Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations i...Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.展开更多
AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCT...AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.展开更多
Objective:To evaluate the nursing effects of auricular seed therapy combined with Chinese herbal poultice treatment for patients with lumbar disc herniation(LDH).Method:A total of 80 patients with LDH were randomly di...Objective:To evaluate the nursing effects of auricular seed therapy combined with Chinese herbal poultice treatment for patients with lumbar disc herniation(LDH).Method:A total of 80 patients with LDH were randomly divided into two groups.The combined group received auricular acupuncture with seed application combined with Chinese herbal poultice therapy,while the reference group received auricular acupuncture with seed application alone.The therapeutic outcomes of both groups were compared.Results:The combined intervention group demonstrated decreased sleep quality scores,reduced pain neurotransmitter levels,and improved lumbar spine function scores post-intervention,with significant intergroup differences(p<0.05).Conclusion:Auricular seed therapy combined with Chinese herbal poultice care effectively improves sleep quality and lumbar spine function while alleviating pain perception in patients with lumbar disc herniation,indicating superior therapeutic efficacy.展开更多
Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanism...Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc.By constructing a rat model of TMJ arthritis,we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant.By mimicking inflammatory conditions with interleukin-1 beta in vitro,we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment.In contrast,three-dimensional(3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils,inappropriate arrangement,and decreased Young’s modulus.Mechanistically,inflammation-related activation of the nuclear factor kappa-B(NF-κB)pathway occurs during the progression of TMJ arthritis.NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro,and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo.Therefore,the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs,offering a potential therapeutic target for disc displacement.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Large portions of the tunnel boring machine(TBM)construction cost are attributed to disc cutter consumption,and assessing the disc cutter's wear level can help determine the optimal time to replace the disc cutter...Large portions of the tunnel boring machine(TBM)construction cost are attributed to disc cutter consumption,and assessing the disc cutter's wear level can help determine the optimal time to replace the disc cutter.Therefore,the need to monitor disc cutter wear in real-time has emerged as a technical challenge for TBMs.In this study,real-time disc cutter wear monitoring is developed based on sound and vibration sensors.For this purpose,the microphone and accelerometer were used to record the sound and vibration signals of cutting three different types of rocks with varying abrasions on a laboratory scale.The relationship between disc cutter wear and the sound and vibration signal was determined by comparing the measurements of disc cutter wear with the signal plots for each sample.The features extracted from the signals showed that the sound and vibration signals are impacted by the progression of disc wear during the rock-cutting process.The signal features obtained from the rock-cutting operation were utilized to verify the machine learning techniques.The results showed that the multilayer perceptron(MLP),random subspace-based decision tree(RS-DT),DT,and random forest(RF)methods could predict the wear level of the disc cutter with an accuracy of 0.89,0.951,0.951,and 0.927,respectively.Based on the accuracy of the models and the confusion matrix,it was found that the RS-DT model has the best estimate for predicting the level of disc wear.This research has developed a method that can potentially determine when to replace a tool and assess disc wear in real-time.展开更多
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recen...Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.展开更多
Background: Lumbar disc herniation is a common injury among athletes, especially those who practice disciplines with repetitive flexion movements, twisting and axial loading on the spine, such as weightlifting, gymnas...Background: Lumbar disc herniation is a common injury among athletes, especially those who practice disciplines with repetitive flexion movements, twisting and axial loading on the spine, such as weightlifting, gymnastics, hockey and American football. In refractory cases to conservative treatment, microscopic discectomy or full endoscopic discectomy are used as surgical options to relieve pain and restore patient functionality. However, the ideal time for a return to sports activities remains a matter of debate due to variations in recovery times and risks of complications associated with each technique. Methods: A review was conducted, including articles published in the last 33 years (1991-2024), as it was the earliest date matching our search criteria. Clinical studies, systematic reviews, meta-analyses, and clinical guidelines were included. Results: The most common complications when returning to sport prematurely include recurrence of the hernia, persistent pain (VAS leg 7 or higher after surgery) and reduced physical performance. The return to full activity rate of patients who underwent microdiscectomy reaches up to 90%, while the endoscopic technique shows a success rate that reaches 99%. Return to play meantime was 5.19 months (range 1.00 - 8.7 months) and mean time of 4.6 months (range 2 - 8 months) with Microdiscectomy and full endoscopic discectomy respectively. Conclusions: There is no unanimous consensus on the exact timing of return to sport due to variability in recovery times and clinical outcomes. In both techniques, evidence highlights the need for a multidisciplinary approach that integrates surgeons, physical therapists and trainers to optimize recovery and ensure a safe return.展开更多
Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulp...Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.展开更多
Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-med...Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.展开更多
Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and in...Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.展开更多
Background: Surgical treatment of lumbar disc herniation is a widely debated topic, with several techniques available. Percutaneous endoscopic discectomy (PELD) has gained popularity due to its lower invasiveness comp...Background: Surgical treatment of lumbar disc herniation is a widely debated topic, with several techniques available. Percutaneous endoscopic discectomy (PELD) has gained popularity due to its lower invasiveness compared to conventional techniques such as microdiscectomy/open lumbar microdiscectomy (OLMD)/tubular microdiscectomy (TMD). However, evidence on the effectiveness, recovery time and complications of these techniques is not yet clearly established. This systematic review aims to compare the preoperative and postoperative outcomes of both techniques. Methods: A comprehensive search was performed in databases including PubMed and Cochrane, following strict inclusion and exclusion criteria. Comparative studies and narrative reviews on PELD and OLMD/TMD published between 2019 and 2024 were included. Key outcomes considered were pre- and postoperative Visual Analogue Scale (VAS), hospitalization time, time to return to work, and postoperative complications. Results: The reviewed studies indicated that PELD is associated with a greater reduction in postoperative pain compared to OLMD/TMD, with a significant decrease in VAS, according to the study by Priola et al. (2019). The hospital stay was also shorter for patients undergoing PELD, averaging 2 days compared to OLMD/TMD. Furthermore, PELD favored a faster return to work and had a lower rate of postoperative complications, such as dural tears and reoperations, compared to OLMD/TMD. Conclusions: PELD demonstrates clear advantages over OLMD/TMD in terms of pain reduction, shorter hospital stay, faster return to work, and fewer postoperative complications. However, the implementation of this technique requires a significant learning curve, suggesting that its effectiveness may vary depending on the surgeon’s experience. PELD should be considered a preferred option in the resection of lumbar disc herniations, especially in patients seeking a quick and less invasive recovery.展开更多
Pipeline Inspection Gauge(pig)is an important equipment for oil and gas pipelines during different stages of their operations to perform functions such as dewatering,cleaning,and inspection.Owing to the hyperelasticit...Pipeline Inspection Gauge(pig)is an important equipment for oil and gas pipelines during different stages of their operations to perform functions such as dewatering,cleaning,and inspection.Owing to the hyperelasticity,time and temperature-dependent material behaviour of the sealing disc attached on the pig,the contact between the pig and the pipeline expresses complex behaviour,leading to an uncertainty in the prediction of the pig's frictional force.Knowing the deformation of the sealing discs well is essential and can be highly meaningful for predicting the pig motion,as well as reducing the pigging risks.In this study,the geometrical deformation of the sealing discs with different sizes are investigated through experiments and numerical simulations.The effects of the four nondimensionalized parameters(interference,thickness per pipeline inner diameter,and clamping ratio)of the sealing discs on the deformation behaviour were observed and discussed,and an improved mathematical model for predicting the geometrical deformation of the sealing discs was proposed and verified.With the auxiliary angleαadded in the improved mathematical model,the relative error declines to 1.87%and 3.18%respectively for predicting deformation of the sealing discs in size of 2-inch and 40-inch pig.The results of this study can help better understand the frictional force of a pig with sealing discs,as well as its motion.展开更多
BACKGROUND Lumbar disc extrusion,a common spinal disorder,is particularly uncommon in its severely displaced form,especially in young patients.This condition can pose diagnostic challenges due to its nonspecific prese...BACKGROUND Lumbar disc extrusion,a common spinal disorder,is particularly uncommon in its severely displaced form,especially in young patients.This condition can pose diagnostic challenges due to its nonspecific presentation.CASE SUMMARY A 36-year-old male patient presented with persistent low back pain and radiating leg pain lasting half a month,which had worsened over the previous four days.Lumbar magnetic resonance imaging scans showed an abnormal signal within the vertebral canal at the L3 level,suggesting either a disc cyst or an epidural hematoma.Based on these findings,the patient was provisionally diagnosed with either condition.Surgical exploration was conducted,revealing an extruded lumbar disc,which was subsequently excised.Following surgery,the patient's symptoms completely resolved.CONCLUSION High-grade lumbar disc extrusion in young patients is rare but should be considered in sedentary,physically inactive individuals presenting with lumbocrural pain and abnormal magnetic resonance imaging findings.Early and accurate diagnosis is crucial to avoid misdiagnosis,and prompt open surgery may be necessary in severe cases to alleviate symptoms.The case highlights the impotance of a thorough diagnostic workup and timely surgical intervention in managing such rare but potentially severe spinal disorders.展开更多
The widespread adoption of tunnel boring machines(TBMs)has led to an increased focus on disc cutter wear,including both normal and abnormal types,for efficient and safe TBM excavation.However,abnormal wear has yet to ...The widespread adoption of tunnel boring machines(TBMs)has led to an increased focus on disc cutter wear,including both normal and abnormal types,for efficient and safe TBM excavation.However,abnormal wear has yet to be thoroughly investigated,primarily due to the complexity of considering mixed ground conditions and the imbalance in the number of instances between the two types of wear.This study developed a prediction model for abnormal TBM disc cutter wear,considering mixed ground conditions,by employing interpretable machine learning with data augmentation.An equivalent elastic modulus was used to consider the characteristics of mixed ground conditions,and wear data was obtained from 65 cutterhead intervention(CHI)reports covering both mixed ground and hard rock sections.With a balanced training dataset obtained by data augmentation,an extreme gradient boosting(XGB)model delivered acceptable results with an accuracy of 0.94,an F1-score of 0.808,and a recall of 0.8.In addition,the accuracy for each individual disc cutter exhibited low variability.When employing data augmentation,a significant improvement in recall was observed compared to when it was not used,although the difference in accuracy and F1-score was marginal.The subsequent model interpretation revealed the chamber pressure,cutter installation radius,and torque as significant contributors.Specifically,a threshold in chamber pressure was observed,which could induce abnormal wear.The study also explored how elevated values of these influential contributors correlate with abnormal wear.The proposed model offers a valuable tool for planning the replacement of abnormally worn disc cutters,enhancing the safety and efficiency of TBM operations.展开更多
Background:Renshen Guben oral liquid(RGSB)has the ability to consolidate constitution,restore vitality,and delay the ageing process and the onset of geriatric diseases.RGSB also has potential therapeutic effects on in...Background:Renshen Guben oral liquid(RGSB)has the ability to consolidate constitution,restore vitality,and delay the ageing process and the onset of geriatric diseases.RGSB also has potential therapeutic effects on intervertebral disc degeneration(IVDD).This study investigated the therapeutic effects of RGSB on IVDD and explored the underlying mechanisms.Methods:Single-cell sequencing and network pharmacology analyses were conducted in combination to determine the mechanisms of IVDD.Thirty-two C57BL/6J mice were randomly assigned to four groups:the sham operation group,IVDD group,Ibuprofen(IB)group,and RGSB group.All groups except for the sham operation group underwent needle puncture of the caudal IVDs.Behavioral tests,ELISA,PCR,TUNEL staining,and immunohistochemical staining were performed to investigate the therapeutic mechanisms associated with IVDD.Results:Bioinformatics analysis revealed that apoptosis is involved in the development of IVDD and that RSGB might alleviate IVDD by inhibiting apoptosis.After needle puncture,the mice exhibited from thermal allodynia,a decrease in disc height,an increase in the Pfirrmann grade,and destruction of IVDs.Surgery to induce IVDD increased the levels of Matrix Metalloproteinase-3(MMP3),Caspase-6,and Cyt-c in nucleus pulposus cells and the periphery;serum levels of interleukin-1β(IL‐1β)and TNF‐α;and the mRNA levels of IL-6,TNF-α,and IL-1β.Moreover,IVDD decreased the IL-10 mRNA level and the expression of Col-I and BCL2.RSGB reversed these changes.Conclusion:RSGB alleviated IVDD by relieving inflammation and apoptosis and alleviating neuroinflammation.展开更多
基金supported by the National Natural Science Foundation of China(32270887,82272507,32200654,82430079,and 82472519)the National Key Research and Development Program of China(2022YFA1103202)+7 种基金the Chongqing High-End Medical Talents for Middle-aged and Young(YXGD202408)the Army Scientific and Technological Innovation Talents Prioritized Suppor t Program(2023-124)the Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)the Postdoctoral Innovative Talent Support Program(BX20220397)the Open Project of State Key Laboratory of TraumaBurns and Combined Injury(SFLKF202201)the Project for Enhancing Innovation of Army Medical University(2023XJS39)the Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)。
文摘Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.
基金Central High-Level Traditional Chinese Medicine Hospital Project of Eye Hospital China Academy of Chinese Medical Science(No.GSP5-83,No.GSP4-02No.GSP5-06)+1 种基金Supported by National Natural Science Foundation of China(General ProgramNo.82474582).
文摘AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.
文摘Objective:To evaluate the nursing effects of auricular seed therapy combined with Chinese herbal poultice treatment for patients with lumbar disc herniation(LDH).Method:A total of 80 patients with LDH were randomly divided into two groups.The combined group received auricular acupuncture with seed application combined with Chinese herbal poultice therapy,while the reference group received auricular acupuncture with seed application alone.The therapeutic outcomes of both groups were compared.Results:The combined intervention group demonstrated decreased sleep quality scores,reduced pain neurotransmitter levels,and improved lumbar spine function scores post-intervention,with significant intergroup differences(p<0.05).Conclusion:Auricular seed therapy combined with Chinese herbal poultice care effectively improves sleep quality and lumbar spine function while alleviating pain perception in patients with lumbar disc herniation,indicating superior therapeutic efficacy.
基金supported by the National Natural Science Foundation of China Nos.82370983,81671015(X.W.),82230030(Y.L.),82101043(S.C.)and 82370922(Y.F.)Beijing International Science and Technology Cooperation Project No.Z221100002722003(Y.L.)+4 种基金Beijing Natural Science Foundation Nos.L234017,JL23002(Y.L.),No.7242282(S.C.)and 7232217(Y.G.)Clinical Medicine Plus X-Young Scholars Project of Peking University No.PKU2024LCXQ039(Y.L.)National Program for Multidisciplinary Cooperative Treatment on Major Diseases No.PKUSSNMP-202013(X.W.)Hygiene and Health Development Scientific Research Fostering Plan of Haidian District Beijing No.HP2023-12-509001(J.Z.)Young Clinical Research Fund of the Chinese Stomatological Association No.CSA-02022-03(J.Z.).
文摘Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc.By constructing a rat model of TMJ arthritis,we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant.By mimicking inflammatory conditions with interleukin-1 beta in vitro,we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment.In contrast,three-dimensional(3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils,inappropriate arrangement,and decreased Young’s modulus.Mechanistically,inflammation-related activation of the nuclear factor kappa-B(NF-κB)pathway occurs during the progression of TMJ arthritis.NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro,and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo.Therefore,the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs,offering a potential therapeutic target for disc displacement.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
文摘Large portions of the tunnel boring machine(TBM)construction cost are attributed to disc cutter consumption,and assessing the disc cutter's wear level can help determine the optimal time to replace the disc cutter.Therefore,the need to monitor disc cutter wear in real-time has emerged as a technical challenge for TBMs.In this study,real-time disc cutter wear monitoring is developed based on sound and vibration sensors.For this purpose,the microphone and accelerometer were used to record the sound and vibration signals of cutting three different types of rocks with varying abrasions on a laboratory scale.The relationship between disc cutter wear and the sound and vibration signal was determined by comparing the measurements of disc cutter wear with the signal plots for each sample.The features extracted from the signals showed that the sound and vibration signals are impacted by the progression of disc wear during the rock-cutting process.The signal features obtained from the rock-cutting operation were utilized to verify the machine learning techniques.The results showed that the multilayer perceptron(MLP),random subspace-based decision tree(RS-DT),DT,and random forest(RF)methods could predict the wear level of the disc cutter with an accuracy of 0.89,0.951,0.951,and 0.927,respectively.Based on the accuracy of the models and the confusion matrix,it was found that the RS-DT model has the best estimate for predicting the level of disc wear.This research has developed a method that can potentially determine when to replace a tool and assess disc wear in real-time.
基金supported by the Michael Michelson Gift FundNIA grants R01AG073349 (M.V.R.), R01AG044034 (R.F.L.), and R01AG078609 (J.C.)
文摘Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.
文摘Background: Lumbar disc herniation is a common injury among athletes, especially those who practice disciplines with repetitive flexion movements, twisting and axial loading on the spine, such as weightlifting, gymnastics, hockey and American football. In refractory cases to conservative treatment, microscopic discectomy or full endoscopic discectomy are used as surgical options to relieve pain and restore patient functionality. However, the ideal time for a return to sports activities remains a matter of debate due to variations in recovery times and risks of complications associated with each technique. Methods: A review was conducted, including articles published in the last 33 years (1991-2024), as it was the earliest date matching our search criteria. Clinical studies, systematic reviews, meta-analyses, and clinical guidelines were included. Results: The most common complications when returning to sport prematurely include recurrence of the hernia, persistent pain (VAS leg 7 or higher after surgery) and reduced physical performance. The return to full activity rate of patients who underwent microdiscectomy reaches up to 90%, while the endoscopic technique shows a success rate that reaches 99%. Return to play meantime was 5.19 months (range 1.00 - 8.7 months) and mean time of 4.6 months (range 2 - 8 months) with Microdiscectomy and full endoscopic discectomy respectively. Conclusions: There is no unanimous consensus on the exact timing of return to sport due to variability in recovery times and clinical outcomes. In both techniques, evidence highlights the need for a multidisciplinary approach that integrates surgeons, physical therapists and trainers to optimize recovery and ensure a safe return.
基金supported by National Natural Science Foundation of China(82272549,82472505,and 82472498)National key Research and Development plan,Ministry of Science and Technology of the People’s Republic of China(2022YFC2407203)+2 种基金the Young Health Talents of Shanghai Municipal Health Commission,China(2022YQ011)China Medical Education Association(3030537245)The Youth Talent Project of Huashan Hospital(30302164006).
文摘Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.
基金supported by the National Natural Science Foundation of China (NSFC) (No.82172497)
文摘Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.
基金Supported by 2024 Yeungnam University Grant,No.224A480005.
文摘Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.
文摘Background: Surgical treatment of lumbar disc herniation is a widely debated topic, with several techniques available. Percutaneous endoscopic discectomy (PELD) has gained popularity due to its lower invasiveness compared to conventional techniques such as microdiscectomy/open lumbar microdiscectomy (OLMD)/tubular microdiscectomy (TMD). However, evidence on the effectiveness, recovery time and complications of these techniques is not yet clearly established. This systematic review aims to compare the preoperative and postoperative outcomes of both techniques. Methods: A comprehensive search was performed in databases including PubMed and Cochrane, following strict inclusion and exclusion criteria. Comparative studies and narrative reviews on PELD and OLMD/TMD published between 2019 and 2024 were included. Key outcomes considered were pre- and postoperative Visual Analogue Scale (VAS), hospitalization time, time to return to work, and postoperative complications. Results: The reviewed studies indicated that PELD is associated with a greater reduction in postoperative pain compared to OLMD/TMD, with a significant decrease in VAS, according to the study by Priola et al. (2019). The hospital stay was also shorter for patients undergoing PELD, averaging 2 days compared to OLMD/TMD. Furthermore, PELD favored a faster return to work and had a lower rate of postoperative complications, such as dural tears and reoperations, compared to OLMD/TMD. Conclusions: PELD demonstrates clear advantages over OLMD/TMD in terms of pain reduction, shorter hospital stay, faster return to work, and fewer postoperative complications. However, the implementation of this technique requires a significant learning curve, suggesting that its effectiveness may vary depending on the surgeon’s experience. PELD should be considered a preferred option in the resection of lumbar disc herniations, especially in patients seeking a quick and less invasive recovery.
基金supported by Key Technologies Research and Development Program(Grant No.SQ2022YFC2806103)and the National Natural Science Foundation of China(Grant No.51509259).
文摘Pipeline Inspection Gauge(pig)is an important equipment for oil and gas pipelines during different stages of their operations to perform functions such as dewatering,cleaning,and inspection.Owing to the hyperelasticity,time and temperature-dependent material behaviour of the sealing disc attached on the pig,the contact between the pig and the pipeline expresses complex behaviour,leading to an uncertainty in the prediction of the pig's frictional force.Knowing the deformation of the sealing discs well is essential and can be highly meaningful for predicting the pig motion,as well as reducing the pigging risks.In this study,the geometrical deformation of the sealing discs with different sizes are investigated through experiments and numerical simulations.The effects of the four nondimensionalized parameters(interference,thickness per pipeline inner diameter,and clamping ratio)of the sealing discs on the deformation behaviour were observed and discussed,and an improved mathematical model for predicting the geometrical deformation of the sealing discs was proposed and verified.With the auxiliary angleαadded in the improved mathematical model,the relative error declines to 1.87%and 3.18%respectively for predicting deformation of the sealing discs in size of 2-inch and 40-inch pig.The results of this study can help better understand the frictional force of a pig with sealing discs,as well as its motion.
文摘BACKGROUND Lumbar disc extrusion,a common spinal disorder,is particularly uncommon in its severely displaced form,especially in young patients.This condition can pose diagnostic challenges due to its nonspecific presentation.CASE SUMMARY A 36-year-old male patient presented with persistent low back pain and radiating leg pain lasting half a month,which had worsened over the previous four days.Lumbar magnetic resonance imaging scans showed an abnormal signal within the vertebral canal at the L3 level,suggesting either a disc cyst or an epidural hematoma.Based on these findings,the patient was provisionally diagnosed with either condition.Surgical exploration was conducted,revealing an extruded lumbar disc,which was subsequently excised.Following surgery,the patient's symptoms completely resolved.CONCLUSION High-grade lumbar disc extrusion in young patients is rare but should be considered in sedentary,physically inactive individuals presenting with lumbocrural pain and abnormal magnetic resonance imaging findings.Early and accurate diagnosis is crucial to avoid misdiagnosis,and prompt open surgery may be necessary in severe cases to alleviate symptoms.The case highlights the impotance of a thorough diagnostic workup and timely surgical intervention in managing such rare but potentially severe spinal disorders.
基金support of the“National R&D Project for Smart Construction Technology (Grant No.RS-2020-KA157074)”funded by the Korea Agency for Infrastructure Technology Advancement under the Ministry of Land,Infrastructure and Transport,and managed by the Korea Expressway Corporation.
文摘The widespread adoption of tunnel boring machines(TBMs)has led to an increased focus on disc cutter wear,including both normal and abnormal types,for efficient and safe TBM excavation.However,abnormal wear has yet to be thoroughly investigated,primarily due to the complexity of considering mixed ground conditions and the imbalance in the number of instances between the two types of wear.This study developed a prediction model for abnormal TBM disc cutter wear,considering mixed ground conditions,by employing interpretable machine learning with data augmentation.An equivalent elastic modulus was used to consider the characteristics of mixed ground conditions,and wear data was obtained from 65 cutterhead intervention(CHI)reports covering both mixed ground and hard rock sections.With a balanced training dataset obtained by data augmentation,an extreme gradient boosting(XGB)model delivered acceptable results with an accuracy of 0.94,an F1-score of 0.808,and a recall of 0.8.In addition,the accuracy for each individual disc cutter exhibited low variability.When employing data augmentation,a significant improvement in recall was observed compared to when it was not used,although the difference in accuracy and F1-score was marginal.The subsequent model interpretation revealed the chamber pressure,cutter installation radius,and torque as significant contributors.Specifically,a threshold in chamber pressure was observed,which could induce abnormal wear.The study also explored how elevated values of these influential contributors correlate with abnormal wear.The proposed model offers a valuable tool for planning the replacement of abnormally worn disc cutters,enhancing the safety and efficiency of TBM operations.
基金supported by the National Natural Science Foundation of China(grant No.82405081)Guangdong Basic and Applied Basic Research Foundation(grant No.2025A1515011267)the National Postdoctoral Research Program(certificate number:GZC20230979)+4 种基金the China Postdoctoral Science Foundation(certificate numbers:2023TQ0135 and 2024M751136)Guangzhou Basic and Applied Basic Research(2025A04J3397)the Guangzhou Key Laboratory of Formula-Patterns of Traditional Chinese Medicine(No.202102010014)the Project of Administration of Traditional Chinese Medicine of Guangdong Province of China(No.20232179)the Fundamental Research Funds for the Central Universities(No.21624362).
文摘Background:Renshen Guben oral liquid(RGSB)has the ability to consolidate constitution,restore vitality,and delay the ageing process and the onset of geriatric diseases.RGSB also has potential therapeutic effects on intervertebral disc degeneration(IVDD).This study investigated the therapeutic effects of RGSB on IVDD and explored the underlying mechanisms.Methods:Single-cell sequencing and network pharmacology analyses were conducted in combination to determine the mechanisms of IVDD.Thirty-two C57BL/6J mice were randomly assigned to four groups:the sham operation group,IVDD group,Ibuprofen(IB)group,and RGSB group.All groups except for the sham operation group underwent needle puncture of the caudal IVDs.Behavioral tests,ELISA,PCR,TUNEL staining,and immunohistochemical staining were performed to investigate the therapeutic mechanisms associated with IVDD.Results:Bioinformatics analysis revealed that apoptosis is involved in the development of IVDD and that RSGB might alleviate IVDD by inhibiting apoptosis.After needle puncture,the mice exhibited from thermal allodynia,a decrease in disc height,an increase in the Pfirrmann grade,and destruction of IVDs.Surgery to induce IVDD increased the levels of Matrix Metalloproteinase-3(MMP3),Caspase-6,and Cyt-c in nucleus pulposus cells and the periphery;serum levels of interleukin-1β(IL‐1β)and TNF‐α;and the mRNA levels of IL-6,TNF-α,and IL-1β.Moreover,IVDD decreased the IL-10 mRNA level and the expression of Col-I and BCL2.RSGB reversed these changes.Conclusion:RSGB alleviated IVDD by relieving inflammation and apoptosis and alleviating neuroinflammation.
