Extracellular vesicles (EVs), defined as cell-secreted nanoscale vesicles that carry bioactive molecules, have emerged as a promising therapeutic strategy in tumor and tissue regeneration. Their potential in repairing intervertebral disc degeneration (IDD) through multidimensional regulatory mechanisms is a rapidly advancing field of research. This paper provided an overview of the mechanisms of EVs in IDD repair, thoroughly reviewed recent literature on EVs for IDD, domestically and internationally, and summarized their therapeutic mechanisms. In IDD repair, EVs could act through different mechanisms at the molecular, cellular, and tissue levels. At the molecular level, EVs could treat IDD by inhibiting inflammatory reactions, suppressing oxidative stress, and regulating the synthesis and decomposition of extracellular matrix. At the cellular level, EVs could treat IDD by inhibiting cellular pyroptosis, ferroptosis, and apoptosis and promoting cell proliferation and differentiation. At the tissue level, EVs could treat IDD by inhibiting neovascularization. EVs have a strong potential for clinical application in the treatment of IDD and deserve more profound study.
Extracellular Vesicles/physiology* ; Humans ; Intervertebral Disc Degeneration/therapy* ; Apoptosis ; Cell Proliferation ; Oxidative Stress ; Cell Differentiation ; Extracellular Matrix/metabolism* ; Animals ; Pyroptosis

OBJECTIVE: To summarize recent research progress in hydrogel-based growth factors for treatment of intervertebral disc degeneration (IDD). METHODS: The relevant literature on hydrogel-based growth factors for IDD treatment at home and abroad was extensively reviewed, and their advantages and therapeutic effects in repairing IDD were analyzed and summarized. RESULTS: Hydrogels exhibit high hydration, biocompatibility, and biodegradability, enabling targeted delivery and sustained release of growth factors such as growth differentiation factors and transforming growth factors. This facilitates enhanced efficacy in promoting cell proliferation, extracellular matrix synthesis, and reducing inflammatory responses. Consequently, hydrogels demonstrate broad application prospects in the repair of IDD. CONCLUSION Research on hydrogel-based growth factors for treating IDD demonstrates advantages such as avoiding disc damage caused by repeated injections and controlling growth factor release concentrations. However, drawbacks include the limited variety of loaded growth factors and the need to verify the long-term stability and biocompatibility of hydrogels. Therefore, further research is required on aspects such as the types of loaded growth factors and the long-term stability and biocompatibility of hydrogels to establish an experimental foundation for their clinical application.
Intervertebral Disc Degeneration/therapy* ; Hydrogels/chemistry* ; Humans ; Intercellular Signaling Peptides and Proteins/administration & dosage* ; Biocompatible Materials/chemistry* ; Animals ; Tissue Engineering/methods* ; Cell Proliferation/drug effects* ; Drug Delivery Systems

Objective:To explore the role of spinal Reelin protein (RELN) in neuropathic pain and its related mechanisms.Methods:A rat model of neuropathic pain induced by chronic constriction injury (CCI) was established using the sciatic nerve ligation method. The mechanical threshold and thermal threshold of the injured side and contralateral side in the sham-operation group and CCI group were compared. Western blot was used to detect the differences in the expressions of spinal RELN, calcium/calmodulin-dependent protein kinase Ⅱ (CAMKⅡ) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) proteins. On the 7th day after CCI modeling, the CCI model rats were further divided into three groups: CCI group (without any treatment), CCI+ RELN overexpression group (intrathecal injection of 15 μl of 5 μg/μl RELN overexpression plasmid, once a day for 2 consecutive days) and CCI+ PBS group (intrathecal injection of PBS). The mechanical threshold and thermal threshold among the three groups were compared, and Western blot was used again to detect the differences in the expressions of RELN, CaMKⅡ and p-ERK1/2 proteins in the three groups.Results:CCI successfully induced neuropathic pain in rats. On the 7th day after CCI, compared with the contralateral hind paw or the injured hind paw in the sham-operation group, the mechanical threshold and thermal threshold of the injured hind paw in the CCI group were significantly lower, with statistically significant differences (all P<0.001). Western blot results showed that compared with the sham-operation group, the protein expression of RELN in the spinal dorsal horn of the injured side in the CCI group was lower ( P=0.031), the protein expression of CAMKⅡ and the level of p-ERK1/2 were higher (all P<0.05), and there was no statistically significant difference in the level of ERK1/2 among the groups ( P>0.05). The thermal threshold and mechanical threshold of the injured side in the CCI+ RELN overexpression group were significantly higher than those in the CCI group and CCI+ PBS group (all P<0.05). Western blot results showed that 24 hours after the transfection of RELN overexpression plasmid, compared with the CCI+ PBS group, the protein expression of RELN in the CCI+ RELN overexpression group was significantly increased, with a statistically significant difference ( P<0.05), indicating that the transfection of RELN overexpression plasmid was successful. Compared with the CCI+ PBS group, the protein expression of CAMKⅡ and the phosphorylation level of ERK2 in the CCI+ RELN overexpression group were lower (all P<0.05), while there was no statistically significant difference in the phosphorylation level of ERK1 ( P>0.05). Conclusions:The overexpression of the RELN gene in the spinal cord weakens the maintenance of neuropathic pain by inhibiting the activation of the CAMKⅡ/ERK2 pathway, which suggests that RELN may become a new target for pain treatment.

Porcine intestinal organoids are 3D cultures derived from porcine stem cells or porcine intestinal crypts containing stem cells,which can self-renew and differentiate into tissues similar to those in vivo.Due to the high structural and physiological similarity between pigs and humans,porcine intestinal organoids can not only meet the needs of agricultural production and ecological environment research,but also serve as an in vitro model for human drug screening and toxicology studies.Compared with other in vitro models,porcine intestinal organoids have the advantages of being similar to in vivo tissues,stable phenotypes and genetic properties.Porcine intestinal organoids show great potential in simulating host-microbial interactions,drug screening and nutritional development studies,but their construction still lacks a fixed process,which affects experimental repeatability.In this review,we will review culture of porcine intestinal organoids,the exposure method of apical villi,the interactions between microorganisms and hosts,and the current challenges.

Intervertebral disc herniation is a highly prevalent orthopedic disorder,and intervertebral disc degeneration(IDD),the key pathological basis,is a complex pathological process characterized by progressive degradation of extracellular matrix,structural failure,and loss of biomechanical function,which not only shows higher prevalence in the population,but is also the primary cause of chronic low back pain and dysfunction worldwide,causing a huge socioeconomic burden.Although constructing IDD animal models is important for exploring the pathological mechanisms and promoting translational research of this disease,the etiology and pathophysiological mechanisms of IDD have not been fully elucidated.There are significant differences between humans and common laboratory animals in spinal anatomy,biomechanics,and degenerative course,coupled with the diversity and lack of unified standards of existing IDD animal models.This guide systematically reviews IDD animal models of rodents,non-human primates,as well as different species such as rabbits,goats/sheep,pigs,and dogs,focusing on the modeling principles of three main types of models:inducible models(such as annulus fibrosus/nucleus pulposus/endplate injury and mechanical injury)are suitable for simulating acute injury and rapid screening of therapies due to their high controllability and short cycle;spontaneous models can better simulate the age-related natural degeneration process in humans;genetically modified models provide powerful tools for analyzing specific molecular pathways.The guideline deeply analyzes the key technical points,reproducibility,and clinical relevance of these models.It also compares their advantages,limitations,and applicable research scenarios to guide researchers to conduct"scientific question-driven"precise model selection.Meanwhile,to improve the depth and comparability of research results,this guideline proposes a multidimensional endpoint evaluation system for IDD animal model experiments covering imaging,histology,biochemistry/molecular biology,biomechanics,and pain-related behavior,with recommended observation time windows.It also clarifies the"3Rs(replacement,reduction,and refinement)"ethical principles and animal welfare requirements throughout the experiment.In addition,the guideline outlines future research directions such as integrating single-cell omics,multiscale mechanical analysis,and strengthening pain-related phenotype assessment.This guideline aims to provide researchers with a systematic and standardized methodological framework for the rational selection and application of IDD animal models under specific scientific questions and resource constraints,in order to reduce inter-study heterogeneity,enhance the translation efficiency of preclinical findings,promote high-quality development in the field,and ultimately provide a solid scientific foundation for developing innovative therapies to delay or even reverse IDD.

Chronic pain following spinal cord injury refers to persistent or recurrent pain that occurs after spinal cord injury, which can be manifested as symptoms such as burning, stinging, and electric shock, seriously impairing the patients′ quality of life. Current conventional treatments for chronic pain after spinal cord injury include surgery, medication, and physical therapy. However, these treatments have limitations: surgery cannot fully repair nerve damage, medication has limited efficacy, and physical therapy often requires prolonged treatment with suboptimal outcomes. Spinal cord stimulation (SCS), as a neuromodulation technique, can relieve chronic pain in patients by stimulating spinal nerves by emitting weak current from electrodes placed around the spinal cord. SCS has been used to treat chronic pain after spinal cord injury, especially for refractory pain of the patients who fail to respond to conventional treatments, but its efficacy and exact mechanism remain to be further verified. To this end, this article reviewed the research progress of the efficacy and mechanism of SCS in the treatment of chronic pain after spinal cord injury so as to provide reference for its clinical treatment.

Spinal cord injury (SCI), as a serious traumatic disease of the central nervous system, often leads to irreversible damage to neurological function and has a high disability rate. Induced pluripotent stem cells (iPSCs) have the ability of self-renewal capacity and multilineage differentiation potential, and thus show broad application prospects and research value in the repair of SCI. iPSCs can replace damaged cells by directionally differentiating into neurons, oligodendrocytes, etc., secrete neurotrophic factors to optimize the microenvironment, promote myelin regeneration, and regulate immune responses. In recent years, research has concentrated on refining the directional differentiation protocol of iPSCs, improving survival rate and functional integration of transplanted cells, and actively exploring combined treatment strategies with biomaterial scaffolds, electrical stimulation, etc., to enhance the repair effect. Preclinical studies substantiate that iPSC transplantation can improve motor function, and early-phase clinical trials have also demonstrated its biological safety. Furthermore, iPSCs avoid ethical controversies and can be applied to disease modeling and mechanism research.

Aim To investigate the association of triglyceride-glucose(TyG)index with microvascular obstruction(MVO)after percutaneous coronary intervention(PCI)in patients with ST-segment elevated myocardial infarction(STEMI).Methods Individual patient-data were pooled from 310 patients with STEMI underwent emergency PCI in Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School from June 2018 to June 2021 for a prospective analysis.A week following the operation,cardiac magnetic resonance imaging was used to evaluate the MVO region and the patients were divided into two groups based on whether MVO occured after PCI:the MVO group(n=183)and the non-MVO group(n=127).The clinical data of the two groups were compared,and the linear relationship between TyG index and MVO was described using restricted cubic splines(RCS).Univariate and multivariate Logistic regression analysis were used to correct for confounding factors and identify independent risk factors for MVO occurrence.Results After adjustment for confounding factors,TyG index was an independent risk factor for MVO after emergency PCI in STEMI patients,and every 1-unit increased in TyG index,the risk of MVO increased by 1.24 times(OR=2.24,95％CI:1.07～4.71,P=0.033).The RCS curve analysis results showed that there was a linear re-lationship between the TyG index and the occurrence of MVO after emergency PCI(non-linear correlation test P=0.47).When the TyG index was greater than 9.5,the risk of MVO after emergency PCI significantly increased.Conclusion An increased TyG index is postively associated with the incidence of MVO in STEMI patients who have undergone PCI,and has clinical significantce for early prevention and risk stratification of MVO in STEMI patients.

Chronic pain following spinal cord injury refers to persistent or recurrent pain that occurs after spinal cord injury, which can be manifested as symptoms such as burning, stinging, and electric shock, seriously impairing the patients′ quality of life. Current conventional treatments for chronic pain after spinal cord injury include surgery, medication, and physical therapy. However, these treatments have limitations: surgery cannot fully repair nerve damage, medication has limited efficacy, and physical therapy often requires prolonged treatment with suboptimal outcomes. Spinal cord stimulation (SCS), as a neuromodulation technique, can relieve chronic pain in patients by stimulating spinal nerves by emitting weak current from electrodes placed around the spinal cord. SCS has been used to treat chronic pain after spinal cord injury, especially for refractory pain of the patients who fail to respond to conventional treatments, but its efficacy and exact mechanism remain to be further verified. To this end, this article reviewed the research progress of the efficacy and mechanism of SCS in the treatment of chronic pain after spinal cord injury so as to provide reference for its clinical treatment.

Intervertebral disc herniation is a highly prevalent orthopedic disorder,and intervertebral disc degeneration(IDD),the key pathological basis,is a complex pathological process characterized by progressive degradation of extracellular matrix,structural failure,and loss of biomechanical function,which not only shows higher prevalence in the population,but is also the primary cause of chronic low back pain and dysfunction worldwide,causing a huge socioeconomic burden.Although constructing IDD animal models is important for exploring the pathological mechanisms and promoting translational research of this disease,the etiology and pathophysiological mechanisms of IDD have not been fully elucidated.There are significant differences between humans and common laboratory animals in spinal anatomy,biomechanics,and degenerative course,coupled with the diversity and lack of unified standards of existing IDD animal models.This guide systematically reviews IDD animal models of rodents,non-human primates,as well as different species such as rabbits,goats/sheep,pigs,and dogs,focusing on the modeling principles of three main types of models:inducible models(such as annulus fibrosus/nucleus pulposus/endplate injury and mechanical injury)are suitable for simulating acute injury and rapid screening of therapies due to their high controllability and short cycle;spontaneous models can better simulate the age-related natural degeneration process in humans;genetically modified models provide powerful tools for analyzing specific molecular pathways.The guideline deeply analyzes the key technical points,reproducibility,and clinical relevance of these models.It also compares their advantages,limitations,and applicable research scenarios to guide researchers to conduct"scientific question-driven"precise model selection.Meanwhile,to improve the depth and comparability of research results,this guideline proposes a multidimensional endpoint evaluation system for IDD animal model experiments covering imaging,histology,biochemistry/molecular biology,biomechanics,and pain-related behavior,with recommended observation time windows.It also clarifies the"3Rs(replacement,reduction,and refinement)"ethical principles and animal welfare requirements throughout the experiment.In addition,the guideline outlines future research directions such as integrating single-cell omics,multiscale mechanical analysis,and strengthening pain-related phenotype assessment.This guideline aims to provide researchers with a systematic and standardized methodological framework for the rational selection and application of IDD animal models under specific scientific questions and resource constraints,in order to reduce inter-study heterogeneity,enhance the translation efficiency of preclinical findings,promote high-quality development in the field,and ultimately provide a solid scientific foundation for developing innovative therapies to delay or even reverse IDD.