Objective: To evaluate the risk factors for hemoglobinuria and acute kidney injury(AKI) after percutaneous mechanical thrombectomy(MT) with or without catheter-directed thrombolysis(CDT) for iliofemoral deep vein thro...Objective: To evaluate the risk factors for hemoglobinuria and acute kidney injury(AKI) after percutaneous mechanical thrombectomy(MT) with or without catheter-directed thrombolysis(CDT) for iliofemoral deep vein thrombosis(IFDVT).Methods: Patients with IFDVT who had MT with the Angio Jet catheter(group A), MT plus CDT(group B), or CDT alone(group C) from January 2016 to March 2020 were retrospectively evaluated. Hemoglobinuria was monitored throughout the treatment course, and postoperative AKI was assessed by comparing the preoperative(baseline) and postoperative serum creatinine(sCr) levels from the electronic medical records of all patients. AKI was defined as an elevation in the sCr level exceeding 26.5 μmol/L within 72 h after the operation according to the Kidney Disease Improving Global Outcomes criteria.Results: A total of 493 consecutive patients with IFDVT were reviewed, of which 382(mean age, 56 ± 11 years;41% of them were females;97 in group A, 128 in group B, and 157 in group C) were finally analyzed. Macroscopic hemoglobinuria was evident in 44.89% of the patients of the MT groups(101/225, 39 in group A, and 62 in group B), with no significant difference between the groups(P = 0.219), but not in the patients in group C. None of the patients developed AKI(mean sCr difference-2.76 ± 13.80 μmol/L, range =-80.20 to 20.60 μmol/L) within 72h after surgery.Conclusions: Rheolytic MT is an independent risk factor for hemoglobinuria. A proper aspiration strategy, hydration, and alkalization following thrombectomy are particularly favorable for preventing AKI.展开更多
A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researche...A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.展开更多
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen...Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.展开更多
Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,...Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal regrowth.During development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).展开更多
Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control...Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.展开更多
Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain...Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking examples.Traumatic brain injury(TBI)is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death rate.TBI is characterized by two pathologically distinct but strictly consequential phases:a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue,which involves widespread cell death and tissue degeneration,followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient’s pre-existing health status.Secondary processes,including inflammatory phenomena,oxidative stress associated with metabolic,vascular,and neuro-modulatory deficits,are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities(Kaur and Sharma,2018).展开更多
Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site....Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.展开更多
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 ac...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.展开更多
What is spinal cord injury:Spinal cord injury(SCI)is the damage to the structure of the bundles of cells and nerves that communicate signals from the brain to the body and extremities.The pathology of SCI includes bot...What is spinal cord injury:Spinal cord injury(SCI)is the damage to the structure of the bundles of cells and nerves that communicate signals from the brain to the body and extremities.The pathology of SCI includes both primary and secondary injuries(Morales et al.,2016).Physical forces such as compression,shearing,contusion,and tearing are major causes of primary injury in SCI.There are two main processes in primary injury:acute and subacute.The acute phase includes traumatic disruption of axons and hemorrhage of the blood vessels around the spinal cord.Hemorrhagic injury to the vessels can lead to increased edema within the neural and cord tissues,susceptibility to infiltration by microglia and astrocytes,excitotoxicity,and demyelination.Similarly,disruption of the blood-spinal cord barrier results in the release of inflammatory cytokines from specific cells and vessels.展开更多
BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBO...BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.展开更多
Dear Editor,We present a case of acute Bacillus cereus(B.cereus)endophthalmitis in a patient with an intraocular perforation injury combined with occult intravitreal cilium implantation.B.cereus endophthalmitis is a s...Dear Editor,We present a case of acute Bacillus cereus(B.cereus)endophthalmitis in a patient with an intraocular perforation injury combined with occult intravitreal cilium implantation.B.cereus endophthalmitis is a severe intraocular infection commonly caused by post-traumatic injuries.It often leads to significant vision loss or even eye loss within 12-48h[1].The presence of an intraocular foreign body(IOFB)increases the risk of infection,while early surgical removal of IOFBs can prevent endophthalmitis,some IOFBs are difficult to detect preoperatively.The Medical Ethics Review Board of West China Hospital of Sichuan University waived application for a clinical study because this was a retrospective report of a single patient based on imaging and because no human experimentation was involved.The patient provided written informed consent to use the imaging data for publication.展开更多
Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting dist...Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.展开更多
Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been dif...Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been difficult because of the uncertainty of the consequences of doing so, and the absence of publications to help determine whether revaccination may be considered safe or not. Purpose: We present a case report of a 59-year-old Canadian man who developed severe acute kidney injury associated with moderate proteinuria following his first COVID-19 vaccine with the Moderna vaccine (an mRNA vaccine). He required haemodialysis for 2 weeks, which was initiated when his creatinine reached 1002 μmol/l. A kidney biopsy showed changes consistent with acute tubular necrosis. The patient was cautioned that repeat vaccination might result in further kidney injury which might be irreversible. However, he badly wanted to attempt a second COVID-19 vaccination, to facilitate a family vacation across several countries in Europe, at a time when travel restrictions were in place in many countries for persons who had not completed a course of vaccines. Method: Following deliberations, the patient chose to try a different type of Covid-19 vaccine. On this occasion, he was vaccinated with the Novavax vaccine (a subunit COVID-19 vaccine). Following this, close monitoring of his urine to detect proteinuria and blood testing for acute kidney injury were carried out on days 1, 3, 7, and 60 after vaccination. Furthermore, a year after his repeat vaccination, his kidney function and urinalysis were again assessed. Result and Conclusions: The patient did not develop acute kidney injury or worsening proteinuria following repeat vaccination. It remains unclear if acute kidney injury with proteinuria is caused by Covid-19 vaccination, or simply an incidental association. This case report suggests that it is may be reasonable for patients with acute kidney injury after COVID-19 vaccination to consider trying a different type of vaccine. In situations where a new virulent strain of virus emerges or in patients at risk of severe complication from infection, it may be reasonable to consider revaccination following appropriate counselling with close monitoring of renal function.展开更多
Background:Determining the incidence and prevalence of injury and illness in short-course triathletes would improve understanding of their etiologies and therefore assist in the development and implementation of preve...Background:Determining the incidence and prevalence of injury and illness in short-course triathletes would improve understanding of their etiologies and therefore assist in the development and implementation of prevention strategies.This study synthesizes the existing evidence on the incidence and prevalence of injury and illness and summarizes reported injury or illness etiology and risk factors affecting short-course triathletes.Methods:This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Studies reporting health problems(injury and illness)in triathletes(all sexes,ages,and experience levels)training and/or competing in short-course distances were included.Six electronic databases(Cochrane Central Register of Controlled Trials,MEDLINE,Embase,APA PsychINFO,Web of Science Core Collection,and SPORTDiscus)were searched.Risk of bias was independently assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale.Two authors independently completed data extraction.Results:The search yielded 7998 studies,with 42 studies eligible for inclusion.Twenty-three studies investigated injuries,24 studies investigated illnesses,and 5 studies investigated both injuries and illnesses.The injury incidence rate ranged 15.7-24.3 per 1000 athlete exposures,and the illness incidence rate ranged 1.8-13.1 per 1000 athlete days.Injury and illness prevalence ranged between 2%-15%and 6%-84%,respectively.Most injuries reported occurred during running(45%-92%),and the most frequently reported illnesses affected the gastrointestinal(7%-70%),cardiovascular(14%-59%),and respiratory systems(5%-60%).Conclusion:The most frequently reported health problems in short-course triathletes were:overuse and lower limb injuries associated with running;gastrointestinal illnesses and altered cardiac function,primarily attributable to environmental factors;and respiratory illness mostly caused by infection.展开更多
Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate w...Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.展开更多
Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect i...Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic inflammation.However,the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown.In this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal injection.We also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord injury.Our res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial cells.Furthermore,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway.These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.展开更多
There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult p...There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.展开更多
This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-ind...This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.展开更多
Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-...Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.展开更多
Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate...Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.展开更多
基金supported by the Medical and Health Science and Technology Development Plan of Shandong Province, China (Grant No.2017WS688)。
文摘Objective: To evaluate the risk factors for hemoglobinuria and acute kidney injury(AKI) after percutaneous mechanical thrombectomy(MT) with or without catheter-directed thrombolysis(CDT) for iliofemoral deep vein thrombosis(IFDVT).Methods: Patients with IFDVT who had MT with the Angio Jet catheter(group A), MT plus CDT(group B), or CDT alone(group C) from January 2016 to March 2020 were retrospectively evaluated. Hemoglobinuria was monitored throughout the treatment course, and postoperative AKI was assessed by comparing the preoperative(baseline) and postoperative serum creatinine(sCr) levels from the electronic medical records of all patients. AKI was defined as an elevation in the sCr level exceeding 26.5 μmol/L within 72 h after the operation according to the Kidney Disease Improving Global Outcomes criteria.Results: A total of 493 consecutive patients with IFDVT were reviewed, of which 382(mean age, 56 ± 11 years;41% of them were females;97 in group A, 128 in group B, and 157 in group C) were finally analyzed. Macroscopic hemoglobinuria was evident in 44.89% of the patients of the MT groups(101/225, 39 in group A, and 62 in group B), with no significant difference between the groups(P = 0.219), but not in the patients in group C. None of the patients developed AKI(mean sCr difference-2.76 ± 13.80 μmol/L, range =-80.20 to 20.60 μmol/L) within 72h after surgery.Conclusions: Rheolytic MT is an independent risk factor for hemoglobinuria. A proper aspiration strategy, hydration, and alkalization following thrombectomy are particularly favorable for preventing AKI.
基金supported by the Natural Science Foundation of Beijing,No.L222126(to LD)。
文摘A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX)and 81671189(to RX)。
文摘Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.
基金supported by grants from The University of Connecticut School of Medicine (StartUp Fund)the National Institutes of Health (NIH)(Grant R01-EY029 739)+1 种基金the Connecticut Institute for the Brain and Cognitive Sciences (Research Seed Grant)the BrightFocus Foundation (Grant G2017204)(all to EFT)
文摘Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal regrowth.During development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).
基金supported by the Veterans Administration (I01RX002264-01A2)(to PL)Wings For Life (WFL-US-10/21)(to CMF)。
文摘Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.
文摘Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking examples.Traumatic brain injury(TBI)is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death rate.TBI is characterized by two pathologically distinct but strictly consequential phases:a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue,which involves widespread cell death and tissue degeneration,followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient’s pre-existing health status.Secondary processes,including inflammatory phenomena,oxidative stress associated with metabolic,vascular,and neuro-modulatory deficits,are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities(Kaur and Sharma,2018).
基金supported by the patient organizations“Verticale”(to YNG and FEP).
文摘Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.
基金supported by Canadian Institutes for Health Research (CIHR)(to ADR and WW)Ontario Graduate Scholarship (to NOB)+2 种基金Alzheimer's Society of CanadaHeart and Stroke Foundation of Canada,CIHRthe Canadian Consortium for Neurodegeneration and Aging (CCNA)(to SNW)。
文摘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.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2022R1C1C1005410)(to GWL).
文摘What is spinal cord injury:Spinal cord injury(SCI)is the damage to the structure of the bundles of cells and nerves that communicate signals from the brain to the body and extremities.The pathology of SCI includes both primary and secondary injuries(Morales et al.,2016).Physical forces such as compression,shearing,contusion,and tearing are major causes of primary injury in SCI.There are two main processes in primary injury:acute and subacute.The acute phase includes traumatic disruption of axons and hemorrhage of the blood vessels around the spinal cord.Hemorrhagic injury to the vessels can lead to increased edema within the neural and cord tissues,susceptibility to infiltration by microglia and astrocytes,excitotoxicity,and demyelination.Similarly,disruption of the blood-spinal cord barrier results in the release of inflammatory cytokines from specific cells and vessels.
基金supported by military logistics scientific research project(AHJ16J004)。
文摘BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.
文摘Dear Editor,We present a case of acute Bacillus cereus(B.cereus)endophthalmitis in a patient with an intraocular perforation injury combined with occult intravitreal cilium implantation.B.cereus endophthalmitis is a severe intraocular infection commonly caused by post-traumatic injuries.It often leads to significant vision loss or even eye loss within 12-48h[1].The presence of an intraocular foreign body(IOFB)increases the risk of infection,while early surgical removal of IOFBs can prevent endophthalmitis,some IOFBs are difficult to detect preoperatively.The Medical Ethics Review Board of West China Hospital of Sichuan University waived application for a clinical study because this was a retrospective report of a single patient based on imaging and because no human experimentation was involved.The patient provided written informed consent to use the imaging data for publication.
基金supported by NIH grants NS084967,NS121037 (to AEK) and NS110609 (to COB)。
文摘Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.
文摘Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been difficult because of the uncertainty of the consequences of doing so, and the absence of publications to help determine whether revaccination may be considered safe or not. Purpose: We present a case report of a 59-year-old Canadian man who developed severe acute kidney injury associated with moderate proteinuria following his first COVID-19 vaccine with the Moderna vaccine (an mRNA vaccine). He required haemodialysis for 2 weeks, which was initiated when his creatinine reached 1002 μmol/l. A kidney biopsy showed changes consistent with acute tubular necrosis. The patient was cautioned that repeat vaccination might result in further kidney injury which might be irreversible. However, he badly wanted to attempt a second COVID-19 vaccination, to facilitate a family vacation across several countries in Europe, at a time when travel restrictions were in place in many countries for persons who had not completed a course of vaccines. Method: Following deliberations, the patient chose to try a different type of Covid-19 vaccine. On this occasion, he was vaccinated with the Novavax vaccine (a subunit COVID-19 vaccine). Following this, close monitoring of his urine to detect proteinuria and blood testing for acute kidney injury were carried out on days 1, 3, 7, and 60 after vaccination. Furthermore, a year after his repeat vaccination, his kidney function and urinalysis were again assessed. Result and Conclusions: The patient did not develop acute kidney injury or worsening proteinuria following repeat vaccination. It remains unclear if acute kidney injury with proteinuria is caused by Covid-19 vaccination, or simply an incidental association. This case report suggests that it is may be reasonable for patients with acute kidney injury after COVID-19 vaccination to consider trying a different type of vaccine. In situations where a new virulent strain of virus emerges or in patients at risk of severe complication from infection, it may be reasonable to consider revaccination following appropriate counselling with close monitoring of renal function.
文摘Background:Determining the incidence and prevalence of injury and illness in short-course triathletes would improve understanding of their etiologies and therefore assist in the development and implementation of prevention strategies.This study synthesizes the existing evidence on the incidence and prevalence of injury and illness and summarizes reported injury or illness etiology and risk factors affecting short-course triathletes.Methods:This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Studies reporting health problems(injury and illness)in triathletes(all sexes,ages,and experience levels)training and/or competing in short-course distances were included.Six electronic databases(Cochrane Central Register of Controlled Trials,MEDLINE,Embase,APA PsychINFO,Web of Science Core Collection,and SPORTDiscus)were searched.Risk of bias was independently assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale.Two authors independently completed data extraction.Results:The search yielded 7998 studies,with 42 studies eligible for inclusion.Twenty-three studies investigated injuries,24 studies investigated illnesses,and 5 studies investigated both injuries and illnesses.The injury incidence rate ranged 15.7-24.3 per 1000 athlete exposures,and the illness incidence rate ranged 1.8-13.1 per 1000 athlete days.Injury and illness prevalence ranged between 2%-15%and 6%-84%,respectively.Most injuries reported occurred during running(45%-92%),and the most frequently reported illnesses affected the gastrointestinal(7%-70%),cardiovascular(14%-59%),and respiratory systems(5%-60%).Conclusion:The most frequently reported health problems in short-course triathletes were:overuse and lower limb injuries associated with running;gastrointestinal illnesses and altered cardiac function,primarily attributable to environmental factors;and respiratory illness mostly caused by infection.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81970563)the Medical Health Science and Technology Project of Health Commission of Zhejiang Province(2019RC055).
文摘Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.
基金supported by the National Natural Science Foundation of China,Nos.81801226(to QK and XS)and 82101445(to XJ)。
文摘Spinal cord injury-induced motor dysfunction is associated with neuroinflammation.Studies have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic inflammation.However,the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown.In this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal injection.We also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord injury.Our res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial cells.Furthermore,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway.These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.
基金Division of Neurology,Cincinnati Children’s Hospital Medical Center(as a Medical Student Scholars Program award to ALM)。
文摘There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.
文摘This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.
基金supported by the Robert Campeau Family Foundation/Dr.C.H.Tator Chair in Brain and Spinal Cord Research(to MGF)。
文摘Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.
基金supported by the National Basic Research Program of China(2013CB127106)。
文摘Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.
