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Alzheimer's disease (AD) is one of the most common diseases in the elderly population. Its etiology involves multiple pathogenic factors and pathological links such as abnormal deposition of β amyloid protein (Aβ), hyperphosphorylation of Tau protein, abnormalities of the cholinergic system, oxidative stress, and inflammatory response. However, its specific pathogenesis has not been clarified, and no specific therapeutic drugs have been found. In recent years, more and more studies have paid attention to the potential of chemical components of traditional Chinese medicine (TCM) in the treatment of AD. However, the diversity and complexity of the chemical components of TCM may have a positive impact on multiple pathological links of AD. Researchers have isolated many active components from TCMs, and the effects of treating AD have been confirmed by modern pharmacological studies. Through literature analysis, this article found that the main chemical components of TCM with anti-AD effects were saponins (31%), flavonoids (24%), polysaccharides (20%), lactones (8%), alkaloids (7%), phenols (3%), and other compounds (7%). Among them, ginsenoside, notoginsenoside, epimedium flavones, puerarin, baicalein, schisandra polysaccharide, angelica polysaccharide, ganoderma lucidum polysaccharide, pachyman, huperzine A, berberine, andrographolide, curcumin, emodin, and gastrodin have been extensively studied in terms of their anti-AD effects, and their mechanisms of pharmacological action have been involved in many aspects of AD pathogenesis. This article reviews the anti-AD activities and possible mechanisms of chemical components of TCM, so as to provide a reference for the development of new drugs for the prevention and treatment of AD.
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Portal vein thrombosis (PVT) refers to thromboembolism that occurs in the extrahepatic main portal vein and/or intrahepatic portal vein branches. PVT is the result of the combined effect of multiple factors, but its pathogenesis remains unclear. Animal models are an important method for exploring the pathophysiological mechanism of PVT. Based on the different species of animals, this article reviews the existing animal models of PVT in terms of modeling methods, principles, advantages and disadvantages, and application.
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Cold and heat belong to the eight-principal syndrome differentiation of traditional Chinese medicine, which can reflect the rise and fall of Yin and Yang in the body and the Yin and Yang nature of the disease. At present, traditional Chinese medicine has an inconsistent understanding of cold and heat in acute coronary syndrome. The emphasis on pathogenic factors of cold and heat is biased, and the elements of cold and heat syndrome are not fully reflected in the scale. Therefore, the literature has been reviewed from the perspectives of etiology, pathogenesis, symptom elements, and test signs with drugs. From the perspective of etiology, both cold evil and heat evil can increase the risk of acute coronary syndrome. It was previously believed that acute coronary syndrome occurs frequently in cold climates such as winter and spring. Based on this understanding, hot weather can also induce acute coronary syndrome, and different temperatures have different effects on patients of different ages and with different underlying diseases. In addition, artificial pathogenic factors such as excessive consumption of cold food and refrigeration air conditioners were added. From the perspective of pathogenesis, on the basis of the traditional ''asthenia in origin and asthenia in superficiality'' and ''phlegm stagnation'', it is found that Yin-cold and fire-heat can both cause paralysis of the heart chakra and pain induced by the blockage. The pathogenesis of acute coronary syndrome characterized by heat stagnation and coldness featuring heartburn should be distinguished from gastroesophageal reflux disease. Moreover, the pathogenesis of Yin cold coagulation and pulse stagnation and wind obstruction are different. The acute coronary syndrome is in line with the wind characteristics of frequent changes and can be treated with wind medicine. From the perspective of syndrome elements, the syndrome elements such as cold condensation, heat accumulation, and toxicity are analyzed, and the use of basic syndrome elements and their combination forms facilitates clinical and scientific research. In addition, according to the test sign with the drug, it can be seen that the attributes of cold and heat of traditional Chinese medicine prescriptions for acute coronary syndrome can be explained according to the temperature-sensitive transient receptor potential (TRP) ion channel, thus proving the pathogenesis of cold and heat of acute coronary syndrome.
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Posttraumatic stress disorder(PTSD)is a delayed and persistent mental disorder caused by severe psychological trauma,and the prevalence of PTSD is gradually increasing.This article summarizes the epidemiology,causes and pathogenesis,diagnosis,treatment,future and prospect of PTSD,in order to provide reference for the prevention,diagnosis and treatment of PTSD.
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In recent years,the prevalence of childhood obesity has increased rapidly,and obesity can seriously affect physical and mental health of children and adolescents,and is likely to extend into adulthood. The onset and development of childhood obesity is related to multiple factors such as genetic predisposition and environment. So far,more and more studies have found that the gut microbiota,as an important part of the internal environment,is closely related to childhood obesity. Perturbed gut microbiota and its derived metabolites such as short-chain fatty acids,bile acids,indole and their derivatives are widely involved in the onset and development of childhood obesity. At present,regulating the compositions and function of gut microbiota through probiotics and prebiotics,fecal microbiota transplantation,dietary intervention,and bariatric surgery is a new direction for the prevention and treatment of obesity. This paper reviews the research progress on the association between gut microbiota and childhood obesity,in order to provide novel insights for prevention and intervention of childhood obesity based on gut microbiota.
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Neurofibromatosis type 1(NF1)is one of the most common autosomal dominant disorders. The disease is caused by mutations in the NF1 gene,which can involve multiple systems and have a variety of clinical manifestations,including café au lait macules,lisch nodules,neuroglioma,autism spectrum disorder,learning difficulties,neurofibromas,and skeletal dysplasia,et al.In previous studies on the pathogenesis of NF1,most of them have focused on the regulation of the RAS signaling pathway by neurofibromin. In recent years,researchers start exploring pathways other than RAS signaling to explore the potential functions of neurofibromin. This article reviews the research progress on the pathogenesis of NF1 in recent years,aiming to provide new ideas for treatment.
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Congenital heart disease(CHD)is a common congenital anomaly that is the leading cause of death among children under the age of five years with birth defects in both developed and developing countries. With the increasing prevalence of CHD,the importance of early diagnosis and intervention of CHD is well accepted. Prenatal ultrasonography is routinely applied for the screening of CHD but many factors influence its diagnostic accuracy. Biomarker testing is a simple and rapid method that can be used as an adjunct to prenatal screening for CHD. This review aims to provide new ideas for the early diagnosis of children with CHD by exploring the pathogenesis of biomarkers in CHD. In recent years,many studies have been devoted to the exploration of biomarkers related to CHD,and the studies on biomarkers in CHD are summarized from three aspects:epigenetics,proteomics and environmental factors.
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Hypovolemic and hemodynamic disorders,autonomic nervous dysfunction and hyperadrenergic state are recognized pathogenesis of postural tachycardia syndrome(POTS). According to this,POTS can be divided into three types:hypovolemic POTS,neurogenic POTS and hyperadrenergic POTS. Autoimmune abnormalities,changes in hormone levels,and gene mutations may also cause POTS. In addition,some patients have joint overactivity syndrome,functional gastrointestinal disorders,Ehlers Danlos syndrome,mast cell activation disorders and other diseases.Therefore,POTS is a complex clinical syndrome that may involve multiple mechanisms.This article aims to offer clinicians an improved understanding of the pathogenesis of pediatric POTS through a comprehensive review of this disease.
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Virus is one of the common causes of respiratory tract infection in children.Viral infection involves the action of multiple immune cells and inflammatory mediators,understanding the immune mechanism of virus-host interaction during respiratory infection may be helpful for etiological diagnosis of viral infections.As the main immune cells of the lungs,alveolar macrophages on the mucosal surface of the respiratory tract play an important role in maintaining pulmonary immune homeostasis(immune monitoring,initiation and regulation of inflammatory response,killing pathogens)due to their unique position.This article will briefly review the immune regulation mechanism of alveolar macrophages in the occurrence and development of respiratory tract viral infection in children,in order to provide reference for the prevention and treatment of viral infection.
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Uremic pruritus (UP) is a common complication in patients with end-stage renal disease, which seriously reduces the quality of life of patients. Compared with the internal treatment of TCM, the external treatment of TCM for UP is simpler and more effective, and can avoid the first pass effect caused by oral drugs and may cause liver and kidney damage. The treatment methods mainly include external washing of TCM, medicated bath, fumigation, wet compress, enema, scraping, acupuncture, auricular point sticking, acupoint application, acupoint iontophoresis, autologous blood acupoint injection and so on. At present, most studies are based on the conventional treatment of Western medicine, and the addition of external treatment of TCM can improve the efficacy, and has certain advantages in improving itching symptoms, inflammatory indicators, sleep quality, anxiety and depression. Some studies have selected parathyroid hormone, blood phosphorus, CRP, IL-6, histamine, SCr, BUN, β2-microglobulin and other indicators to evaluate the efficacy. The results suggest that external treatment of TCM can improve the micro-inflammatory state of patients and protect renal function, but further mechanism research is needed. The existing research has the following problems: the clinical efficacy evaluation scale is not uniform, and it is difficult to compare and summarize horizontally; the relief of pruritus symptoms is based on the scale evaluation, which is subjective; the course of treatment is short, and the long-term efficacy and safety can not be evaluated; some studies do not specify the patients' syndrome type, which is difficult to reflect the advantages of TCM syndrome differentiation and treatment, and needed to be improved in the future.
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Objective To investigate the clinical characteristics of stasis-toxin pathogenesis in patients with non-small cell lung cancer(NSCLC)of blood stasis and qi stagnation type,and to explore the interventional mechanism of adjuvant therapy with Bufei Huayu Decoction.Methods Seventy-eight patients with NSCLC of blood stasis and qi stagnation type admitted to the Department of Respiratory Medicine of Liu'an Hospital of Traditional Chinese Medicine from January 2021 to September 2022 were selected as the NSCLC group,and 71 volunteers who underwent physical examination during the same period served as the healthy control group.The clinical characteristics of stasis-toxin pathogenesis in the NSCLC group were observed,and the differences in the indicators of coagulation function were compared between NSCLC group and the healthy control group.According to the therapy,the NSCLC patients were divided into Bufei Huayu Decoction group(40 cases)and conventional treatment group(38 cases).The conventional treatment group was treated with conventional chemotherapy,while Bufei Huayu Decoction group was treated with Bufei Huayu Decoction together with conventional chemotherapy.Three weeks constituted one course of treatment,and the treatment lasted for 2 courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,coagulation function,immune function,serum nitric oxide(NO),vascular endothelial growth factor(VEGF)level in Bufei Huayu Decoction group and conventional treatment group were observed before and after treatment.Moreover,the clinical efficacy of the two groups and the occurrence of adverse reactions were compared during the treatment period.Results(1)NSCLC patients were classified into the clinical stages Ⅲ and Ⅳ and the pathological types of squamous carcinoma and adenocarcinoma,had the high proportion of KPS scores lower than 70,and were scored with high TCM syndrome scores,suggesting that the illness condition of patients with NSCLC was serious.Compared with the healthy control group,plasminogen time(PT)and thrombin time(TT)in NSCLC patients were significantly shortened,and levels of fibrinogen(FIB)and D-dimer(D-D)were significantly increased,and the differences were statistically significant(P<0.01).(2)After 6 weeks of treatment,the total effective rate and total stability rate of Bufei Huayu Decoction group were 32.50%(13/40)and 85.00%(34/40),which were significantly superior to those of the conventional treatment group[versus 13.16%(5/38)and 60.53%(23/38)],and the differences were statistically significant(P<0.05).(3)After 3 weeks of treatment,obvious improvement was presented in the scores of all the TCM symptoms of fatigue,chest distress and shortness of breath,stabbing pain in the chest,and blood stasis in the vessels and collaterals of Bufei Huayu Decoction group and in the scores of the fatigue,chest distress and shortness of breath of the conventional treatment group when compared with those before treatment(P<0.05).After 6 weeks of treatment,all of the TCM syndrome scores of the two groups were improved compared with those before treatment and after three weeks of treatment(P<0.05).The intergroup comparison showed that except for the scores of chest distress and shortness of breath after 3 weeks of treatment,the effect on improving all of the TCM syndrome scores in Bufei Huayu Decoction group was significantly superior to that in the conventional treatment group after 3 and 6 weeks of treatment(P<0.05 or P<0.01).(4)After 6 weeks of treatment,the levels of coagulation function indicators of PT,TT,FIB and D-D in the Bufei Huayu Decoction group were significantly improved compared with those before treatment(P<0.05),while only FIB and D-D in the conventional treatment group were improved compared with those before treatment(P<0.05).The intergroup comparison showed that Bufei Huayu Decoction group had stronger effect on improving the levels of PT,FIB and D-D than the conventional treatment group(P<0.05).(5)After 6 weeks of treatment,the serum NO and VEGF levels in both groups were significantly lower than those before treatment(P<0.05),and the effect on lowering serum NO and VEGF levels of the Bufei Huayu Decoction group was significantly superior to that of the conventional treatment group(P<0.01).(6)After 6 weeks of treatment,the immune function parameters of CD3+,CD4+ levels and CD4+/CD8+ ratio in the Bufei Huayu Decoction group were increased(P<0.05)and CD8+level was decreased(P<0.05)as compared with those before treatment,whereas CD3+,CD4+ levels and CD4+/CD8+ ratio in the conventional treatment group were decreased(P<0.05)and CD8+ level was increased(P<0.05).The intergroup comparison showed that the effect of Bufei Huayu Decoction group on the increase of CD3+,CD4+ levels and CD4+/CD8+ ratio and the effect on the decrease of CD8+ level were significantly superior to those of the conventional treatment group(P<0.01).(7)In terms of the quality of life,the KPS scores of patients in the two groups after 6 weeks of treatment were significantly higher than those before treatment(P<0.05),and the effect of Bufei Huayu Decoction group on the increase of KPS scores was significantly superior to that of the conventional treatment group(P<0.01).(8)During the course of treatment,the incidence of adverse reactions such as gastrointestinal reactions and alopecia in the two groups was not statistically significant(P>0.05),while the incidence of hepatic and renal impairment,bone marrow suppression,and toxicity of oral mucosa in Bufei Huayu Decoction group was significantly lower than that of the conventional treatment group(P<0.05 or P<0.01),suggesting that Bufei Huayu Decoction group reduced the adverse reactions induced by chemotherapy to a certain extent.Conclusion Patients with NSCLC of blood stasis and qi stagnation type generally have advanced disease progression and high blood coagulation,which is consistent with the stasis-toxin pathogenesis in TCM.The use of Bufei Huayu Decoction against the stasis-toxin pathogenesis can significantly improve patients'TCM syndrome scores and coagulation function,down-regulate the levels of serum NO and VEGF,and improve the immune function,which brings about the enhancement of clinical efficacy and quality of life,and the reduction of adverse reactions caused by chemotherapy,with a high safety.
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This article aims to analyze LI Fei's academic thinking and experience in treating facial paralysis.LI Fei proposes that the diagnosis and treatment of facial paralysis should follow the principle of"identify the cause of the disease when it is occured at first time,followed by exploring the pathogenesis of the disease,then differentiating the syndrome and treating the disease,and recognizing the syndrome and treating the disease",and that the basic treatment principle should be"dispelling wind and unblocking the collaterals,regulating the tendons and meridians".In clinical treatment,"put emphasis on anatomy,treat the disease according to symptoms"is the basic policy;meanwhile,integrating Chinese and western theories,combining the anatomical structure of the expression muscle,dynamically judging the recovery of nerves and muscles,and selecting the corresponding empirical acupoints according to the symptoms.LI Fei emphasizes the integration of theories and summarizes the"triple"methods of differentiation by reasoning,staging and symptoms,and the"triple"theory of treatment by regulating menstruation,tendon and spirit,which is worthy of reference in the clinic.
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Hypoxia-inducible factor-1α(HIF-1α)is a nuclear transcription factor.Under high glucose and hypoxia conditions,the expression of HIF-1α is elevated,result in the increased expression of its downstream target genes VEGF,HO-1 and BNIP3,which affect angiogenesis,extra cellular matrix deposition,iron metabolism,and mito-phagy,participating in the occurrence and development of diabetic kidney disease(DKD).In addition,HIF-1α promotes inflammation and renal fibrosis by affecting the production of cytokines in DKD.
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Helicobacter pylori(HP)infection is a Class Ⅰ carcinogen in gastric cancer,closely related to the occurrence of gastric cancer.Many studies have shown that HP eradication has a preventive effect on gastric cancer.However,2.7%-6.1%of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection(ESD)can still develop metachronous gastric cancer(MGC),and the mechanism of its occurrence is still unclear.In this review,the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication,the excessive proliferation of gastric mucosa epithelial cells,the accumulation of genetic abnormalities,the homeostasis imbalance of the epigenetic group,changes in immune microenvironment,the abnormality of stem cells in gastric mucosa,chromatin accessibility,and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.
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Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T>G and c.1117C>T,her father(Ⅱ3)carried vWF gene c.7288-9T>G heterozygous mutation,and vWF gene c.1117C>T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C>T and c.7288-9T>G may be the molecular mechanism leading to type 2A vWD in the proband.
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Chronic lymphocytic leukemia(CLL)is one of small B-cell lymphomas and leukemias,characterized as a clonal disease of mature B cells.The disease is remarkably heterogeneous,with the majority of patients having an indolent course,yet they are currently incurable.Abnormal signaling pathways are indispensable in the pathogenesis of CLL.In CLL,the common abnormalities of signaling pathways include B-cell receptor(BCR)signaling,apoptosis,nuclear factor kappa B(NF-κB)signaling and Notch signaling.According to the target in signaling pathways,a series of targeted drugs,such as Bruton's tyrosine kinase(BTK)inhibitors(ibrutinib,zanubrutinib),phosphorylate phosphoinositide 3-kinase(PI3K)inhibitor(duvelisib)and B-cell leukemia/lymphoma 2(BCL2)inhibitor(venetoclax),which have significantly changed the prognosis of patients in clinic.Other targeted drugs,such as fenebrutinib,nemtabrutinib and umbralisib,as well as chimeric antigen receptor T-cell(CAR-T)therapy developed in the field of immuno-oncology and T cell engineering,are currently under trial,with more personalized treatment modalities being explored,which may become potential drug targets in the future.In this paper,relevant literature of CLL was reviewed,and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.
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Tic disorder (TD) is one of the typical neurodevelopmental disorders in childhood.More studies have confirmed that the etiology and pathogenesis of TD are related to genetics, environment, immunology, and psychology, etc.Identifying the etiology and pathogenesis helps to guide the treatment of TD.This paper reviews the research progress in the etiology and pathogenesis of pediatric TD in recent years.
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Tic disorder (TD) is a neurodevelopmental disorder that occurs in childhood, characterized by involuntary movements or vocal tics and occasionally accompanied by various comorbidities.It may seriously affect children′s daily life, learning and social activities.Exploring its etiology and pathological mechanisms and developing drugs require extensive research on animal models.There are currently various methods for constructing TD models, including induced and spontaneous animal models, such as induced animal models with abnormal neurotransmitters and immune functions and spontaneous animal models based on genetic engineering.However, no animal model can fully match the manifestations of TD.This article summarizes the commonly used animal models for TD to provide references for exploring pathological mechanisms and developing drugs.
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Endometriosis is a common chronic gynecological disease,and its pathogenesis has not been fully elucidated.Mesenchymal stem cells are a kind of pluripotent stem cells with multi-directional differentiation potential derived from mesoderm,which can differentiate into a variety of tissues and organs.Endometrial mesenchymal stem cells,menstrual blood-derived mesenchymal stem cells,adipose mesenchymal stem cells,bone marrow mesenchymal stem cells and umbilical cord blood mesenchymal stem cells can participate in the pathogenesis of endometriosis from cell proliferation and differentiation,ectopic migration,angiogenesis,inflammatory response and fibrosis formation,and play a certain role in progression of the disease.Mesenchymal stem cells provide new ideas for elucidating the pathogenesis of endometriosis,and may also become a potential method for the treatment of endometriosis.
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BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.