Network pharmacology investigation of the mechanism underlying the therapeutic action of Shikang granules in retinal ischemia-reperfusion injuries

Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway.

HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

Inhibition of the cGAS–STING pathway:contributing to the treatment of cerebral ischemia-reperfusion injury

The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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.

Bioprinted mesenchymal stem cell microfiber-derived extracellular vesicles alleviate unilateral renal ischemia-reperfusion injury and fibrosis by inhibiting tubular epithelial cells ferroptosis

Renal unilateral ischemia-reperfusion injury(UIRI)constitutes a significant global health challenge,with poor recovery leading to chronic kidney disease and subsequent renal fibrosis.Extracellular vesicles(EVs)present substantial potential benefits for renal diseases.However,the limited yield and efficacy of EVs produced through traditional methodologies(2D-EVs)severely restrict their widespread application.Moreover,the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored.In this study,we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology(3D-EVs)with a tail vein injection method,introducing a novel treatment strategy for UIRI.Our comparison of the biological functions of 2D-EVs and 3D-EVs,both in vitro and in vivo,reveals that 3D-EVs significantly outperform 2D-EVs.Specifically,in vitro,3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation(H/R)-induced injuries by reducing epithelial-mesenchymal transformation,extracellular matrix deposition,and ferroptosis.In vivo,3D-EVs exhibit enhanced therapeutic effects,as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys.We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells(TECs)ferroptosis through the modulation of SLC7A11 and GPX4 expression.Our findings suggest that bioprinted mesenchymal stem cells microfiberderived EVs significantly ameliorate renal UIRI,opening new avenues for effective and efficient EV-based therapies in UIRI treatment.

Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation

BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

The mechanisms that regulate neuronal pyroptosis in cerebral ischemia-reperfusion injury:current theories and recent advances

Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While these methods enhance tissue perfusion in the ischemic penumbra,they also trigger complex neurotoxic reactions,including apoptosis,acidosis,ion imbalance,oxidative stress,and pyroptosis,exacerbating cerebral ischemia-reperfusion injury(CIRI).Pyroptosis,a recently discovered form of programmed cell death driven by inflammation,plays a significant role in neuronal death during CIRI.This study reviews the regulatory mechanisms of pyroptosis in CIRI.

Ambulance Records as an Information Source to Document and Prevent Fall Injuries in Sweden

In Sweden, there has been only limited documentation for injuries requiring ambulance responses. The main objective of this study is, through the use of historic data, to assess the suitability of ambulance records to describe circumstances with fall injuries. Methods: The injury events data around patients were sourced from the ambulance data register. Descriptive statistics were used to describe injured patients based on age group, type of injury, place of injury, injury mechanism and consequence of an injury event. Two-group comparison was performed with Pearson’s chi-squared. Predictors of transport to hospital were identified using logistic regression analyses. Result: Ambulance provides unique data on all injury events, with direct implications for translational research, public policy and clinical practice (safety promotion). In 2002 ambulance attended 3964 injured people which represents 14% of ambulance attended workload in Värmland county, Sweden. The most common trauma location was the traffic area followed by residential area and nursing home. These three injury sites account for 2320 cases (61.6%). The most common cause of injury was falls (63.9%) followed by contact with another person (26.5%). Contact with another person is the most common site of injury in the traffic area (79.5%), and men aged 25-66 years are overrepresented. Conclusion: Logistic regression found that, age-group and place code were significant predictor for being attended by ambulance. Traffic, home and nursing homes were over-represented injury environments (61.6%) that require special attention. Most injury cases occur in the home and nursing homes among people over 67 years of age. Surprisingly, most of the injury events in the traffic environment are about hitting another person. Paramedics can provide rich and valuable data on injury events. Registration of such data is entirely possible and desirable, and can be used in preventive work.

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide

AIM:To investigate the antioxidant protective effect of Lycium barbarum glycopeptide(LbGP)pretreatment on retinal ischemia-reperfusion(I/R)injury(RIRI)in rats.METHODS:RIRI was induced in Sprague Dawley rats through anterior chamber perfusion,and pretreatment involved administering LbGP via gavage for 7d.After 24h of reperfusion,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(CREA)levels,retinal structure,expression of Caspase-3 and Caspase-8,superoxide dismutase(SOD)activity,and malondialdehyde(MDA)in the retina were measured.RESULTS:The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer(GCL)and nerve fiber layer(NFL)of rats subjected to RIRI,as shown by light microscopy and optical coherence tomography(OCT).Serum AST was higher in the model group than in the blank group(P=0.042),but no difference was found in ALT,AST,and CREA across the LbGP groups and model group.Caspase-3 expression was higher in the model group than in the blank group(P=0.006),but no difference was found among LbGP groups and the model group.Caspase-8 expression was higher in the model group than in the blank group(P=0.000),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).SOD activity was lower in the model group than in the blank group(P=0.001),and the decrease was slower in the 400 mg/kg LbGP group than in the model group(P=0.003).MDA content was higher in the model group than in the blank group(P=0.001),and lower in the 400 mg/kg LbGP group than in the model group(P=0.016).The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model.CONCLUSION:LbGP pretreatment exhibits dosedependent anti-inflammatory,and antioxidative effects by reducing Caspase-8 expression,preventing declines of SOD activity,and decreasing MDA content in the RIRI rat model.

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

The Role of Age as a Risk Factor for Pickleball-Related Injuries

Pickleball is a popular sport that includes players from many different demographics. The popularity has resulted in not only increases in participation but also in activity related injuries. The purpose of this study was to identify risk factors along with potential mechanisms for injuries related to pickleball and identify effective countermeasures. Methods included the identification of pickleball related injuries from a US National Emergency Room database (NEISS). A narrative section of the database was used to identify and categorize potential mechanisms of injury. Results indicated that the types and mechanisms of injury relate to three specific age groups: younger, middle age, and older players. Injuries to younger players under the age of 26 are likely the result of misuse of sport equipment. Middle aged players from 26 to 50 sustained injuries more related activity overuse. However, there were more concerns with players over 50 years of age with a great percentage resulting in cardia arrest or symptoms leading to more severe cardiovascular conditions. While pickleball activity should be encouraged as it is a beneficial form of physical activity, there should be specific age-group interventions to reduce injury. It should be highly recommended that doctors approve the activity for individual at risk for heart conditions and supervision for adults in that age group.

Epidemiology of work-related hand and wrist injuries in a referral center: A descriptive study

BACKGROUND Occupational hand and wrist injuries(OHWIs)account for 25%of work-related accidents in low-and middle-income countries.In Colombia,more than 500000 occupational accidents occurred in 2021,and although the rate declined to less than 5%in 2020 and 2021,at least one in four accidents involved a hand or wrist injury.AIM To describe the OHWIs in workers seen at the emergency room at a second-level hospital in Colombia.METHODS An observational study was performed using data from workers who experienced OHWIs and attended a second-level hospital,between June,2020 and May,2021.The overall frequency of OHWIs,as well as their distribution by sociodemo-graphic,clinical,and occupational variables,are described.Furthermore,association patterns between sex,anatomical area(fingers,hand,wrist),and type of job were analyzed by correspondence analysis(CA).RESULTS There were 2.101 workers treated for occupational accidents,423(20.3%)were cases of OHWIs,which mainly affected men(93.9%)with a median age of 31 years and who worked mainly in mining(75.9%).OHWIs were more common in the right upper extremity(55.3%)and comprised different types of injuries,such as contusion(42.1%),laceration(27.9%),fracture(18.7%),and crush injury(15.6%).They primarily affected the phalanges(95.2%),especially those of the first finger(25.7%).The CAs showed associations between the injured anatomical area and the worker’s job that differed in men and women(explained variance>90%).CONCLUSION One out of five workers who suffered occupational accidents in Cundinamarca,Columbia had an OHWI,affecting mainly males employed in mining.This occupational profile is likely to lead to prolonged rehabilitation,and permanent functional limitations.Our results might be useful for adjusting preventive measures in cluster risk groups.

Bicycle-related traumatic injuries: a retrospective study during COVID-19 pandemic

BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention.METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed.RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission.CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.

Risk factors for running-related injuries:An umbrella systematic review

Purpose:This umbrella systematic review(SR) of SRs and meta-analysis seeks to comprehensively synthesize existing literature to identify and consolidate the diverse range of risk factors contributing to running-related injuries(RRIs).Methods:Systematic searches were conducted on June 28,2023,across Web of Science,SPORTDiscus,Scopus,PubMed,and Cochrane Library.We included SRs,whether accompanied by meta-analyses or not,that focused on investigating risk factors for RRIs within observational studies.The methodological quality of the SRs was evaluated using the Assessing the Methodological Quality of Systematic Reviews Ⅱ.To assess the extent of overlap across reviews,the corrected covered area metric was calculated.Results:From 1509 records retrieved,13 SRs were included.The degree of overlap between SRs was low(4%),and quality varied from critically low(n=8) to low(n=5).Two hundred seven outcomes assessed in 148 primary studies were identified as being associated with the occurrence of RRIs.The effect sizes of the associations for which risk measures were reported(n=131) were classified as large(n=30,23%),medium(n=38,29%),small(n=48,37%) or no effect(n=15,11%).Running/training characteristics,health and lifestyle factors,along with morphological and biomechanical aspects,exhibit large effect sizes in increasing the risk for RRIs.Conclusion:Drawing from the outcomes of the low-quality SRs and associations with large effect sizes,our findings indicate that running/training characteristics and health and lifestyle factors,as well as morphological and biomechanical aspects,are all implicated in elevating the risk of RRIs,emphasizing the multifactorial basis of injury incidence in running.Given the low quality and heterogeneity of SR,individual findings warrant cautious interpretation.

Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.

Radiological findings of February 2023 twin earthquakes-related spine injuries

BACKGROUND The February 6,2023,twin earthquakes in Türkiye caused significant structural damage and a high number of injuries,particularly affecting the spine,which underscores the importance of understanding the distribution and nature of vertebral injuries in disaster victims.AIM To investigate the distribution of radiological findings of vertebral injuries in patients referred to a major tertiary center during the February 6,2023 twin earthquakes in Türkiye.METHODS With the approval of the institutional ethics committee,1216 examinations of 238 patients transferred from the region to a tertiary major hospital after the twin earthquakes of February 6,2023,were retrospectively analyzed for spine injuries.RESULTS Spine computed tomography(CT)scans were performed in 192 of 238 patients with a suspected spinal injury,42 of whom also had an magnetic resonance imaging(MRI).In 86 of 192 patients(44.79%;M:F=33:53)a spinal fracture was detected on CT and in 33 of 42 patients(78.57%;M:F=20:13)a spinal injury was found on MRI.Of the 86 patients in whom vertebral injury was detected,fractures were detected in the Denis-B group in 33,Denis-C in 4,Denis-D in 20 and Denis-E in 11 patients.Among the vertebral bodies:40"compression fractures",17"burst fractures",5"translational dislocation fractures",5"flexion-distraction fractures"and 58"prolonged forced fetal posture fractures"were detected.In addition,isolated transverse or spinous process fractures were found in eighteen vertebrae.CONCLUSION Our study highlights the prevalence and diverse spectrum of spinal injuries following the February 6,2023 twin earthquakes in Turkey underscoring the urgent need for effective management strategies in similar disaster scenarios,and emphasizing the"prolonged forced fetal posture"damage we encountered in earthquake victims who remained under the collapse for a long time.