in regulating skin wound healing.Macrophages,the main component of infiltrating inflammatory cells,play a pivotal role in shaping the immune microenvironment in the process of skin wound healing.Macrophages comprise the classic proinflammatory M1 subtype and anti-inflammatory M2 population.In the early inflammatory phase of skin wound closure,M1-like macrophages initiate and amplify the local inflammatory response to disinfect the injured tissue.In the late tissue-repairing phase,M2 macrophages are predominant in wound tissue and limit local inflammation to promote tissue repair.The biological function of macrophages is tightly linked with epigenomic organization.Transcription factors are essential for macrophage polarization.Epigenetic modification of transcription factors determines the heterogeneity of macrophages.In contrast,transcription factors also regulate the expression of epigenetic enzymes.Both transcription factors and epigenetic enzymes form a complex network that regulates the plasticity of macrophages.Here,we describe the latest knowledge concerning the potential epigenetic mechanisms that precisely regulate the biological function of macrophages and their effects on skin wound healing.

Mitochondrial dysfunction and mitophagy:crucial players in burn trauma and wound healing

Burn injuries are a significant cause of death worldwide,leading to systemic inflammation,multiple organ failure and sepsis.The progression of burn injury is explicitly correlated with mitochondrial homeostasis,which is disrupted by the hyperinflammation induced by burn injury,leading to mitochondrial dysfunction and cell death.Mitophagy plays a crucial role in maintaining cellular homeostasis by selectively removing damaged mitochondria.A growing body of evidence from various disease models suggest that pharmacological interventions targeting mitophagy could be a promising therapeutic strategy.Recent studies have shown that mitophagy plays a crucial role in wound healing and burn injury.Furthermore,chemicals targeting mitophagy have also been shown to improve wound recovery,highlighting the potential for novel therapeutic strategies based on an in-depth exploration of the molecular mechanisms regulating mitophagy and its association with skin wound healing.

Efficacy and safety of extracorporeal membrane oxygenation for burn patients: a comprehensive systematic review and meta-analysis

Background:Respiratory and circulatory dysfunction are common complications and the leading causes of death among burn patients,especially in severe burns and inhalation injury.Recently,extracorporeal membrane oxygenation(ECMO)has been increasingly applied in burn patients.However,current clinical evidence is weak and conflicting.This study aimed to comprehensively evaluate the efficacy and safety of ECMO in burn patients.Methods:A comprehensive search of PubMed,Web of Science and Embase from inception to 18 March 2022 was performed to identify clinical studies on ECMO in burn patients.The main outcome was in-hospital mortality.Secondary outcomes included successful weaning from ECMO and complications associated with ECMO.Meta-analysis,meta-regression and subgroup analyses were conducted to pool the clinical efficacy and identify influencing factors.Results:Fifteen retrospective studies with 318 patients were finally included,without any control groups.The commonest indication for ECMO was severe acute respiratory distress syndrome(42.1%).Veno-venous ECMO was the commonest mode(75.29%).Pooled in-hospital mortality was 49%[95%confidence interval(CI)41-58%]in the total population,55%in adults and 35%in pediatrics.Meta-regression and subgroup analysis found that mortality significantly increased with inhalation injury but decreased with ECMO duration.For studies with percentage inhalation injury≥50%,pooled mortality(55%,95%CI 40-70%)was higher than in studies with percentage inhalation injury<50%(32%,95%CI 18-46%).For studies with ECMO duration≥10 days,pooled mortality(31%,95%CI 20-43%)was lower than in studies with ECMO duration<10 days(61%,95%CI 46-76%).In minor and major burns,pooled mortality was lower than in severe burns.Pooled percentage of successful weaning from ECMO was 65%(95%CI 46-84%)and inversely correlated with burn area.The overall rate of ECMO-related complications was 67.46%,and infection(30.77%)and bleedings(23.08%)were the two most common complications.About 49.26%of patients required continuous renal replacement therapy.Conclusions:ECMO seems to be an appropriate rescue therapy for burn patients despite the relatively high mortality and complication rate.Inhalation injury,burn area and ECMO duration are the main factors influencing clinical outcomes.

The m6A reader YTHDF2 alleviates the inflammatory response by inhibiting IL-6R/JAK2/STAT1 pathway-mediated high-mobility group box-1 release

Background:Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation.YTH domain family 2(YTHDF2),a wellstudied N6-methyladenosine(m6A)reader that specifically recognizes and binds to m6A-modified transcripts to mediate their degradation,is connected to pathogenic and physiological processes in eukaryotes,but its effect on sepsis is still unknown.We aimed to discover the effects and mechanisms of YTHDF2 in sepsis.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and western blot analyses were used to measure the expression of YTHDF2,the interleukin 6 receptor(IL-6R),high-mobility group box-1(HMGB1),Janus kinase 2(JAK2)and signal transducer and activator of transcription 1(STAT1)under different in vitro conditions.Enzyme-linked immunosorbent assays were utilized to evaluate the expression of HMGB1,IL-6,IL-1βand tumor necrosis factor-α.To confirm that YTHDF2 specifically targets IL-6R mRNA,RNA immunoprecipitation and dual-luciferase reporter assays were performed.Finally,we utilized a mouse model of lipopolysaccharide(LPS)-induced sepsis to verify the effects of YTHDF2 in vivo.Results:According to our findings,YTHDF2 was expressed at a low level in peripheral blood mononuclear cells from septic mice and patients as well as in LPS-induced RAW264.7 cells.Overexpression of YTHDF2 alleviated the inflammatory response by inhibiting HMGB1 release and JAK2/STAT1 signalling in LPS-stimulated cells.Mechanistically,YTHDF2 suppressed JAK2/STAT1 signalling by directly recognizing the m6A-modified site in IL-6R and decreasing the stability of IL-6R mRNA,thereby inhibiting HMGB1 release.In vivo experiments showed that YTHDF2 played a protective role in septic mice by suppressing the IL-6R/JAK2/STAT1/HMGB1 axis.Conclusions:In summary,these findings demonstrate that YTHDF2 plays an essential role as an inhibitor of inflammation to reduce the release of HMGB1 by inhibiting the IL-6R/JAK2/STAT1 pathway,indicating that YTHDF2 is a novel target for therapeutic interventions in sepsis.

A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms

Background:Multidrug-resistant(MDR)gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality.Moreover,the formation of biofilms makes these bacteria difficult to control.Therefore,developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed.The purpose of this study was to develop a multifunctional nanoassembly(IRNB)based on IR-780 and N,N-di-sec-butyl-N,N-dinitroso-1,4-phenylenediamine(BNN6)for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.Methods:The characterization and bacteria-targeting ability of IRNB were investigated.The bac-tericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay,plate counting method and live/dead staining in vitro.The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo.A cell counting kit-8 assay,Calcein/PI cytotoxicity assay,hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.Results:Herein,we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy(PTT),photodynamic therapy(PDT)and nitric oxide(NO)effect triggered by an 808 nm laser.This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect.Upon irradiation with an 808 nm laser,IRNB was activated and produced both reactive oxygen species(ROS)and hyperthermia.The local hyperthermia could induce NO generation,which further reacted with ROS to generate ONOO−,leading to the enhancement of bactericidal efficacy.Furthermore,NO and ONOO−could disrupt the cell membrane,which converts bacteria to an extremely susceptible state and further enhances the photothermal effect.In this study,IRNB showed a superior photothermal-photodynamic-chemo(NO)synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.This resulted in effective control of associated infections,relief of inflammation,promotion of re-epithelization and collagen deposition,and regulation of angiogenesis during wound healing.Moreover,IRNB exhibited excellent biocompatibility,both in vitro and in vivo.Conclusions:The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells

Background:Burn wound healing is a complex process and the role of Wnt ligands varies in this process.Whether and how Wnt4 functions in burn wound healing is not well understood.In this study,we aim to reveal the effects and potential mechanisms of Wnt4 in burn wound healing.Methods:First,the expression of Wnt4 during burn wound healing was determined by immunoflu-orescence,Western blotting and qPCR.Then,Wnt4 was overexpressed in burn wounds.The healing rate and healing quality were analysed by gross photography and haematoxyline and eosin staining.Collagen secretion was observed by Masson staining.Vessel formation and fibroblast distribution were observed by immunostaining.Next,Wnt4 was knocked down in HaCaT cells.The migration of HaCaT cells was analysed by scratch healing and transwell assays.Next,the expression ofβ-catenin was detected by Western blotting and immunofluorescence.The binding of Frizzled2 and Wnt4 was detected by coimmunoprecipitation and immunofluorescence.Finally,the molecular changes induced by Wnt4 were analysed by RNA sequencing,immunofluorescence,Western blotting and qPCR in HaCaT cells and burn wound healing tissues.Results:The expression of Wnt4 was enhanced in burn wound skin.Overexpression of Wnt4 in burn wound skin increased the thickness of epidermis.Collagen secretion,vessel formation and fibroblast distribution were not significantly impacted by Wnt4 overexpression.When Wnt4 was knocked down in HaCaT cells,the ratio of proliferating cells decreased,the ratio of apoptotic cells increased and the ratio of the healing area in the scratch healing assay to the number of migrated cells in the transwell assay decreased.The nuclear translocation ofβ-catenin decreased in shRNA of Wnt4 mediated by lentivirus-treated HaCaT cells and increased in Wnt4-overexpressing epidermal cells.RNA-sequencing analysis revealed that cell junction-related signalling pathways were significantly impacted by Wnt4 knockdown.The expression of the cell junction proteins was decreased by the overexpression of Wnt4.Conclusions:Wnt4 promoted the migration of epidermal cells.Overexpression of Wnt4 increased the thickness of the burn wound.A potential mechanism for this effect is that Wnt4 binds with Frizzled2 and increases the nuclear translocation ofβ-catenin,thus activating the canonical Wnt signalling pathway and decreasing the cell junction between epidermal cells.

Consensus on the application of negative pressure wound therapy of diabetic foot wounds

Because China is becoming an aging society,the incidence of diabetes and diabetic foot have been increasing.Diabetic foot has become one of the main health-related killers due to its high disability and mortality rates.Negative pressure wound therapy(NPWT)is one of the most effective techniques for the treatment of diabetic foot wounds and great progress,both in terms of research and its clinical application,has been made in the last 20 years of its development.However,due to the complex pathogenesis and management of diabetic foot,irregular application of NPWT often leads to complications,such as infection,bleeding and necrosis,that seriously affect its treatment outcomes.In 2020,under the leadership of Burns,Trauma and Tissue Repair Committee of the Cross-Straits Medicine Exchange Association,the writing group for‘Consensus on the application of negative pressure wound therapy of diabetic foot wounds’was established with the participation of scholars from the specialized areas of burns,endocrinology,vascular surgery,orthopedics and wound repair.Drawing on evidence-based practice suggested by the latest clinical research,this consensus proposes the best clinical practice guidelines for the application and prognostic evaluation of NPWT for diabetic foot.The consensus aims to support the formation of standardized treatment schemes that clinicians can refer to when treating cases of diabetic foot.

Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study were to comprehensively examine the effectiveness,synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.Methods:Full-thickness wounds were made on the back of C57/BL6 mice.PRP or saline solution as a control was administered to the wound area.Wound healing rate,local inflammation,angiogenesis,re-epithelialization and collagen deposition were measured at days 3,5,7 and 14 after skin injury.The biological character of epidermal stem cells(ESCs),which reflect the potential for re-epithelialization,was further evaluated in vitro and in vivo.Results:PRP strongly improved skin wound healing,which was associated with regulation of local inflammation,enhancement of angiogenesis and re-epithelialization.PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β.An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1.Moreover,PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs,and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.Conclusion:PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization.However,the underlying regulatory mechanism needs to be investigated in the future.Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

Construction of heparin-based hydrogel incorporated with Cu_(5.4)O ultrasmall nanozymes for wound healing and inflammation inhibition

Excessive production of inflammatory chemokines and reactive oxygen species(ROS)can cause a feedback cycle of inflammation response that has a negative effect on cutaneous wound healing.The use of wound-dressing materials that simultaneously absorb chemokines and scavenge ROS constitutes a novel‘weeding and uprooting’treatment strategy for inflammatory conditions.In the present study,a composite hydrogel comprising an amine-functionalized star-shaped polyethylene glycol(starPEG)and heparin for chemokine sequestration as well as Cu_(5.4)O ultrasmall nanozymes for ROS scavenging(Cu_(5.4)O@Hep-PEG)was developed.The material effectively adsorbs the inflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8,decreasing the migratory activity of macrophages and neutrophils.Furthermore,it scavenges the ROS in wound fluids to mitigate oxidative stress,and the sustained release of Cu_(5.4)O promotes angiogenesis.In acute wounds and impaired-healing wounds(diabetic wounds),Cu_(5.4)O@Hep-PEG hydrogels outperform the standard-of-care product Promogram®in terms of inflammation reduction,increased epidermis regeneration,vascularization,and wound closure.

Joint contractures in severe burn patients with early rehabilitation intervention in one of the largest burn intensive care unit in China:a descriptive analysis

Background:Joint contracture is the major clinical complication in burn patients,especially,the severe burn patients.This study aimed to investigate the number and severity of joint contractures in patients with burns affecting greater than or equal to 50%of the total body surface area(TBSA)undergoing early rehabilitation in a burn intensive care unit(BICU).Methods:We analyzed burn patients with burns affecting greater than or equal to 50%of the TBSA admitted to a BICU who received early rehabilitation within 7 days post-injury from January 2011 to December 2015.Demographic and medical information was collected.The range of motion(ROM)of different joints was measured 1 month post-admission.Spearman’s correlation coefficient and logistic regression analysis was used to determine predictors of the presence and severity of contractures.Result:The average affected TBSA of the included burn patients was 67.4%,and the average length of stay in the BICU was 46.2±28.8 days.One hundred and one of 108 burn patients(93.5%)developed at least one joint contracture.The ROM in 67.9%of the affected joints was mildly limited.The majority of contractures in severe burn patients were mild(37.7%)or moderate(33.2%).The wrist was the most commonly affected joint(18.2%),followed by the shoulder,ankle,hip,knee,and elbow.A predictor of the presence of contractures was the length of hospital stay(p=0.049).The severe contracture was related to the area of full-thickness burns,the strict bed rest time,and the duration of rehabilitation in BICU.The length of rehabilitation stay(days)in patients with moderate contracture is 54.5%longer than that in severe contracture(p=0.024)Conclusion:During the long stay in BICU,the length of rehabilitation stay in a BICU could decrease the severity of contractures from severe to moderate in the patients with equal to 50%of the TBSA.Hence,this research reveals the important role of early rehabilitation interventions in severe burn patients.

Guidelines for burn rehabilitation in China

Quality of life and functional recovery after burn injury is the final goal of burn care,especially as most of burn patients survive the injury due to advanced medical science.However,dysfunction,disfigurement,contractures,psychological problems and other discomforts due to burns and the consequent scars are common,and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients.This guideline,organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment,which is suitable for the current medical circumstances of China.It can be used as the start of the tools for burn rehabilitation.

Extracorporeal membrane oxygenation combined with continuous renal replacement therapy for the treatment of severe burns:current status and challenges

Severe burns often cause various systemic complications and multiple organ dysfunction syndrome,which is the main cause of death.The lungs and kidneys are vulnerable organs in patients with multiple organ dysfunction syndrome after burns.Extracorporeal membrane oxygenation(ECMO)and continuous renal replacement therapy(CRRT)have been gradually applied in clinical practice and are beneficial for severe burn patients with refractory respiratory failure or renal dysfunction.However,the literature on ECMO combined with CRRT for the treatment of severe burns is limited.Here,we focus on the current status of ECMO combined with CRRT for the treatment of severe burns and the associated challenges,including the timing of treatment,nutrition support,heparinization and wound management,catheter-related infection and drug dosing in CRRT.With the advancement of medical technology,ECMO combined with CRRT will be further optimized to improve the outcomes of patients with severe burns.

Photodynamic therapy accelerates skin wound healing through promoting re-epithelialization

Background:Epidermal stem cells(EpSCs)that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis.Little is known about the effects of photochemical activation on EpSC differentiation,proliferation and migration during wound healing.The present study aimed to determine the effects of photodynamic therapy(PDT)on wound healing in vivo and in vitro.Methods:We created mouse full-thickness skin resection models and applied 5-aminolevulinic acid(ALA)for PDT to the wound beds.Wound healing was analysed by gross evaluation and haematoxylin–eosin staining in vivo.In cultured EpSCs,protein expression was measured using flow cytometry and immunohistochemistry.Cell migration was examined using a scratch model;apoptosis and differentiation were measured using flow cytometry.Results:PDT accelerated wound closure by enhancing EpSC differentiation,proliferation and migration,thereby promoting re-epithelialization and angiogenesis.PDT inhibited inflammatory infiltration and expression of proinflammatory cytokines,whereas the secretion of growth factors was greater than in other groups.The proportion of transient amplifying cells was significantly greater in vivo and in vitro in the PDT groups.EpSC migration was markedly enhanced after ALAinduced PDT.Conclusions:Topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization,promoting angiogenesis as well as modulating skin homeostasis.This work provides a preliminary theoretical foundation for the clinical administration of topical ALA-induced PDT in skin wound healing.

A ROS-responsive,self-immolative and self-reporting hydrogen sulfide donor with multiple biological activities for the treatment of myocardial infarction

Myocardial infarction(MI),as one of the leading causes of global death,urgently needs effective therapies.Recently,hydrogen sulfide(H2S)has been regarded as a promising therapeutic agent for MI,while its spatiotemporally controlled delivery remains a major issue limiting clinical translation.To address this limitation,we designed and synthesized a novel H2S donor(HSD-R)that can produce H2S and emit fluorescence in response to reactive oxygen species(ROS)highly expressed at diseased sites.HSD-R can specifically target mitochondria and provide red fluorescence to visualize and quantify H2S release in vitro and in vivo.Therapeutically,HSD-R significantly promoted the reconstruction of cardiac structure and function in a rat MI model.Mechanistically,myocardial protection is achieved by reducing cardiomyocyte apoptosis,attenuating local inflammation,and promoting angiogenesis.Furthermore,inhibition of typical pro-apoptotic genes(Bid,Apaf-1,and p53)played an important role in the anti-apoptotic effect of HSD-R to achieve cardioprotection,which were identified as new therapeutic targets of H2S against myocardial ischemia injury.This ROS-responsive,self-immolative,and fluorescent H2S donor can serve as a new theranostic agent for MI and other ischemic diseases.

P311 promotes typeⅡtransforming growth factor-βreceptor mediated fibroblast activation and granulation tissue formation in wound healing

Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.

Epidemiological and clinical characteristics of burns in the older person:a seven-year retrospective analysis of 693 cases at a burn center in south-west China

Background:Burns are one of the major traumas that may affect older individuals.The purpose of this study was to investigate the epidemiological and clinical characteristics of geriatric burns at a major center in south-west China.Methods:This retrospective study was conducted at the Institute of Burn Research,Southwest Hospital of Army Medical University between 2010 and 2016,and the data collected from medical records included admission date,age,gender,premorbid disease,burn etiology,injured anatomical location,burn area and depth,inhalation injury,number of surgeries,length of stay(LOS),clinical outcome,and medical cost.Results:Of the 693 older burn patients included,60.75%were male and 56.85%were aged 60–69 years.Burns peaked in December–March and June.Flamewas the most common cause of burns,making up 51.95%of all cases,and also dominated in the burn patients aged 60–69 years.Limbs were the most common anatomical sites of burns(69.41%),and the median total body surface area(TBSA)was 5%(interquartile range[IQR]:2%–15%).The percentage of the patients who underwent surgeries and number of surgeries significantly increased in the cases of contact burns,younger age and full-thickness burns.Six deaths resulted in a mortality of 0.9%.The median LOSwas 16 days(IQR:8–29 days),and the main risk factors were more surgeries,better outcomes,and full-thickness burns.The median costwas 20,228 CNY(IQR:10,457–46,581.5 CNY),and major risk factors included longer LOS,larger TBSA,and more surgeries.Furthermore,compared to the earlier data from our center,the proportion of older adults among all burns(7.50%vs.4.15%),proportion of flame burns(51.95%vs.33.90%),and mean age(69.05 years vs.65.10 years)were significantly higher,while the proportion of premorbidities(16.9%vs.83.9%),mortality(0.9%vs.7.5%)and median TBSA(5%vs.21%)were significantly lower.Conclusions:This study suggested that closer attention should be paid to prevent burn injuries in older people aged 60–69 years,especially males,regarding incidents in the summer and winter,and flame burns.Moreover,tailored intervention strategies based on related risk factors should be under special consideration.

Comparative proteomic analysis of extracellular matrix proteins secreted by hypertrophic scar witb normal skin fibroblasts

The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) during wound healing, associated with cosmetic, functional, and psychological problems. Owing to the role of ECM proteins in scar formation, we comparatively analyzed matrix proteins secreted by normal skin fibroblasts (NSFs) and HS fibroblasts (HSFs). The acetone-extracted secreted proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and identified by mass spectrometry (MS). Based on Go annotation of MS data, the profiling of ECM proteins was established and scar-related proteins have been screened out. The functions of several ECM proteins identified by MS have been discussed, such as collagens I, VI, XII, fibronectin, decorin, lumican, and protein procollagen C endopeptidase enhancer 1 (PCPE-1). Among them, the MS result of PCPE-1 was supported by Western blotting that PCPE-1 from HSFs were significantly upregulated than that from NSFs. It is suggested that PCPE-1 could be a potential target for scar treatment. The exploration of scar related proteins may provide new perspectives on understanding the mechanism of scar formation and open a new way to scar treatment and prevention.

Mixed lymphocyte reaction induced by multiple alloantigens and the role for IL-10 in proliferation inhibition

The frequency of T cells that can respond to alloantigens is unusually high.It remains unclear how T cells would respond when stimulated by multiple major histocompatibility complex(MHC)disparate alloantigens in the same cultures.In this report,we examined potential interactions of T cell clones that were stimulated simultaneously by two sets of complete MHC disparate alloantigens using mixed lymphocyte reaction(MLR).In this assay,we observed that proliferation of B6 lymphocytes(H-2b)stimulated by both BALB/c(H-2d)and C_(3)H(H-2k)allogeneic cells was not increased but rather reduced as compared to B6 cells stimulated with either BALB/c or C_(3)H allogeneic cells.Interestingly,interleukin(IL)-10 expressions at both protein level and mRNA level was signifi cantly increased in cultures stimulated with the two MHC alloantigens,while IL-2,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β1 production did not show any differences.In addition,Foxp_(3) mRNA expression was comparable amongst all groups.In conclusion,we observed an inhibitory effect in T cell proliferation in response to multiple MHC mismatched alloantigens in MLR,and this effect might be associated with the upregulation of IL-10 expression.