This study draws on the classic theories and research achievements of university teacher development,and from the perspective of role conflict in social psychology,proposes policy recommendations for the development o...This study draws on the classic theories and research achievements of university teacher development,and from the perspective of role conflict in social psychology,proposes policy recommendations for the development of clinical teachers in medical colleges,including following different stages of teacher development and designing teaching development strategies at different levels;designing the content and form of teaching development activities to meet the temporal and spatial needs of clinical teachers;and building an academic community for clinical teachers to promote the creation of teaching development behaviors.展开更多
Taking role conflict as the starting point,this article examines and reflects on the development of clinical teachers.In the process of the occurrence,development,and resolution of role conflicts among clinical teache...Taking role conflict as the starting point,this article examines and reflects on the development of clinical teachers.In the process of the occurrence,development,and resolution of role conflicts among clinical teachers,there are many hidden issues related to the development of clinical teachers.The development of clinical teacher teaching and role conflict management contain similar educational philosophies and practical issues.This study draws on classic theories and research achievements in the development of university teachers and conducts theoretical analysis and practical reflection on the development of clinical teachers in medical colleges from the perspective of role conflict in social psychology.Policy recommendations are proposed,including strengthening the construction of teaching systems at the hospital organizational environment level,enhancing the role identity and teacher beliefs of clinical teachers,promoting their teaching development and academic learning,and ensuring their normal teaching investment;promoting leadership support at the level of interpersonal interaction and leveraging the role of colleague support in alleviating role conflicts;enhancing individual teacher beliefs,teacher role learning,and role skills.展开更多
Many studies have been done about the treatment of KCOT, but the recurrence rate still remains high despite the combination of surgical techniques used, associated with or without the use chemical solutions such as Ca...Many studies have been done about the treatment of KCOT, but the recurrence rate still remains high despite the combination of surgical techniques used, associated with or without the use chemical solutions such as Carnoy’s solution or Cryosurgery. Currently, there is no consensus concerning the therapeutic choice for the KCOT. The purpose of this study was to evaluate the different treatment methods used for the management of KCOT in the Second Affiliated Hospital of Jiamusi University and the results obtained from those treatment methods. Settings and Design: Clinical study was done at the Second Affiliated Hospital of Jiamusi University. Materials and Methods: Analytical retrospective review of 63 cases treated surgically from 2009 to 2015 at the Maxillofacial and Oral Surgery Department of the Second Affiliated Hospital of Jiamusi University. All cases diagnosed as KCOT and registered in the archives were used. The level of statistical significance was set at P < 0.05. Results: Of the 63 cases, 55.56% were male and 44.44% female. The sex ratio was 1.25 in favor of male and the average age was 42 years. 81% of the lesions were located in the mandible. Of 40 cases treated by enucleation with peripheral ostectomy, curettage and electric cauterization with application of 2% iodine tincture, no recurrence was found. Of 20 cases treated by the same surgical method but without the application of 2% iodine tincture, recurrence was found in 3 cases (4.76%). 3 cases treated by resection had no recurrence. Significant relation between recurrence and type of treatment was found (P < 0.05). Conclusion: In our series, those cases that were treated by combination of surgical methods used with 2% iodine tincture showed an “improvement” in the reduction of recurrence, suggesting a future question to be examined in experimental study is to test the effectiveness of 2% iodine tincture.展开更多
The hospital medical crisis management is the strategy adopted by hospitals for medical crisis.It aims to minimize the loss brought about by medical crisis to the hospital through management.By using 4R theory of cris...The hospital medical crisis management is the strategy adopted by hospitals for medical crisis.It aims to minimize the loss brought about by medical crisis to the hospital through management.By using 4R theory of crisis management and taking the incident of"sky-high medical expenses"happened in Second Affiliated Hospital of Harbin Medical University as an example,we study how to improve and perfect the medical crisis management strategy of hospitals in our country.As a result,we think hospitals can improve the crisis management strategy from four aspects of curtailment,preparation,reaction and resilience,so as to solve this issue appropriately,protect the legitimate rights and interests of patients to the greatest extent and promote the sustainable development of the hospital.展开更多
Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses ...Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses the law of large numbers and the central limit theorem to model to carry out the case study of FAHSYSU Simulation T,and takes measures of offsetting adverse selections to increase booking efficiency.The paper also analyzes how to apply the ancient Chinese theory that man is an integral part of nature to wipe out‘the market for lemons’.展开更多
Objective:This article aims to deeply analyze the feedback on teacher training in an affiliated hospital,so as to clarify the current needs and situation of teacher training and provide a scientific basis for further ...Objective:This article aims to deeply analyze the feedback on teacher training in an affiliated hospital,so as to clarify the current needs and situation of teacher training and provide a scientific basis for further optimizing the teacher training system.Methods:The current situation and needs of teacher training in the affiliated hospital were collected by designing and distributing Tomato Form questionnaires on the DingTalk platform.The questionnaire adopted a percent-point system,all of which were indeterminate multiple-choice questions.Results:The average age of the clinical teachers participating in the survey was 40.44±7.85 years old,with an average teaching length of 4–10 years.The results showed that 60.20%of teachers think that the amount of teacher training in an affiliated hospital is sufficient;91.10%of teachers think that the factors affecting training conflict with working hours;97.96%of teachers believe that the training time has an impact on the training effect;81.63%of teachers prefer online training;51.53%of teachers tend to arrange training time on working days;33.16%of teachers tend to train once a month;17.78%of teachers prefer to receive training on clinical theoretical courses and practical teaching norms and skills content.Conclusion:Based on the above survey results,we propose to build a comprehensive management mechanism for teacher training,including improving the access,training,and assessment mechanism for clinical teachers,and adjusting and optimizing the training program according to actual needs.At the same time,an effective communication platform should be built to promote the deep integration of teaching and practice and enhance social recognition,so as to comprehensively improve the teaching quality and medical service of the hospital.展开更多
Objective:To build a set of teaching staff construction and teaching quality monitoring system suitable for clinical practice teaching in affiliated hospitals of medical colleges,achieve continuous improvement of clin...Objective:To build a set of teaching staff construction and teaching quality monitoring system suitable for clinical practice teaching in affiliated hospitals of medical colleges,achieve continuous improvement of clinical education and teaching level,and ensure the quality of medical education talent cultivation.Methods:A modern clinical practice teaching quality monitoring system is constructed based on organizational structure construction,teaching staff system construction,quality control system construction,and information platform construction,combined with external audit and evaluation.Results:The hospital has established a Faculty Development and Teaching Evaluation Office specifically responsible for the cultivation of clinical teachers and the evaluation and supervision of teaching quality.A relatively complete teacher construction and teaching quality monitoring system has also been established for clinical practice teaching,thus achieving integration with the school’s quality control system in terms of management mechanism.At the same time,a set of teaching quality control mode based on the“Internet+”platform has been created by means of informatization.At present,this mode has won three national computer software copyrights and two second prizes for school-level teaching achievements.Conclusion:Through five years of practice,an“Internet+”teaching quality evaluation and monitoring system with the characteristics of teaching hospitals affiliated to local medical colleges has been established.In order to further standardize the training system of clinical teachers in affiliated hospitals,achieve self-monitoring and self-improvement in terms of teaching quality,and ensure the continuous improvement of clinical teaching quality,we will continue to promote the development of clinical teachers with quality and excellence,enrich the main team of quality monitoring,guide the transformation of the education mode from being“centered on teachers”to being“centered on students,”and realize the integration of internal and external quality monitoring systems.展开更多
Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a...Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various dise...Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impair...Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.展开更多
Debates regarding the specific effects of general anesthesia on developing brains have persisted for over 30 years.A consensus has been reached that prolonged,repeated,high-dose exposure to anesthetics is associated w...Debates regarding the specific effects of general anesthesia on developing brains have persisted for over 30 years.A consensus has been reached that prolonged,repeated,high-dose exposure to anesthetics is associated with a higher incidence of deficits in behavior and executive function,while single exposure has a relatively minor effect on long-term neurological function.In this review,we summarize the dose-dependent neuroprotective or neurotoxic effects of gamma-aminobutyric acid type A receptor agonists,a representative group of sedatives,on developing brains or central nervous system diseases.Most preclinical research indicates that anesthetics have neurotoxic effects on the developing brain through various signal pathways.However,recent studies on low-dose anesthetics suggest that they may promote neurodevelopment during this critical period.These findings are incomprehensible for the general“dose-effect”principles of pharmacological research,which has attracted researchers'interest and led to the following questions:What is the threshold for the dual effects exerted by anesthetics such as propofol and sevoflurane on the developing brain?To what extent can their protective effects be maximized?What are the underlying mechanisms involved in these effects?Consequently,this issue has essentially become a“mathematical problem.”After summarizing the dose-dependent effects of gamma-aminobutyric acid type A receptor agonist sedatives in both the developing brain and the brains of patients with central nervous system diseases,we believe that all such anesthetics exhibit specific threshold effects unique to each drug.These effects range from neuroprotection to neurotoxicity,depending on different brain functional states.However,the exact values of the specific thresholds for different drugs in various brain states,as well as the underlying mechanisms explaining why these thresholds exist,remain unclear.Further in-depth exploration of these issues could significantly enhance the therapeutic translational value of these anesthetics.展开更多
基金2023 Shaanxi Teacher Development Research Program“Research on the Construction and Improvement Path of a Teaching Engagement Model for Double-Qualified Teachers in Medical Colleges”(Project number:2023JSQ011)。
文摘This study draws on the classic theories and research achievements of university teacher development,and from the perspective of role conflict in social psychology,proposes policy recommendations for the development of clinical teachers in medical colleges,including following different stages of teacher development and designing teaching development strategies at different levels;designing the content and form of teaching development activities to meet the temporal and spatial needs of clinical teachers;and building an academic community for clinical teachers to promote the creation of teaching development behaviors.
基金2023 Shaanxi Teacher Development Research Program“Research on the Construction and Improvement Path of a Teaching Engagement Model for Double-Qualified Teachers in Medical Colleges”(Project number:2023JSQ011)。
文摘Taking role conflict as the starting point,this article examines and reflects on the development of clinical teachers.In the process of the occurrence,development,and resolution of role conflicts among clinical teachers,there are many hidden issues related to the development of clinical teachers.The development of clinical teacher teaching and role conflict management contain similar educational philosophies and practical issues.This study draws on classic theories and research achievements in the development of university teachers and conducts theoretical analysis and practical reflection on the development of clinical teachers in medical colleges from the perspective of role conflict in social psychology.Policy recommendations are proposed,including strengthening the construction of teaching systems at the hospital organizational environment level,enhancing the role identity and teacher beliefs of clinical teachers,promoting their teaching development and academic learning,and ensuring their normal teaching investment;promoting leadership support at the level of interpersonal interaction and leveraging the role of colleague support in alleviating role conflicts;enhancing individual teacher beliefs,teacher role learning,and role skills.
文摘Many studies have been done about the treatment of KCOT, but the recurrence rate still remains high despite the combination of surgical techniques used, associated with or without the use chemical solutions such as Carnoy’s solution or Cryosurgery. Currently, there is no consensus concerning the therapeutic choice for the KCOT. The purpose of this study was to evaluate the different treatment methods used for the management of KCOT in the Second Affiliated Hospital of Jiamusi University and the results obtained from those treatment methods. Settings and Design: Clinical study was done at the Second Affiliated Hospital of Jiamusi University. Materials and Methods: Analytical retrospective review of 63 cases treated surgically from 2009 to 2015 at the Maxillofacial and Oral Surgery Department of the Second Affiliated Hospital of Jiamusi University. All cases diagnosed as KCOT and registered in the archives were used. The level of statistical significance was set at P < 0.05. Results: Of the 63 cases, 55.56% were male and 44.44% female. The sex ratio was 1.25 in favor of male and the average age was 42 years. 81% of the lesions were located in the mandible. Of 40 cases treated by enucleation with peripheral ostectomy, curettage and electric cauterization with application of 2% iodine tincture, no recurrence was found. Of 20 cases treated by the same surgical method but without the application of 2% iodine tincture, recurrence was found in 3 cases (4.76%). 3 cases treated by resection had no recurrence. Significant relation between recurrence and type of treatment was found (P < 0.05). Conclusion: In our series, those cases that were treated by combination of surgical methods used with 2% iodine tincture showed an “improvement” in the reduction of recurrence, suggesting a future question to be examined in experimental study is to test the effectiveness of 2% iodine tincture.
基金This work was supported by supported by National Social Science fund Major Projects(Grand 18ZDA088)National Social Science Foundation Project(Grand 18BGL242).
文摘The hospital medical crisis management is the strategy adopted by hospitals for medical crisis.It aims to minimize the loss brought about by medical crisis to the hospital through management.By using 4R theory of crisis management and taking the incident of"sky-high medical expenses"happened in Second Affiliated Hospital of Harbin Medical University as an example,we study how to improve and perfect the medical crisis management strategy of hospitals in our country.As a result,we think hospitals can improve the crisis management strategy from four aspects of curtailment,preparation,reaction and resilience,so as to solve this issue appropriately,protect the legitimate rights and interests of patients to the greatest extent and promote the sustainable development of the hospital.
文摘Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses the law of large numbers and the central limit theorem to model to carry out the case study of FAHSYSU Simulation T,and takes measures of offsetting adverse selections to increase booking efficiency.The paper also analyzes how to apply the ancient Chinese theory that man is an integral part of nature to wipe out‘the market for lemons’.
基金2023 Shaanxi Teacher Development Research Program“Research on the Construction and Improvement Path of a Teaching Engagement Model for Double Qualified Teachers in Medical Colleges”(2023JSQ011)2022 Education and Teaching Reform Research Project of Xi’an Medical University“Construction and Practice of the Teaching Quality Assurance System in the Three-Level Teaching Base of General Practice Medicine under the Internet+Model”(2022JG-05)。
文摘Objective:This article aims to deeply analyze the feedback on teacher training in an affiliated hospital,so as to clarify the current needs and situation of teacher training and provide a scientific basis for further optimizing the teacher training system.Methods:The current situation and needs of teacher training in the affiliated hospital were collected by designing and distributing Tomato Form questionnaires on the DingTalk platform.The questionnaire adopted a percent-point system,all of which were indeterminate multiple-choice questions.Results:The average age of the clinical teachers participating in the survey was 40.44±7.85 years old,with an average teaching length of 4–10 years.The results showed that 60.20%of teachers think that the amount of teacher training in an affiliated hospital is sufficient;91.10%of teachers think that the factors affecting training conflict with working hours;97.96%of teachers believe that the training time has an impact on the training effect;81.63%of teachers prefer online training;51.53%of teachers tend to arrange training time on working days;33.16%of teachers tend to train once a month;17.78%of teachers prefer to receive training on clinical theoretical courses and practical teaching norms and skills content.Conclusion:Based on the above survey results,we propose to build a comprehensive management mechanism for teacher training,including improving the access,training,and assessment mechanism for clinical teachers,and adjusting and optimizing the training program according to actual needs.At the same time,an effective communication platform should be built to promote the deep integration of teaching and practice and enhance social recognition,so as to comprehensively improve the teaching quality and medical service of the hospital.
基金supported by the 2020 Education and Teaching Reform Research Project of Xi’an Medical University,“Construction of‘Double-Qualified’Teachers in Affiliated Hospitals Based on‘Online Learning Platform for Clinical Teachers’and Construction and Practice of Quality Assurance System”(Project Number:2020JG-02)the 2021 Shaanxi Undergraduate and Higher Continuing Education Teaching Reform Research Project of Shaanxi Provincial Department of Education,“Construction of Teaching Staff Based on‘Online Learning Platform for Clinical Teachers of the First Affiliated Hospital of Xi’an Medical University’and Construction and Practice of Quality Assurance System”(Project Number:21BZ066).
文摘Objective:To build a set of teaching staff construction and teaching quality monitoring system suitable for clinical practice teaching in affiliated hospitals of medical colleges,achieve continuous improvement of clinical education and teaching level,and ensure the quality of medical education talent cultivation.Methods:A modern clinical practice teaching quality monitoring system is constructed based on organizational structure construction,teaching staff system construction,quality control system construction,and information platform construction,combined with external audit and evaluation.Results:The hospital has established a Faculty Development and Teaching Evaluation Office specifically responsible for the cultivation of clinical teachers and the evaluation and supervision of teaching quality.A relatively complete teacher construction and teaching quality monitoring system has also been established for clinical practice teaching,thus achieving integration with the school’s quality control system in terms of management mechanism.At the same time,a set of teaching quality control mode based on the“Internet+”platform has been created by means of informatization.At present,this mode has won three national computer software copyrights and two second prizes for school-level teaching achievements.Conclusion:Through five years of practice,an“Internet+”teaching quality evaluation and monitoring system with the characteristics of teaching hospitals affiliated to local medical colleges has been established.In order to further standardize the training system of clinical teachers in affiliated hospitals,achieve self-monitoring and self-improvement in terms of teaching quality,and ensure the continuous improvement of clinical teaching quality,we will continue to promote the development of clinical teachers with quality and excellence,enrich the main team of quality monitoring,guide the transformation of the education mode from being“centered on teachers”to being“centered on students,”and realize the integration of internal and external quality monitoring systems.
基金supported by the National Natural Science Foundation of China,82471345(to LC)the Key Research and Development Program for Social Development by the Jiangsu Provincial Department of Science and Technology.No.BE2022668(to LC).
文摘Ischemic stroke is a major cause of neurological deficits and high disability rate.As the primary immune cells of the central nervous system,microglia play dual roles in neuroinflammation and tissue repair following a stroke.Their dynamic activation and polarization states are key factors that influence the disease process and treatment outcomes.This review article investigates the role of microglia in ischemic stroke and explores potential intervention strategies.Microglia exhibit a dynamic functional state,transitioning between pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.This duality is crucial in ischemic stroke,as it maintains a balance between neuroinflammation and tissue repair.Activated microglia contribute to neuroinflammation through cytokine release and disruption of the blood-brain barrier,while simultaneously promoting tissue repair through anti-inflammatory responses and regeneration.Key pathways influencing microglial activation include Toll-like receptor 4/nuclear factor kappa B,mitogen-activated protein kinases,Janus kinase/signal transducer and activator of transcription,and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways.These pathways are targets for various experimental therapies aimed at promoting M2 polarization and mitigating damage.Potential therapeutic agents include natural compounds found in drugs such as minocycline,as well as traditional Chinese medicines.Drugs that target these regulatory mechanisms,such as small molecule inhibitors and components of traditional Chinese medicines,along with emerging technologies such as single-cell RNA sequencing and spatial transcriptomics,offer new therapeutic strategies and clinical translational potential for ischemic stroke.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the National Natural Science Foundation of China,No.82001325Visiting Scholar Foundation of Shandong Province,No.20236-01(both to CS).
文摘Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金supported by the Natural Science Foundation of Chongqing,No.CSTB2023NSCQ-mSX0561(to WL).
文摘Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
基金supported by Applied Basic Research Foundation of Yunnan Province,Nos.202301AS070045,202101AY070001-115(to XY and BL)National Natural Science Foundation of China,No.81960242(to XY)。
文摘Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.
文摘Debates regarding the specific effects of general anesthesia on developing brains have persisted for over 30 years.A consensus has been reached that prolonged,repeated,high-dose exposure to anesthetics is associated with a higher incidence of deficits in behavior and executive function,while single exposure has a relatively minor effect on long-term neurological function.In this review,we summarize the dose-dependent neuroprotective or neurotoxic effects of gamma-aminobutyric acid type A receptor agonists,a representative group of sedatives,on developing brains or central nervous system diseases.Most preclinical research indicates that anesthetics have neurotoxic effects on the developing brain through various signal pathways.However,recent studies on low-dose anesthetics suggest that they may promote neurodevelopment during this critical period.These findings are incomprehensible for the general“dose-effect”principles of pharmacological research,which has attracted researchers'interest and led to the following questions:What is the threshold for the dual effects exerted by anesthetics such as propofol and sevoflurane on the developing brain?To what extent can their protective effects be maximized?What are the underlying mechanisms involved in these effects?Consequently,this issue has essentially become a“mathematical problem.”After summarizing the dose-dependent effects of gamma-aminobutyric acid type A receptor agonist sedatives in both the developing brain and the brains of patients with central nervous system diseases,we believe that all such anesthetics exhibit specific threshold effects unique to each drug.These effects range from neuroprotection to neurotoxicity,depending on different brain functional states.However,the exact values of the specific thresholds for different drugs in various brain states,as well as the underlying mechanisms explaining why these thresholds exist,remain unclear.Further in-depth exploration of these issues could significantly enhance the therapeutic translational value of these anesthetics.
