BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.

BACKGROUND:At present,bone marrow mesenchymal stem cells are the main seed cells used in cell therapy for the treatment of intervertebral disc degeneration.However,the use of bone marrow mesenchymal stem cells as seed cells for the regeneration of fibrous rings is at risk of heterotopic ossification and teratoma at the repair site.Therefore,it is of great economic and social significance to find a new kind of seed cells for tissue engineering of annulus fibrosus for the treatment of intervertebral disc degeneration. OBJECTIVE:To isolate and purify rat annulus fibrosus-derived stem cells by adherent method combined with fibronectin differential adhesion screening method,and to observe its purification effect and biological characteristics. METHODS:Annulus fibrosus tissue was obtained from a SD rat intervertebral disc.Primary annulus fibrosus-derived stem cells were obtained by the mechanical-enzymatic digestion method.Annulus fibronectin differential adhesion method was used to purify annulus fibrosus-derived stem cells.Morphological changes and proliferation of cells were observed through a microscope.The expression levels of stem cell markers were detected by immunofluorescence technique and qPCR.The screened cells were subjected to multi-lineage cell differentiation and characteristic gene detection. RESULTS AND CONCLUSION:(1)The purified cells grew well,and most of them were angular and star-shaped multi-process cells,which had good proliferation ability.(2)Cells were positive for cell membrane surface antigens CD73,CD90 and CD105,while negative for CD45 and CD34.(3)After specific induction,cells could successfully differentiate into osteoblasts,chondroblasts and lipoblasts.(4)Collagen-I,Runx-2 after osteogenic induction,Collagen Ⅱ,Sox-9 after chondrogenic induction,and PPAR-γ and LPL after lipogenic induction were highly expressed in cells,and the difference was significant compared with that before induction(P<0.05).(5)These findings confirm that the adherent method combined with fibronectin differential adhesion method is effective enough to screen,isolate and purify rat annulus fibrosus-derived stem cells,and has good cell biological properties,good proliferation ability and multiple differentiation potential.

Intervertebral disc degeneration(IDD) is the pathological basis of spinal diseases. With the development and change of working and living style, IDD gradually presents the trend of younger in recent years. The effective prevention and treatment of IDD has become a hotspot in clinical research. Recent studies have shown that oxidative stress plays an important role in IDD. The disruption of reactive oxygen species balance in cells or the body leads to changes in extracellular matrix and intervertebral disc cell phenotype, which induces oxidative stress of intervertebral disc and leads to IDD. Oxidative stress can affect the development of IDD through apoptosis, autophagy, senescence and extracellular matrix of intervertebral disc. Currently, opioids and drugs for promoting blood circulation and pain relief are commonly used in clinical treatment of IDD, which can alleviate some symptoms to a certain extent, but is easy to induce gastrointestinal and other adverse reactions. Meanwhile, due to the long treatment cycle and poor patient compliance to a certain extent, which brings great difficulties to the treatment. At the same time, traditional Chinese medicine plays an important role in the treatment of IDD due to its advantages of low cost and fewer adverse reactions. With the in-depth research of modern technologies such as molecular biology and network pharmacology, it has been found that traditional Chinese medicine can intervene in the expression of oxidative stress-related functions, namely, slowing down apoptosis, autophagy and degradation of extracellular matrix, etc, to play a role in the treatment of IDD. In this paper, the role of oxidative stress in IDD and the research results on the intervention of traditional Chinese medicine in oxidative stress will be expounded, in order to provide reference for the prevention and treatment of IDD by traditional Chinese medicine.

Objective:To measure the beam stability of the electron FLASH radiotherapy accelerator developed by the Institute of Applied Electronics of Chinese Academy of Engineering Physics and to evaluate the performance of scintillator, fast current sensor (FCT) and graphite under the electron FLASH beam.Methods:Each continuous beam exit deviation and each pulse deviation at the electron FLASH radiotherapy accelerator in the same working state were measured. The correlation among three monitors and the measured dose of the accelerator at different electron beam energy (controlled by changing the charging voltage) and different beam pulse numbers were compared, which were validated by a Monte Carlo simulation procedure.Results:At the first high pressure, the first 10 scintillators and FCT signals were relatively large, approximately 2% deviation compared with the average value of 400 pulses. Among 40 beam outflows, the deviation between each pulse was within ±5%. In the accelerator steady state, each beam outflow deviation was within ±1%. Both simulated and measured values showed that the monitor could not be used for dose monitoring at different electron beam energy. However, when the energy was the same, only the number of beam pulses was changed, and linear relationship was observed between the number of the three monitors and the dose measured by the film (all R 2 > 0.999). Conclusions:The beam deviation of each beam outflow of this electron FLASH accelerator is within ±1%. Under the stability of the accelerator beam, the scintillator, FCT and graphite can meet the dose monitoring of the target area, which can provide reference for dose monitoring for subsequent biological experiments.

Objective To investigate the differences in blood pressure phenotypes,renal pathological changes,and related pathogenic pathways in genetically diverse hypertensive mice obtained from 13 strains.Methods The genotypes of Cckbr+/+,Cckbr+/-and Cckbr-/-were obtained by hybridization of 13 strains of genetically diverse mice with Cckbr-/-mice.Blood pressure was measured with a noninvasive blood pressure analysis system(BP-2000).The expression of CCKBR protein in mouse kidney tissue was detected by Western Blot,and the pathological changes in mouse kidney tissue were detected by hematoxylin-eosin(HE)staining and immunohistochemistry(IHC).The pathogenic pathways related to essential hypertension were screened by RNA sequencing.Results In three specific mouse strains(A/J,LOT,and FIM),the systolic blood pressure(SBP)was significantly different between the Cckbr-/-and Cckbr+/+groups.HE staining and IHC showed that hypertension caused a certain degree of renal injury in the mice.Gene Ontology(GO)and pathway enrichment analysis showed that differentially expressed genes were enriched in metabolic processes and circadian rhythm regulation.Conclusions Genetically diverse mice can effectively simulate the genetic background of the population and provide a new resource for studying the pathogenic genes related to essential hypertension.

Mice ; Animals ; Humans ; Disease Models, Animal

Intervertebral disc degeneration is one of the common causes of chronic low back pain. As a common spinal disease， its clinical symptoms are mainly low back pain and limited function， which seriously affects physical and psychological health. Because of its complex and unclear pathogenesis， the treatment of intervertebral disc degeneration has been the focus of scientific researchers and clinical workers. At present， the treatment of intervertebral disc degeneration mainly includes non-surgical therapy and surgical therapy， which can alleviate the clinical symptoms of patients to a certain extent， but easily induce new complications， and it is difficult to restore the normal physiological function of the intervertebral disc. In recent years， along with the advanced research on matrix metalloproteinases （MMPs） in the tissues of intervertebral disc degeneration， it has been found that MMPs can be used as molecular therapeutic targets. The expression of MMPs in the intervertebral disc tissues can be regulated by reducing the content and composition of the extracellular matrix of the intervertebral disc， so as to slow down intervertebral disc degeneration and even reverse the occurrence of intervertebral disc degeneration. This treatment is expected to delay intervertebral disc degeneration caused by changes in extracellular matrix composition or content. In recent years， with the continuous development of network pharmacology and bioinformatics research， a large number of researchers have explored the treatment of intervertebral disc degeneration by traditional Chinese medicine （TCM） and found that TCM can reduce the degradation of extracellular matrix by inhibiting the expression of MMPs， thus alleviating the symptoms of intervertebral disc degeneration and slowing down the progression of intervertebral disc degeneration. This paper reviewed the research progress of TCM intervention in MMP expression in the treatment of intervertebral disc degeneration， aiming at providing references for the application of TCM in the prevention and treatment of intervertebral disc degeneration.

Osteoporosis is a chronic skeletal disease characterized by low bone mass， destruction of bone tissue microarchitecture， and imbalance of bone homeostasis， leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species （ROS） and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen， carbon monoxide， and free iron. The metabolites can scavenge ROS， thereby exerting an antioxidant effect in cells. At present， domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target， multi-channel， and multi-level advantages. Chinese medicine can resist oxidative stress， inflammatory response， and apoptosis by regulating the Nrf2/HO-1 signaling pathway， thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis， to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time， a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted， to provide a theoretical basis for further precise treatment of osteoporosis.

External treatment of Traditional Chinese Medicine (TCM) is a common treatment for lumbar disc herniation, which mainly includes fumigation and washing of TCM, and hot ironing therapy. It can cooperate with oral administration of TCM, Tuina, acupuncture and other therapies to play a synergistic effect and enhance the efficacy. External application of TCM in the treatment of lumbar intervertebral disc herniation is effective with long duration, easy-operated and safe It has showed curative effect in alleviating clinical symptoms and improving lumbar function. Its mechanism mainly includes regulating nerve inflammatory reaction, improving hemorheology and exerting analgesic effect.

Gut microbiota plays an important role in development of diabetes with frailty. Therefore, it is of great significance to study the structural and functional characteristics of gut microbiota in Chinese with frailty. Totally 30 middle-aged and the aged participants in communities with diabetes were enrolled in this study, and their feces were collected. At the same time, we developed a metagenome analysis to explore the different of the structural and functional characteristics between diabetes with frailty and diabetes without frailty. The results showed the alpha diversity of intestinal microbiota in diabetes with frailty was lower.
Aged ; Diabetes Mellitus ; Epstein-Barr Virus Infections ; Frailty ; Gastrointestinal Microbiome ; Herpesvirus 4, Human ; Humans ; Middle Aged