Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

Advancing antimicrobial strategies for managing oral biofilm infections

Effective control of oral biofilm infectious diseases represents a major global challenge.Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells.The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years.Antimicrobial dental materials based on antimicrobial agent release,contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface.Among the therapeutic approaches for managing biofilms in clinical practice,antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms,and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches.Nevertheless,more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data.The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.

Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids

Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.

Do cardiopulmonary resuscitation real-time audiovisual feedback devices improve patient outcomes? A systematic review and metaanalysis

BACKGROUND Cardiac arrest is a leading cause of mortality in America and has increased in the incidence of cases over the last several years.Cardiopulmonary resuscitation(CPR)increases survival outcomes in cases of cardiac arrest;however,healthcare workers often do not perform CPR within recommended guidelines.Real-time audiovisual feedback(RTAVF)devices improve the quality of CPR performed.This systematic review and meta-analysis aims to compare the effect of RTAVF-assisted CPR with conventional CPR and to evaluate whether the use of these devices improved outcomes in both in-hospital cardiac arrest(IHCA)and out-of-hospital cardiac arrest(OHCA)patients.AIM To identify the effect of RTAVF-assisted CPR on patient outcomes and CPR quality with in-and OHCA.METHODS We searched PubMed,SCOPUS,the Cochrane Library,and EMBASE from inception to July 27,2020,for studies comparing patient outcomes and/or CPR quality metrics between RTAVF-assisted CPR and conventional CPR in cases of IHCA or OHCA.The primary outcomes of interest were return of spontaneous circulation(ROSC)and survival to hospital discharge(SHD),with secondary outcomes of chest compression rate and chest compression depth.The methodo-logical quality of the included studies was assessed using the Newcastle-Ottawa scale and Cochrane Collaboration’s“risk of bias”tool.Data was analyzed using R statistical software 4.2.0.results were statistically significant if P<0.05.RESULTS Thirteen studies(n=17600)were included.Patients were on average 69±17.5 years old,with 7022(39.8%)female patients.Overall pooled ROSC in patients in this study was 37%(95%confidence interval=23%-54%).RTAVF-assisted CPR significantly improved ROSC,both overall[risk ratio(RR)1.17(1.001-1.362);P=0.048]and in cases of IHCA[RR 1.36(1.06-1.80);P=0.002].There was no significant improvement in ROSC for OHCA(RR 1.04;0.91-1.19;P=0.47).No significant effect was seen in SHD[RR 1.04(0.91-1.19);P=0.47]or chest compression rate[standardized mean difference(SMD)-2.1;(-4.6-0.5);P=0.09].A significant improvement was seen in chest compression depth[SMD 1.6;(0.02-3.1);P=0.047].CONCLUSION RTAVF-assisted CPR increases ROSC in cases of IHCA and chest compression depth but has no significant effect on ROSC in cases of OHCA,SHD,or chest compression rate.

玻璃体和通用型复合树脂耐磨性的临床对照研究

目的:采用激光三维扫描技术评估玻璃体和通用型复合树脂用于后牙充填的耐磨性。方法:根据纳入标准选取48名患者共108颗患牙(每组各54颗),随机分配用玻璃体(BeautifilⅡ,简称BF)或通用型复合树脂(Filtek Z350,简称Z350)进行充填。分别于术后1周、6个月、18个月和4年,采用改良美国公共卫生署(United States Public Health Service,USPHS)标准对充填体进行临床评价并拍照和制取模型。使用激光三维扫描仪扫描模型后,对图像进行配准和计算磨耗深度,使用SPSS 20.0进行统计分析。结果:术后4年回访43名患者,回访率为89.6%。BF组和Z350组各有4例和3例出现脱落、继发龋、充填体折断和牙髓坏死。两组充填体的4年存留率均为95.8%,符合美国牙医协会(American Dental Association,ADA)标准(3年存留率>90%)。0~6个月两组充填体的磨耗速率最快,随后磨耗速率的下降趋于平缓,BF组4年总磨耗深度为(58±22)μm,Z350组为(54±16)μm(P>0.05),耐磨性均符合ADA标准(3年磨耗深度<100μm)。两组充填体均表现为围绕咬合接触区形成凹坑状磨耗(Ⅰ型)和充填体发生均匀磨耗(Ⅱ型)。术后4年,Ⅰ型磨耗充填体中,BF组的磨耗深度大于Z350组(P<0.05),Ⅱ型磨耗充填体中,两组间差异无统计学意义(P>0.05)。结论:玻璃体的4年存留率和耐磨性均符合ADA标准,用于后牙牙合面重咬合接触区时,玻璃体的耐磨性略逊于复合树脂,用于非重咬合接触区时,二者间无明显差异。

不同椅旁可切削修复材料序列抛光时间及表面粗糙度与光泽度的比较

目的:比较不同种类计算机辅助设计/辅助制作(computer aided design/manufacturing,CAD/CAM)修复材料抛光后表面粗糙度值(Ra值)与光泽度值的差异,测定适宜的抛光时间,为操作者抛光椅旁可切削修复体提供参考。方法:选择5种不同种类CAD/CAM修复材料长石瓷(vita markⅡ,VM)、弹性瓷(vita enamic,VE)、优韧瓷(lava ulimate,LU)、复合树脂A(shofu block HC,SB)和复合树脂B(brilliant crios,BC),每种材料制备6个试样,共30个试样。将试样固定于自制抛光装置,使用Sof-Lex抛光碟系统中的中碟(medium disk,M碟,磨粒粒径10~40μm)、细碟(fine disk,F碟,磨粒粒径3~9μm)和超细碟(superfine disk,SF碟,磨粒粒径1~7μm)依次对试样进行序列抛光。试样每抛光10 s测量一次Ra值及光泽度值,数值不再变化时更换下一级抛光碟,每个抛光碟仅使用一次。更换下一级抛光碟的同时记录试样的Ra值、光泽度值以及抛光时间,实验完成后用SPSS 24.0软件进行统计学分析。结果:序列抛光后所有材料Ra值较抛光前显著降低(P<0.05),光泽度值显著升高(P<0.05)。不同材料间的Ra值差异无统计学意义(P>0.05),而LU的光泽度值[(68.1±4.5)GU]与SB的光泽度值[(68.2±5.8)GU]显著高于VE[(48.1±8.1)GU]与BC[(53.2±5.8)GU],P<0.05。达到最佳Ra值和光泽度值,VM[40(30,55)s]所需总抛光时间最短,VE[140(135,145)s]、LU[130(120,140)s]、SB[140(130,150)s]与BC[130(120,140)s]的抛光时间差异无统计学意义。结论:所有CAD/CAM修复材料经Sof-Lex抛光碟系统序列抛光后均能显著降低表面粗糙度值和提高光泽度值;不同材料达到最佳表面粗糙度和光泽度所需的抛光时间不同;推荐使用Sof-Lex系统抛光时,对于长石瓷,仅用M碟抛光40 s即可。对于弹性瓷、优韧瓷、复合树脂A与复合树脂B,要序列使用M碟、F碟和SF碟抛光,总体抛光时间约130~140 s。

髓腔内压对树脂水门汀与牙本质粘接强度的影响

目的:评价髓腔内压条件对树脂水门汀与牙本质微拉伸粘接强度的影响。方法:选择新拔除的人无龋第三磨牙30颗分成2组,去除咬合面釉质制备牙本质平面,选取剩余牙本质厚度为0.5~2.5 mm的牙本质试样,在有染料的髓腔内压条件下,观察牙本质表面与牙面处理剂Single Bond Universal(SBU)固化后表面在即刻、5 min、30min、2 h的染料渗透情况。保持最小剩余牙本质厚度为(1.0±0.1)mm,分别在有或无髓腔内压条件(15或0cm H2O,1 cm H2O=0.098 k Pa)下维持30 min,使用SBU并光照固化,然后使用模具在牙本质表面堆塑Rely X Ultimate(RLX)树脂水门汀(直径10 mm,高4 mm),制备牙本质-树脂水门汀粘接试样。试样在37℃蒸馏水中储存24 h后,将牙本质-树脂水门汀试样垂直于粘接界面切割形成横截面积为0.9 mm×0.9 mm条状试样,使用微拉伸测试仪测试计算其粘接强度(两独立样本t检验,双侧检验水平α=0.05),用扫描电镜观察统计试样断裂类型(Fisher精确检验,双侧检验水平α=0.05)。将牙本质-树脂水门汀试样垂直粘接界面做切片,厚度0.8 mm,扫描电镜下观察粘接界面形貌。结果:在髓腔内压条件下,随时间延长,粘接表面染料渗出增加。有髓腔内压时和无髓腔内压时RLX与牙本质微拉伸粘接强度分别为:(26.26±9.78)MPa和(28.70±9.09)MPa,两者差异无统计学意义(P>0.05)。两组试样断裂类型无明显差异(P>0.05),都以混合断裂为主。两组试样粘接界面可见4~8μm指状树脂突,分布及长短较均匀,形貌无明显差异。结论:SBU预处理牙本质后,髓腔内压不影响树脂水门汀RLX的即刻牙本质粘接强度。

A novel dentin bonding scheme based on extrafibrillar demineralization combined with covalent adhesion using a dry-bonding technique

Dentin bonding is a dynamic process that involves the penetration of adhesive resin monomers into the extrafibrillar and intrafibrillar demineralized collagen matrix using a wet-bonding technique.However,adhesive resin monomers lack the capacity to infiltrate the intrafibrillar space,and the excess water that is introduced by the wet-bonding technique remains at the bonding interface.This imperfectly bonded interface is inclined to hydrolytic degradation,severely jeopardizing the longevity of bonded clinical restorations.The present study introduces a dentin bonding scheme based on a dry-bonding technique,combined with the use of extrafibrillar demineralization and a collagen-reactive monomer(CRM)-based adhesive(CBA).Selective extrafibrillar demineralization was achieved using 1-wt%high-molecular weight(MW)carboxymethyl chitosan(CMCS)within a clinically acceptable timeframe to create a less aggressive bonding substance for dentin bonding due to its selectively extrafibrillar demineralization capacity.CMCS demineralization decreased the activation of in situ collagenase,improved the shrinking resistance of demineralized collagen,and thus provided stronger and more durable bonding than traditional phosphoric acid etching.The new dentin bonding scheme that contained CMCS and CBA and used a dry-bonding technique achieved an encouraging dentin bonding strength and durability with low technical sensitivity.This bonding scheme can be used to improve the stability of the resin-dentin interface and foster the longevity of bonded clinical restorations.

Polyphosphate-crosslinked collagen scaffolds for hemostasis and alveolar bone regeneration after tooth extraction

Post-extraction bleeding and alveolar bone resorption are the two frequently encountered complications after tooth extraction that result in poor healing and rehabilitation difficulties.The present study covalently bonded polyphosphate onto a collagen scaffold(P-CS)by crosslinking.The P-CS demonstrated improved hemostatic property in a healthy rat model and an anticoagulant-treated rat model.This improvement is attributed to the increase in hydrophilicity,increased thrombin generation,platelet activation and stimulation of the intrinsic coagulation pathway.In addition,the P-CS promoted the in-situ bone regeneration and alveolar ridge preservation in a rat alveolar bone defect model.The promotion is attributed to enhanced osteogenic differentiation of bone marrow stromal cells.Osteogenesis was improved by both polyphosphate and blood clots.Taken together,P-CS possesses favorable hemostasis and alveolar ridge preservation capability.It may be used as an effective treatment option for post-extraction bleeding and alveolar bone loss.Statement of significance:Collagen scaffold is commonly used for the treatment of post-extraction bleeding and alveolar bone loss after tooth extraction.However,its application is hampered by insufficient hemostatic and osteoinductive property.Crosslinking polyphosphate with collagen produces a modified collagen scaffold that possesses improved hemostatic performance and augmented bone regeneration potential.

Biomaterial scaffolds for clinical procedures in endodontic regeneration

Regenerative endodontic procedures have been rapidly evolving over the past two decades and are employed extensively in clinical endodontics.These procedures have been perceived as valuable adjuvants to conventional strategies in the treatment of necrotic immature permanent teeth that were deemed to have poor prognosis.As a component biological triad of tissue engineering(i.e.,stem cells,growth factors and scaffolds),biomaterial scaffolds have demonstrated clinical potential as an armamentarium in regenerative endodontic procedures and achieved remarkable advancements.The aim of the present review is to provide a broad overview of biomaterials employed for scaffolding in regenerative endodontics.The favorable properties and limitations of biomaterials organized in naturally derived,host-derived and synthetic material categories were discussed.Preclinical and clinical studies published over the past five years on the performance of biomaterial scaffolds,as well as current challenges and future perspectives for the application of biomaterials for scaffolding and clinical evaluation of biomaterial scaffolds in regenerative endodontic procedures were addressed in depth.

Maternal milk ILCs and adaptive immune cells populate neonatal organs

How does the neonatal immune system decide which of the millions and millions of microbes it encounters during and soon after birth are commensal and which are pathological?This is not a trivial issue.Excessively vigorous responses to commensal bacteria cause unnecessary collateral tissue damage and loss of the potentially beneficial microbial flora needed for host metabolism.On the other hand,insufficient immune defense against invading,harmful,microbes is also very problematic,if not lethal.1 While the mechanisms for self-tolerance have been the subject of extensive investigations since the mid-1950s,such is not the case for selective unresponsiveness to commensal microbial flora residing on the skin or the mucosa of the gastrointestinal track.

Engineered extracellular vesicles:Regulating the crosstalk between the skeleton and immune system

Osteoimmunology has gained momentum in recent years,focusing on the crosstalk between the skeleton and the immune system.Extracellular vesicles(EVs)are nanoscale vesicles that are potential candidates for cell-free tissue regeneration strategies.They may be used for repairing damaged tissues and regulating the body’s immune system and bone-related metabolic activities.Because of the ability of EVs to deliver bioactive signals and mediate intercellular communication,they can decipher the complex mechanisms of interaction within the“osteoimmune system”at the molecular level.To address the lack of targeting ability caused by vesicle heterogeneity in the clinical applications of EVs,these nanoscopical entities may be modified by bioengineering techniques to optimize the interaction between bone repair and immunomodulation for improving treatment efficacy,specificity and safety.In the present review,the endogenous properties that make EVs natural delivery agents are outlined.Properties that may be improved by bioengineering are highlighted.The therapeutic applications of EVs in the rehabilitation of bone defects are discussed.The opportunities and challenges that need to be addressed for translating this field of research into clinical practice are brought into perspectives.