Ischemic stroke （IS） is an acute cerebrovascular disease caused by insufficient blood supply to the brain， resulting in brain tissue necrosis and neurological dysfunction. It is characterized by impaired motor， language， sensory， cognitive， and other functions. The pathogenesis involves inflammatory responses， excitotoxicity of excitatory amino acids， and mitochondrial dysfunction. IS with a high incidence， high mortality， high disability， and a high recurrence rate is the leading cause of death in China. At present， Western medical therapies mainly focus on vascular recanalization， including thrombolysis and mechanical thrombectomy. However， due to the possibility of cerebral hemorrhage and edema， narrow time windows， and contraindications associated with intravascular therapy， only a few patients can benefit from these therapies， which greatly limit their clinical application. IS belongs to the categories such as stroke， hem iplegia， and major syncope in traditional Chinese medicine （TCM）. It is mainly caused caused by wind， fire， phlegm， and stasis， which lead to imbalance of Yin and Yang， disorder of Qi and blood， and invasion of clear orifices. The common treatment methods include calming the liver and dispelling wind， resolving phlegm and unblocking meridians， and activating blood and resolving stasis. TCM acting on multiple pathways and targets with low toxicity and side effects has definite effects in improving the prognosis and reducing the recurrence rate， being worthy of promotion and research. Brain-derived neurotrophic factor （BDNF） plays a key role in promoting neurogenesis and increasing synaptic plasticity. During the progression of IS， BDNF binds to tyrosine kinase receptor B （TrkB） to initiate intracellular signaling cascades， thus exerting neuroprotective effects. Studies have shown that TCM can regulate the BDNF/TrkB signaling pathway， treating IS by regulating synaptic plasticity and promoting neural repair. This paper summarizes and generalizes the mechanisms of active components， single herbs， and compound prescriptions of TCM in regulating the BDNF/TrkB signaling pathway in the treatment of IS through the review of domestic and foreign literature in recent years， aiming to provide a theoretical basis and treatment reference for the treatment of IS with TCM.

BACKGROUND:Lysosomal storage diseases,as a group of rare genetic metabolic disorders,exhibit complex pathogenesis often leading to dysfunction of cells,tissues,and organs.Current therapeutic approaches have certain limitations.Stem cell transplantation,as an emerging treatment method,offers new options for patients with lysosomal storage diseases.OBJECTIVE:To review the mechanisms of action of stem cells in regulating lysosomes for the treatment of lysosomal storage diseases and explore the feasibility of traditional Chinese medicine in treating such diseases,providing new insights for the treatment of lysosomal storage diseases with stem cells.METHODS:Relevant literature from 2010 to 2024 was searched in CNKI and PubMed databases using keywords"stem cells,lysosomal storage disease,lysosome"in English and Chinese.Ultimately,78 articles were included for review and analysis.RESULTS AND CONCLUSION:(1)Stem cells treat lysosomal storage diseases by regulating lysosomes primarily through three aspects:regulating stem cell differentiation and replacement,improving intercellular communication and the microenvironment,and enhancing lysosomal enzyme expression through gene editing.(2)Stem cells have achieved significant effects in the treatment of some lysosomal storage diseases,such as Niemann-Pick disease,mucopolysaccharidoses,Gaucher disease,and metachromatic leukodystrophy.(3)The procedure for stem cell transplantation needs further optimization.Adverse reactions post-transplantation urgently need to be addressed,and the efficiency and safety of gene-modified stem cells also need to be further improved.In the future,more research on the treatment of lysosomal storage diseases with traditional Chinese medicine is required to reveal the relevant mechanisms for the treatment of lysosomal storage diseases with traditional Chinese medicine.

BACKGROUND:Lysosomal storage diseases,as a group of rare genetic metabolic disorders,exhibit complex pathogenesis often leading to dysfunction of cells,tissues,and organs.Current therapeutic approaches have certain limitations.Stem cell transplantation,as an emerging treatment method,offers new options for patients with lysosomal storage diseases.OBJECTIVE:To review the mechanisms of action of stem cells in regulating lysosomes for the treatment of lysosomal storage diseases and explore the feasibility of traditional Chinese medicine in treating such diseases,providing new insights for the treatment of lysosomal storage diseases with stem cells.METHODS:Relevant literature from 2010 to 2024 was searched in CNKI and PubMed databases using keywords"stem cells,lysosomal storage disease,lysosome"in English and Chinese.Ultimately,78 articles were included for review and analysis.RESULTS AND CONCLUSION:(1)Stem cells treat lysosomal storage diseases by regulating lysosomes primarily through three aspects:regulating stem cell differentiation and replacement,improving intercellular communication and the microenvironment,and enhancing lysosomal enzyme expression through gene editing.(2)Stem cells have achieved significant effects in the treatment of some lysosomal storage diseases,such as Niemann-Pick disease,mucopolysaccharidoses,Gaucher disease,and metachromatic leukodystrophy.(3)The procedure for stem cell transplantation needs further optimization.Adverse reactions post-transplantation urgently need to be addressed,and the efficiency and safety of gene-modified stem cells also need to be further improved.In the future,more research on the treatment of lysosomal storage diseases with traditional Chinese medicine is required to reveal the relevant mechanisms for the treatment of lysosomal storage diseases with traditional Chinese medicine.

OBJECTIVES: To exple the mechanism of Qixiong Zuogui Granules (QXZG) for enhancing synaptic plasticity in aging rats. METHODS: Forty SD rats were randomized into control group, aging model group, donepezil treatment group, and QXZG treatment group (n=10). Except for the control rats, all the rats were subjected to daily intraperitoneal injection of D-galactose for 8 consecutive weeks to induce brain aging, and donepezil hydrochloride and QXZG suspension were administered by gavage during modeling. After the interventions, the rats were evaluated for general conditions, behavioral changes, oxidative stress indicators, hippocampal pathologies, and expressions of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, p16, and synaptic plasticity-associated proteins. RESULTS: The rats in the model group exhibited obvious aging phenotypes such as yellowing of the teeth and hair, body weight loss, and impaired learning and memory abilities, with decreased serum SOD and GSH-Px activities and increased serum MDA level. The rat models also showed obvious pathological changes, reduced Nissl bodies, and elevated p16 protein expression in the hippocampal CA1 region, with significantly decreased expression levels of BDNF, TrkB, CREB and synaptic plasticity proteins SYN, GAP43, and PSD95. Treatment with QXZG alleviated the aging phenotypes in the rat models, improved their learning and memory abilities and pathological changes in the hippocampal CA1 region, reduced oxidative stress and p16 protein expression, and promoted the expressions of the BDNF/TrkB pathway proteins and synaptic plasticity proteins. CONCLUSIONS QXZG enhances synaptic plasticity and reduces oxidative stress in aging rats possibly by upregulating the BDNF/TrkB signaling pathway proteins, thereby delaying brain aging and improving learning and memory abilities of the rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Neuronal Plasticity/drug effects* ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism* ; Rats ; Aging ; Drugs, Chinese Herbal/pharmacology* ; Male ; Oxidative Stress ; Hippocampus/metabolism*

Objective To exple the mechanism of Qixiong Zuogui Granules(QXZG)for enhancing synaptic plasticity in aging rats.Method Forty SD rats were randomized into control group,aging model group,donepezil treatment group,and QXZG treatment group(n=10).Except for the control rats,all the rats were subjected to daily intraperitoneal injection of D-galactose for 8 consecutive weeks to induce brain aging,and donepezil hydrochloride and QXZG suspension were administered by gavage during modeling.After the interventions,the rats were evaluated for general conditions,behavioral changes,oxidative stress indicators,hippocampal pathologies,and expressions of the brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrkB)pathway,p16,and synaptic plasticity-associated proteins.Results The rats in the model group exhibited obvious aging phenotypes such as yellowing of the teeth and hair,body weight loss,and impaired learning and memory abilities,with decreased serum SOD and GSH-Px activities and increased serum MDA level.The rat models also showed obvious pathological changes,reduced Nissl bodies,and elevated p16 protein expression in the hippocampal CA1 region,with significantly decreased expression levels of BDNF,TrkB,CREB and synaptic plasticity proteins SYN,GAP43,and PSD95.Treatment with QXZG alleviated the aging phenotypes in the rat models,improved their learning and memory abilities and pathological changes in the hippocampal CA1 region,reduced oxidative stress and p16 protein expression,and promoted the expressions of the BDNF/TrkB pathway proteins and synaptic plasticity proteins.Conclusion QXZG enhances synaptic plasticity and reduces oxidative stress in aging rats possibly by upregulating the BDNF/TrkB signaling pathway proteins,thereby delaying brain aging and improving learning and memory abilities of the rats.

OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules,and determine the contents of 12 chemical components.METHODS Identification and content determination were performed by using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1％formic acid solution(gradient elution);the electrospray ion source was used to scan in the positive ion multi-reaction detection mode.The mass charge ratio(m/z)631.3→546.4,631.3→921.4 was the detection ion pair for tortoiseshell glue,and the m/z 765.4→554.0,765.4→733.0 was the detection ion pair for antler glue.The determination method for 12 chemical components was as follows:Accucore C18 column,methanol-0.1％formic acid as mobile phase(gradient elution);scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode.RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min,respectively;the linear relationship of 12 chemical components was good within their respective concentration ranges,such as astragaloside Ⅳ,calycosin-7-O-β-D-glucoside,calycosin,chlorogenic acid,ferulic acid,betaine,amygdalin,rutin,hydroxysafflor yellow A,hyperoside,loganin,cyasterone(r＞0.999);RSDs for precision,stability(24 h)and reproducibility tests were all less than 5％.The average sample recovery rates ranged from 98.04％to 101.08％.The average contents of 12 components were 1.83,25.73,13.76,56.71,23.80,49.82,807.49,15.01,317.02,60.21,202.71 and 17.70 μg/g,respectively.CONCLUSIONS In this study,tortoiseshell glue and antler glue in Qixiong zuogui granules are identified,and the contents of 12 chemical components therein are determined.This provides a reference for the quality control of this granule.

Cerebral ischemia/reperfusion injury （CIRI） is a complex cascade reaction process in which the blood flow and oxygen supply of brain tissue in the infarcted area recover after cerebral ischemia， resulting in secondary injury of ischemic brain tissue. At present， thrombolysis as soon as possible and restoration of cerebral blood supply are still the only strategies for the treatment of stroke， but a considerable number of patients' symptoms will be more serious after reperfusion， making patients face adverse outcomes such as neurological function injury and even death and seriously affecting the quality of life and safety of patients. Therefore， an in-depth exploration of the mechanism and treatment strategy of CIRI has important clinical significance. The phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is one of the classic anti-apoptosis/reproductive-promoting signal transduction pathways， which is responsible for cell proliferation， growth， and differentiation. It is the key cascade signaling pathway of CIRI， located at the core site in many mechanisms such as mitochondrial disorder， apoptosis， autophagy， oxidative stress， and inflammation. It is closely related to the occurrence and development of CIRI. Traditional Chinese medicine has been used in the clinical treatment of stroke and its complications for thousands of years， and the clinical effect of traditional Chinese medicine in the prevention and treatment of CIRI has been affirmed by a large number of research results in recent years. It is further clarified that the monomers， active components， and their compound prescriptions of traditional Chinese medicine can directly or indirectly regulate the PI3K/Akt signaling pathway by virtue of the biological advantages of multi-targets， multi-components， and multi-pathways and play an overall protective role in CIRI. By analyzing the related research progress of traditional Chinese medicine in China and abroad in recent years， the authors summarized the role and mechanism of regulating the PI3K/Akt signaling pathway in the prevention and treatment of CIRI， so as to provide further theoretical basis for the study of the mechanism of clinical prevention and treatment of CIRI.

BACKGROUND:Endogenous neurogenesis and exogenous stem cell transplantation in the brain show great therapeutic potential for neurological diseases including ischemic stroke,repairing and replacing lost neurons,promoting synaptic remodeling,and inhibiting apoptosis.Traditional Chinese medicine and compound therapy for supplementing qi,activating blood circulation and inducing resuscitation for the treatment of neurological dysfunction after ischemia have certain advantages,targeting nerve repair through a variety of ways,including promoting endogenous neurogenesis and exogenous stem cell survival,proliferation,homing,and inducing neuronal differentiation. OBJECTIVE:To summarize the mechanism of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke,in order to provide a reference for the research and treatment of new drugs in ischemic stroke. METHODS:The articles from CNKI and PubMed databases about traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation in promotion of nerve repair in the acute phase of ischemic stroke from 2010 to 2022 were searched,with"supplementing qi and activating blood circulation;inducing resuscitation;traditional Chinese medicine(TCM);compounds;ischemic stroke;nerve repair;stem cells"as Chinese and English search terms.After excluding old and duplicate views,the retrieved literature was analyzed and collated,and a total of 124 articles were included for analysis. RESULTS AND CONCLUSION:(1)The definition of stem cells,ischemic stroke and the nerve repair pathway in the acute phase of ischemic stroke were sorted out.(2)The mechanism of action of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke was summarized,mainly including promoting stem cell proliferation,improving stem cell viability and survival rate,promoting nerve cell homing,inducing stem cell differentiation to neurons,inhibiting apoptosis of nerve cells,promoting axon regeneration,regulating angiogenesis and remodeling,improving the level of neurotrophic factors and repairing the integrity of the blood-brain barrier.(3)Through the existing research,the relevant factors and signaling pathways of traditional Chinese medicines and compounds for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke were summarized,such as Nestin protein expression,DCX protein expression,brain-derived neurotrophic factor,vascular endothelial growth factor and Wnt/β-catenin signaling pathway,Notch signaling pathway,PI3k/Akt signaling pathway,BDNF/TrkB signaling pathway and ERK/MAPK signaling pathway.It provides a relevant reference for future research on ischemic stroke-specific drugs and new clinical treatment methods.

BACKGROUND:The aging of mesenchymal stem cells is one of the main causes of aging-related diseases,and seriously affects its clinical application.Traditional Chinese medicine has a good anti-aging effect,and it can inhibit the aging of mesenchymal stem cells to promote its application in tissue engineering and prevent and treat aging-related diseases. OBJECTIVE:To review the effect and mechanism of traditional Chinese medicine on inhibiting the aging of mesenchymal stem cells. METHODS:We searched CNKI and PubMed for the literature on inhibiting mesenchymal stem cell aging with traditional Chinese medicine from 2012 to 2022.The keywords were"traditional Chinese medicine,mesenchymal stem cells(MSCs),aging"in Chinese and English,respectively.Finally,92 articles were included for further review. RESULTS AND CONCLUSION:(1)We summarized five main mechanisms of the aging of mesenchymal stem cells:DNA damage,telomere shortening,oxidative stress,autophagy disorder and mitochondrial dysfunction.(2)This paper reviewed the phenotypic characteristics of senescent mesenchymal stem cells,including increases in cell volume,decreases in proliferation and multi-directional differentiation,increases in β-galactosidase activity,and activation of p21 and p16 pathways,and so on.(3)We summarized the main mechanisms of Chinese medicine inhibiting the senescence of mesenchymal stem cells at present,including inhibiting the activation of the Wnt pathway,inhibiting the production of mitochondrial reactive oxygen species,promoting the silencing of information regulator factor 2 homolog 1,phosphatidylinositol 3-kinase/protein kinase B,adenosine 5'-monophosphate-activated protein kinase and nuclear factor E2 related factor 2 pathway activation,and promoting the expression of telomerase reverse transcriptase.(4)At present,bone marrow mesenchymal stem cells are the most widely studied in the research of traditional Chinese medicine to inhibit the aging of bone marrow mesenchymal stem cells,and the effect is better.(5)Zuogui Wan,Bushen Tiaogan Formula,resveratrol,Astragalus membranaceus and other traditional Chinese medicines can prevent and treat osteoporosis by promoting the proliferation and osteogenic differentiation of aging mesenchymal stem cells.However,the mechanism of Chinese medicine in improving the paracrine function of mesenchymal stem cells and preventing other aging-related diseases by inhibiting the aging of mesenchymal stem cells needs to be further explored.

Parkinson's disease （PD） is a common neurological degenerative disease in the middle-aged and elderly， characterized by pathological changes of progressive degeneration of dopaminergic neurons in the substantia nigra and Lewy body formation， with high prevalence and long course of disease. The drug is mainly used to treat PD in western medicine， and the early curative effect is remarkable. However， with the progression of the disease and the long-term use of the drug， the efficacy will be significantly reduced， or there may be sports complications， and the long-term efficacy is not good. As a traditional medical system， traditional Chinese medicine has a unique understanding of PD. Traditional Chinese medicine plays an important role in the treatment of PD， which is natural， mild， safe， and effective， and it can cooperate with western medicine to enhance its efficacy and reduce the adverse reactions of western medicine. The pathogenesis of PD is complex， involving multiple levels such as mitochondrial dysfunction and apoptosis. Neuroinflammation is also involved in the progressive degeneration of dopaminergic neurons in PD. The Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway is a classic inflammatory pathway， and its expression changes play an important role in the occurrence and development of inflammatory response in the body. In recent years， the research on this pathway in TCM is increasing. This paper summarized the literature of traditional Chinese and western medicine in the past 10 years and reviewed the relevant mechanism of TCM regulation of TLR4/NF-κB pathway in the treatment of PD from the aspects of TCM monomer， compound， and other TCM therapies， so as to provide some references for the search for new targets of drug therapy and gene therapy and the in-depth study of TCM prevention and treatment of PD.