Total knee arthroplasty for treatment of post-traumatic arthritis: Systematic review

AIM To review and report functional outcomes, complications,and survivorship associated with total knee arthroplasty(TKA) in the treatment of post-traumatic arthritis(PTA).METHODS We conducted a systematic review according to the PRISMA guidelines. We searched PubMed, Cochrane Library, and SCOPUS in December 2015 for Englishlanguage clinical research studies, both prospective and retrospective, examining the use of TKA for the treatment of PTA. All relevant articles were accessed in full. The manual search included references of retrieved articles.We extracted data on patients' demographics and clinical outcomes, including preoperative diagnosis and pre- and post-operative functional scores. We summarized the data and reported the results in tables and text.RESULTS Sixteen studies, four prospective and ten retrospective,examined patients who underwent TKA for PTA due to fractures of the proximal tibia, patella, and/or distal femur. Eleven studies utilized the Knee Society Scores criteria to assess functional outcomes. All studies utilizing these criteria reported an improvement in functional and knee scores of patients following TKA. Further, studies reported an increased range of motion(ROM) and reduction of pain following surgery. The most commonly reported complications with TKA included infection, stiffness, wound complications, intraoperative rupture of tendons, and osteolysis/polyethylene wear. The overwhelming majority of these complications occurred within the first two years following surgery. Six studies examined the survivorship of TKA with subsequent revision for any reason as an endpoint. Compared to patients with osteoarthritis, patients with PTA required more revisions, the majority for polyethylene wear.CONCLUSION Although associated with higher complication rates,TKA is an effective treatment for PTA, as it improves ROM, pain and functional outcomes.

Initial effects of inflammation-related cytokines and signaling pathways on the pathogenesis of post-traumatic osteoarthritis

The main pathological change in post-traumatic osteoarthritis （PTOA） is cartilage degeneration, which is closely related to inflammation and oxidative stress. Inflammation can cause degeneration of articular cartilage. Cartilage degeneration can also stimulate the progression of inflammation. It has been found that inflammatory cytokines can participate in the pathological process of cartilage degeneration through multiple signaling pathways, mainly mitogen-activated protein kinase, nuclear transcription factor kappa B, and Wnt-p-catenin signal transduction pathways. This review aimed at exploring the relationship between PTOA and inflammation-related cytokines by introducing the role of proinflammatory cytokines in chondrocyte destruction and extracellular matrix degradation.

Application of Arthroscopic Technology in the Treatment of Traumatic Sports Ankle Arthritis

Objective:To analyze and explore the clinical value of arthroscopy in traumatic sports ankle arthritis.Methods:The study period was from June 2016 to June 2020.A selected sample of 25 patients with traumatic sports ankle arthritis in Qingyang People's Hospital were treated.All patients underwent arthroscopy and the specific treatment effects were analyzed.Results:Comparing the preoperative and postoperative ankle-hindfoot scores,the distance of talus advancement,modified Mcguire's ankle scoring system,and visual analog scale(VAS)pain scores,the postoperative results were significantly better than those of the preoperative(P<0.05).Conclusion:Arthroscopy in traumatic sports ankle arthritis has a significant effect,with minor trauma and rapid postoperative recovery which improves various discomfort symptoms.It is worthy of promotion and application.

Clinical effect of sodium hyaluronate joint cavity filling combined with exercise therapy on patients with post-traumatic knee arthritis

Objective:To research the sodium hyaluronate joint cavity filling combined with exercise therapy on the indicator of pain,motor function,and levels of inflammatory factors in joint fluid in patients with post-traumatic knee arthritis.Method Totally 100 patients(Department of Orthopaedics,The second Affiliated Hospital to Liaoning University of Chinese Medicine,2013.10-2018.8)with post-traumatic knee arthritis were selected,then they were divided into observation group(n=50)and control group(n=50).The control group was given glucosamine sulfate and sodium hyaluronate joint cavity filling,the observation group was given leg press with visual feedback,they were treated 4 weeks.Assessing the pain degree through visual analog scale(VAS),hospital for special surgery knee score(HSS)as the indicator of motor function,inflammatory factor(TNF-α,IL-6,and IL-8)in the joint fluid.Results The score of VAS were lower than pretherapy(P<0.05),the degree of VAS of observation group were lower than control group(P<0.05).The score of HSS were higher than pretherapy(P<0.05),the degree of VAS of observation group were higher than control group(P<0.05).The inflammatory factor(TNF-α,IL-6,and CRP)in the joint fluid were lower than pretherapy(P<0.05),and the observation group were lower than control group(P<0.05).Conclusions Giving sodium hyaluronate joint cavity filling combined with exercise therapy can improve the function of joint.

The analysis of relevant risk factors of traumatic arthritis resulting from the surgery of acetabular fractures

Objective To explore the relevant risk factors of tramatic arthritis resulting from the surgery of acetabular fractures. Methods From January 2000 to January 2009,88 patients aged from 20 to 60 years old with acetabular fractures

How to establish an expected animal model of post-traumatic osteoarthritis?

Background：Animal models of osteoarthritis（OA）,including post-traumatic osteoarthritis and spontaneous osteoarthritis,have been established in many ways.In recent years,there have been many reports in various foreign academic journals,but animal models of post-traumatic osteoarthritis（distinct from spontaneous osteoarthritis） have rarely been established or summarized in these reports.Animal models of post-traumatic osteoarthritis show different characteristics depending on the animal species and modeling methods used,which is why we have written this article.Objective：To summarize the research progress and research status of animal models of post-traumatic osteoarthritis.Methods：A retrospective review of the animal model of post-traumatic osteoarthritis（OA） was conducted on the basis of reports retrieved from the PubMed database with the keywords for searching ＂animal model,post-traumatic osteoarthritis（PTOA）＂ from October 2006 to October 2016 and confided English language.A total of 80 academic articles on the study of animal models of traumatic osteoarthritis were retrieved,and 34 of them were included in this literature review after reading the free fulltext of them.Results：Different PTOA models based on different modeling methods and different animal species had their own characteristics.Different modeling methods should be selected according to different modeling animals.Conclusions：Considering the project funds,experimental objectives and technical conditions,appropriate experimental animal and modeling method should be selected based on synthetic considerations to obtain an appropriate PTOA model and ideal experimental results.

Bisphosphonate rescue post-traumatic osteoarthritis by promoting the calcium signaling in chondrocytes

Introduction Post-traumatic osteoarthritis(PTOA)is a long-term adverse consequence of joint trauma,e.g.,meniscus or ligament tears,which are among the most common injuries for young adults with excessive physical activities,such as athletes and military employees.Currently,few preventive treatments exist for PTOA,with typical outcomes being gradual cartilage degeneration and eventual loss of joint function.Apoptosis and altered etabolism of chondrocytes,the sole cell type in cartilage,may be responsible for the development of PTOA in a subset of patients without traumatic cartilage destruction but with persistent altered joint loading post-trauma,which is the focus of this study.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Within minutes of TBI,a neuroinflammatory response is triggered,driven by intricate molecular and cellular inflammatory processes.

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.

Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Distraction arthroplasty in osteoarthritis of the foot and ankle

Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of Rheumatoid Arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.