BACKGROUND:Spinal cord injury is a neurological disorder caused by traumatic or non-traumatic events,often leading to severe functional impairment below the injured segment.In recent years,neural stem cell transplantation has been considered to have significant therapeutic potential in regulating the inflammatory response after spinal cord injury,inhibiting excessive proliferation of glial scars,and promoting nerve regeneration. OBJECTIVE:To review and discuss the potential mechanism of action of acupuncture and neural stem cell transplantation therapy in inhibiting spinal cord injury-induced secondary injury,and to delve into the scientific basis for its treatment of spinal cord injury. METHODS:PubMed,Elsevier,WanFang,and CNKI databases were searched using"spinal cord injury,acupuncture,neural stem cells,SDF-1α/CXCR4 axis"as Chinese and English search terms.Totally 96 articles were finally included.The research findings of acupuncture combined with neural stem cells in the treatment of spinal cord injury were summarized and analyzed,and the mechanism of this combination therapy in the treatment of secondary injury after spinal cord injury was summarized. RESULTS AND CONCLUSION:(1)The stromal-derived factor 1α(SDF-1α)/chemokine receptor 4(CXCR4)axis plays a crucial role in neural stem cell transplantation for spinal cord injury.This signaling mechanism not only affects neural stem cell migration,proliferation,and differentiation,but is also a key factor in determining the efficiency of stem cell homing to the injury site.Therefore,the regulation of targeting this axis is of great significance in enhancing the therapeutic effect of spinal cord injury.(2)Acupuncture,as a traditional Chinese medicine therapy,shows unique advantages in the regulation of secondary injury in spinal cord injury.It can effectively reduce secondary injury after spinal cord injury by regulating inflammatory response,inhibiting apoptosis,improving microcirculation,reducing glial scar formation,and counteracting oxidative stress.(3)Acupuncture was also able to influence the expression and function of the SDF-1α/CXCR4 axis,thereby enhancing the homing and survival ability of neural stem cells and promoting nerve regeneration and functional recovery.(4)The therapy combining acupuncture and stem cell transplantation is an innovative treatment strategy for spinal cord injury and suitable for repairing neural circuits.It combines the wisdom of traditional Chinese medicine with the advantages of modern biotechnology,providing a new treatment option for spinal cord injury patients.However,this combination therapy is still in the research and exploration stage,and its long-term efficacy and safety need to be further verified.(5)Taken together,acupuncture and neural stem cell transplantation for the treatment of spinal cord injury has great potential for clinical application,but in-depth research and optimization of treatment options are still needed.In the future,we look forward to further revealing the efficacy mechanism and optimal indications of this therapy through more clinical trials and mechanism studies,so as to bring better hope of recovery and more efficient therapeutic effects to spinal cord injury patients.

BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of"spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target"in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while the drugs insulin-like growth factor 1 and eladavone,Chinese medicine ginseng saponin,acupuncture,and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy.(4)The related regulators of cellular autophagy are interconnected,and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy.(5)Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models,but there are no autophagy-related drugs used in the clinical practice,and their safety and efficacy need to be further investigated in the clinical field.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

OBJECTIVE To investigate the mechanism of action of Chaihu Shugan San(CSS)and its absorbed components,Meranzin hydrate(MH)and ferulic acid(FA),on atherosclerosis(AS)and depression.METHODS An AS combined with depres-sion model was established in ApoE-/-mice,which were randomly divided into the blank group,model group,CSS group,MH group,and FA group.AS progression was evaluated through lipid profile analysis(TC,TG,LDL-C,HDL-C),aortic plaque analysis(Oil Red O staining),and cardiac function assessment.Behavioral tests,including the open field test,light/dark box test,tail suspension test,and forced swim test,were conducted to evaluate depressive-like behaviors.Hippocampal neuronal morphology changes were ob-served through Golgi staining.Serum inflammatory cytokines(TNF-α,IL-1β,IL-6),neurotransmitters(5-HT,BDNF),and vas-cular adhesion molecules(VCAM-1)were measured.16S rRNA sequencing was used to analyze the gut microbiome composition.RE-SULTS Compared to the model group,the CSS,MH,and FA treatment groups showed improvements in several areas.First,signifi-cant reduction in AS lesions,lower blood lipid levels,and enhanced cardiovascular function were observed(P＜0.01,P＜0.001).Sec-ond,depressive-like behaviors were improved,with stronger activity and less immobility time.Damage to neuronal dendritic spines was also repaired(P＜0.05,P＜0.01,P＜0.001).Additionally,serum levels of inflammatory cytokines,neurotransmitters,and vascu-lar adhesion molecules were reversed(P＜0.05,P＜0.01,P＜0.001).Finally,gut microbiome α and β diversity were regulated,and beneficial bacteria abundance was increased.CONCLUSION CSS exhibits the best effects in treating both AS and depression.The two absorption components,MH and FA,together contribute to the anti-AS and anti-depression effects.At the same concentration,MH shows better anti-AS and anti-depression effects than FA.

OBJECTIVE To investigate the mechanism of action of Chaihu Shugan San(CSS)and its absorbed components,Meranzin hydrate(MH)and ferulic acid(FA),on atherosclerosis(AS)and depression.METHODS An AS combined with depres-sion model was established in ApoE-/-mice,which were randomly divided into the blank group,model group,CSS group,MH group,and FA group.AS progression was evaluated through lipid profile analysis(TC,TG,LDL-C,HDL-C),aortic plaque analysis(Oil Red O staining),and cardiac function assessment.Behavioral tests,including the open field test,light/dark box test,tail suspension test,and forced swim test,were conducted to evaluate depressive-like behaviors.Hippocampal neuronal morphology changes were ob-served through Golgi staining.Serum inflammatory cytokines(TNF-α,IL-1β,IL-6),neurotransmitters(5-HT,BDNF),and vas-cular adhesion molecules(VCAM-1)were measured.16S rRNA sequencing was used to analyze the gut microbiome composition.RE-SULTS Compared to the model group,the CSS,MH,and FA treatment groups showed improvements in several areas.First,signifi-cant reduction in AS lesions,lower blood lipid levels,and enhanced cardiovascular function were observed(P＜0.01,P＜0.001).Sec-ond,depressive-like behaviors were improved,with stronger activity and less immobility time.Damage to neuronal dendritic spines was also repaired(P＜0.05,P＜0.01,P＜0.001).Additionally,serum levels of inflammatory cytokines,neurotransmitters,and vascu-lar adhesion molecules were reversed(P＜0.05,P＜0.01,P＜0.001).Finally,gut microbiome α and β diversity were regulated,and beneficial bacteria abundance was increased.CONCLUSION CSS exhibits the best effects in treating both AS and depression.The two absorption components,MH and FA,together contribute to the anti-AS and anti-depression effects.At the same concentration,MH shows better anti-AS and anti-depression effects than FA.

BACKGROUND:Currently,spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service.The prevention,treatment,and rehabilitation of spinal cord injury have become an important topic in the field of medicine.Therefore,it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.OBJECTIVE:To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury,and based on the current status of clinical translation,to put forward a few thoughts and outlooks on their clinical use.METHODS:The first author searched CNKI and PubMed databases using"mesenchymal stem cells,exosomes,spinal cord injury,miRNA,pathophysiology,clinical translation,clinical trials,good manufacturing practice"as Chinese and English search terms.The types of literature included treatises and reviews,and the language types were English and Chinese.Finally,72 papers were screened and analyzed.RESULTS AND CONCLUSION:(1)This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs.A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins,repressing RAS homologous gene family member A,activating cyclophosphoadenosine effector-binding proteins,and signaling and transcriptional activation proteins 3,and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways.Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1,expression of interferon regulatory factor 5,Toll-like receptor 4/nuclear factor-kappa B pathway,and down-regulating related pro-inflammatory factors.Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2.(2)Further comparative analyses revealed that miR-216-5p,miR-145-5p,and miR-146b improved inflammatory responses by regulating related pathways.Combining these miRNAs may produce more significant effects;hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy.(3)There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury,which is related to the need to meet good manufacturing practices before they can be put into clinical use.Challenges such as the need for large-scale,high-volume cell production,the lack of an efficient and uniform method for isolating exosomes,and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry.(4)miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury,and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of"spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target"in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen species-responsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while the drugs insulin-like growth factor 1 and eladavone,Chinese medicine ginseng saponin,acupuncture,and hydrogel carrying basic fibroblast growth factor as inhibitors of cellular autophagy promote functional recovery after spinal cord injury by inhibiting excessive cellular autophagy.(4)The related regulators of cellular autophagy are interconnected,and the bi-directional effects of cellular autophagy on spinal cord injury make it necessary to further explore the dominant factors that regulate cellular autophagy.(5)Research on the use of autophagy as a therapeutic target for spinal cord injury is mostly carried out in animal models,but there are no autophagy-related drugs used in the clinical practice,and their safety and efficacy need to be further investigated in the clinical field.

BACKGROUND:Cell death and neuroinflammation are two important targets in the treatment of spinal cord injury.Pyroptosis is a programmed cell death closely related to neuroinflammation and targeted inhibition of pyroptosis after spinal cord injury is a promising therapeutic strategy. OBJECTIVE:To summarize the molecular mechanism,positive and negative regulatory factors and therapeutic strategies of pyroptosis in spinal cord injury. METHODS:The search terms were"spinal cord injury,pyroptosis,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),Caspase,Gasdermin D(GSDMD),IL-1β,IL-18"and 93 English literatures included in PubMed and Web of Science were finally selected for review. RESULTS AND CONCLUSION:As a newly discovered programmed cell death,pyroptosis has been shown to play an important role in the secondary injury stage after spinal cord injury.Among the regulatory factors of pyroptosis after spinal cord injury,CD73,NRF2,GDF-11,dopamine,FANCC and miR-423-5P could inhibit pyroptosis,while TLR4 and Aopps could promote pyroptosis.In terms of treatment,the active ingredients of traditional Chinese medicine(paeonol,tripterine,betulinic acid,piperine,kaempferol,and camptothecin),exosomes of various cell origins,and some drugs(metformin,topotecan,lithium,zinc,and carbon monoxide-releasing molecule 3)can effectively inhibit pyroptosis and reduce secondary spinal cord injury,but the toxicity and specific dose of these drugs need to be further studied.The specific molecular mechanism by which pyroptosis aggravates spinal cord injury is still poorly understood.The role of non-classical pathways and other inflammasomes is worth further exploration.At present,the research on pyroptosis after spinal cord injury only stays at the animal experiment stage.There are no related clinical studies and no approved targeted therapeutic drugs.(6)The application of pyroptosis after spinal cord injury has great potential,and its specific regulatory mechanism should be further studied in the future to provide a new target for the treatment of spinal cord injury.