BACKGROUND:Studies have shown that tea polyphenols have anti-inflammatory effects on multiple organs,but there are few studies on the effects of tea polyphenols on central nervous system inflammation caused by exercise fatigue.OBJECTIVE:To explore the central anti-inflammatory effect and mechanism of tea polyphenols in exercise fatigue.METHODS:7-week-old male Kunming mice were divided into quiet control group,fatigue model group,and tea polyphenols group.In the fatigue model group,mice were given exhaustive swimming at one time.In the tea polyphenols group,tea polyphenols were injected into abdominal cavity half an hour before exhaustive swimming.The exhaustive swimming time in mice of fatigue model group and tea polyphenols group was recorded.Samples were taken from mice in each group after two hours of exhaustive swimming.The changes of brain tissue morphology and structure in each group were observed by hematoxylin-eosin staining.Western blot assay or real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of inflammation-related factors,the activation of microglia,and the activation of STAT3/nuclear factor-κB p65 inflammatory pathway in the brain tissue of mice.Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors.RESULTS AND CONCLUSION:(1)Compared with the fatigue model group,the swimming exhaustion time of mice in the tea polyphenols group was significantly prolonged.(2)No abnormality was found in the hematoxylin-eosin staining results of brain tissues of mice in each group.(3)Compared with the quiet control group,the expression levels of inflammatory factors tumor necrosis factor α protein,interleukin-1β protein,M1 activated microglia marker-inducible nitric oxide synthase protein,nuclear factor-κB p65 protein and mRNA,and p-STAT3 protein and STAT3 mRNA in the fatigue model group were significantly increased,while the expression levels of anti-inflammatory factor interleukin-10 protein and M2 activated microglia marker-arginase 1 protein were significantly decreased.Compared with the fatigue model group,the inflammatory reaction,microglia types and signal molecules showed opposite obvious changes in the tea polyphenols group.(4)The expression levels of tumor necrosis factor α,interleukin 1β,interleukin-10 in peripheral plasma and brain tissue were consistent in mice of each group.(5)To sum up,exercise fatigue can trigger inflammatory reaction of nerve center,and tea polyphenols can alleviate this inflammatory reaction,and then enhance the fatigue resistance time of mice.The effects of exercise-induced fatigue and tea polyphenols on the inflammatory reaction in the brain may be completed through STAT3/nuclearfactor-κB p65 pathway.

BACKGROUND:The α7 nicotinic acetylcholine receptor is highly expressed in the cerebral cortex and hippocampus,and has been shown to play an important regulatory role in the pathological development of Alzheimer's disease,making it a potential therapeutic target for Alzheimer's disease.OBJECTIVE:To summarize the close relationship and interaction mechanism between α7 nicotinic acetylcholine receptor and Alzheimer's disease.METHODS:Retrieve relevant literature was searched in CNKI and PubMed databases using the search terms of"alpha7 nicotinic acetylcholine receptor,Alzheimer's disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist"in Chinese and English,respectively.The search time was from database inception to July 2024.According to the inclusion criteria,the search results were accepted or excluded,and ultimately 83 articles that met the criteria were included for review.RESULTS AND CONCLUSION:The α7 nicotinic acetylcholine receptor interacts with β-amyloid protein to reduce the neurotoxicity of β-amyloid protein,such as promoting synaptic plasticity and rapid transmission of cholinergic synapses in Alzheimer's disease,alleviating central nervous system inflammation induced by β-amyloid protein,resisting neuronal apoptosis,and thus having a protective effect on the brain of patients with Alzheimer's disease.The α7 nicotinic acetylcholine receptor has great potential as a therapeutic target for Alzheimer's disease,but there are still a series of issues that need to be addressed,such as desensitization of α7 nicotinic acetylcholine receptor,stability of moderate activity,and gene polymorphism.Screening for drugs with high specificity,safety and multi-target binding action centered on the α7 nicotinic acetylcholine receptor will be a future direction for the treatment of Alzheimer's disease.

BACKGROUND:Tumor microenvironment can participate in the occurrence and development of gastric cancer and promote chemotherapy resistance in various ways.Among them,the tumor microenvironment crosstalk mediated by exosomal miRNAs can induce matrix reprogramming,participate in tumor heterogeneity,and form a microenvironment conducive to tumor proliferation,migration,invasion,immune escape,and chemotherapy resistance.OBJECTIVE:To review the mechanism of action of exosomal miRNAs in the microenvironment of gastric cancer and its application in the diagnosis and prognosis assessment of gastric cancer in recent years.METHODS:"Exosomal miRNAs,gastric cancer,angiogenesis,apoptosis,proliferation,migration,autophagy,invasion,immune response,chemotherapy resistance,biomarker"for English search terms and"exosomal miRNAs,gastric cancer"for Chinese search terms were searched in PubMed and CNKI databases.The search period was from 2017 to 2024.After preliminary screening by reading the title and abstract,the articles with poor correlation and repeated content were excluded,and 77 articles were finally included for induction and discussion.RESULTS AND CONCLUSION:(1)Exosomes,as important carriers of intercellular information exchange,can carry a variety of information substances such as miRNA,and realize intercellular signal transmission through three ways:activation of cell surface receptors on target cells,fusion with the plasma membrane of recipient cells,and endocytosis.(2)Exosomal miRNAs play an important role in the progression of gastric cancer by regulating the proliferation,apoptosis,autophagy,angiogenesis,invasion and metastasis,immune response,and the formation of drug resistance of gastric cancer cells.(3)The interaction between miRNAs and target mRNA and its regulatory network are widely found in tumorigenesis and human cancer development.Different types of exosomal miRNAs have different effects on the regulation of apoptosis of gastric cancer cells,and the effects of different exosomal miRNAs on apoptosis related proteins and pathways of gastric cancer cells are screened.Rational use of its inducers or inhibitors can regulate the apoptosis level of gastric cancer cells.(4)Exosomal miRNAs of different cell origin play an important role in the establishment of tumor microenvironment,angiogenesis,immune response,and chemotherapy resistance by inducing M1-polarized macrophages to M2 type.(5)Exosomal miRNAs exist extensively and stably in blood and other body fluids,and their differential expression in patients with gastric cancer can be used as a basis for diagnosis,prognosis,and treatment of patients with gastric cancer.Currently,exosomal miRNAs widely studied as biomarkers include miR-379-5p,miR-590-5p,miR-29s,miR-21,etc.Among them,the sensitivity and specificity of miR-590-5p are 63.7％and 86％,respectively.The expression level of miR-590-5p is closely related to the overall survival rate and the depth of invasion of gastric cancer patients.(6)The design of exosomal miRNAs mimics or inhibitors and their targeted delivery to the tumor site using nano-delivery vectors(such as exosomes and liposomes)to restore the normal level of miRNAs may be a new strategy for the treatment of gastric cancer.(7)Although exosomal miRNAs have great application prospects in the diagnosis and treatment of gastric cancer patients,there are still some problems to be solved.For example,the potential targets and mechanisms of exosomal miRNAs have not been fully explored,and their effectiveness and safety need to be further confirmed.The extraction and purification of exosomes lack standardized large-scale preparation processes.

BACKGROUND:Studies have shown that tea polyphenols have anti-inflammatory effects on multiple organs,but there are few studies on the effects of tea polyphenols on central nervous system inflammation caused by exercise fatigue.OBJECTIVE:To explore the central anti-inflammatory effect and mechanism of tea polyphenols in exercise fatigue.METHODS:7-week-old male Kunming mice were divided into quiet control group,fatigue model group,and tea polyphenols group.In the fatigue model group,mice were given exhaustive swimming at one time.In the tea polyphenols group,tea polyphenols were injected into abdominal cavity half an hour before exhaustive swimming.The exhaustive swimming time in mice of fatigue model group and tea polyphenols group was recorded.Samples were taken from mice in each group after two hours of exhaustive swimming.The changes of brain tissue morphology and structure in each group were observed by hematoxylin-eosin staining.Western blot assay or real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of inflammation-related factors,the activation of microglia,and the activation of STAT3/nuclear factor-κB p65 inflammatory pathway in the brain tissue of mice.Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors.RESULTS AND CONCLUSION:(1)Compared with the fatigue model group,the swimming exhaustion time of mice in the tea polyphenols group was significantly prolonged.(2)No abnormality was found in the hematoxylin-eosin staining results of brain tissues of mice in each group.(3)Compared with the quiet control group,the expression levels of inflammatory factors tumor necrosis factor α protein,interleukin-1β protein,M1 activated microglia marker-inducible nitric oxide synthase protein,nuclear factor-κB p65 protein and mRNA,and p-STAT3 protein and STAT3 mRNA in the fatigue model group were significantly increased,while the expression levels of anti-inflammatory factor interleukin-10 protein and M2 activated microglia marker-arginase 1 protein were significantly decreased.Compared with the fatigue model group,the inflammatory reaction,microglia types and signal molecules showed opposite obvious changes in the tea polyphenols group.(4)The expression levels of tumor necrosis factor α,interleukin 1β,interleukin-10 in peripheral plasma and brain tissue were consistent in mice of each group.(5)To sum up,exercise fatigue can trigger inflammatory reaction of nerve center,and tea polyphenols can alleviate this inflammatory reaction,and then enhance the fatigue resistance time of mice.The effects of exercise-induced fatigue and tea polyphenols on the inflammatory reaction in the brain may be completed through STAT3/nuclearfactor-κB p65 pathway.

BACKGROUND:Tumor microenvironment can participate in the occurrence and development of gastric cancer and promote chemotherapy resistance in various ways.Among them,the tumor microenvironment crosstalk mediated by exosomal miRNAs can induce matrix reprogramming,participate in tumor heterogeneity,and form a microenvironment conducive to tumor proliferation,migration,invasion,immune escape,and chemotherapy resistance.OBJECTIVE:To review the mechanism of action of exosomal miRNAs in the microenvironment of gastric cancer and its application in the diagnosis and prognosis assessment of gastric cancer in recent years.METHODS:"Exosomal miRNAs,gastric cancer,angiogenesis,apoptosis,proliferation,migration,autophagy,invasion,immune response,chemotherapy resistance,biomarker"for English search terms and"exosomal miRNAs,gastric cancer"for Chinese search terms were searched in PubMed and CNKI databases.The search period was from 2017 to 2024.After preliminary screening by reading the title and abstract,the articles with poor correlation and repeated content were excluded,and 77 articles were finally included for induction and discussion.RESULTS AND CONCLUSION:(1)Exosomes,as important carriers of intercellular information exchange,can carry a variety of information substances such as miRNA,and realize intercellular signal transmission through three ways:activation of cell surface receptors on target cells,fusion with the plasma membrane of recipient cells,and endocytosis.(2)Exosomal miRNAs play an important role in the progression of gastric cancer by regulating the proliferation,apoptosis,autophagy,angiogenesis,invasion and metastasis,immune response,and the formation of drug resistance of gastric cancer cells.(3)The interaction between miRNAs and target mRNA and its regulatory network are widely found in tumorigenesis and human cancer development.Different types of exosomal miRNAs have different effects on the regulation of apoptosis of gastric cancer cells,and the effects of different exosomal miRNAs on apoptosis related proteins and pathways of gastric cancer cells are screened.Rational use of its inducers or inhibitors can regulate the apoptosis level of gastric cancer cells.(4)Exosomal miRNAs of different cell origin play an important role in the establishment of tumor microenvironment,angiogenesis,immune response,and chemotherapy resistance by inducing M1-polarized macrophages to M2 type.(5)Exosomal miRNAs exist extensively and stably in blood and other body fluids,and their differential expression in patients with gastric cancer can be used as a basis for diagnosis,prognosis,and treatment of patients with gastric cancer.Currently,exosomal miRNAs widely studied as biomarkers include miR-379-5p,miR-590-5p,miR-29s,miR-21,etc.Among them,the sensitivity and specificity of miR-590-5p are 63.7％and 86％,respectively.The expression level of miR-590-5p is closely related to the overall survival rate and the depth of invasion of gastric cancer patients.(6)The design of exosomal miRNAs mimics or inhibitors and their targeted delivery to the tumor site using nano-delivery vectors(such as exosomes and liposomes)to restore the normal level of miRNAs may be a new strategy for the treatment of gastric cancer.(7)Although exosomal miRNAs have great application prospects in the diagnosis and treatment of gastric cancer patients,there are still some problems to be solved.For example,the potential targets and mechanisms of exosomal miRNAs have not been fully explored,and their effectiveness and safety need to be further confirmed.The extraction and purification of exosomes lack standardized large-scale preparation processes.

BACKGROUND:The α7 nicotinic acetylcholine receptor is highly expressed in the cerebral cortex and hippocampus,and has been shown to play an important regulatory role in the pathological development of Alzheimer's disease,making it a potential therapeutic target for Alzheimer's disease.OBJECTIVE:To summarize the close relationship and interaction mechanism between α7 nicotinic acetylcholine receptor and Alzheimer's disease.METHODS:Retrieve relevant literature was searched in CNKI and PubMed databases using the search terms of"alpha7 nicotinic acetylcholine receptor,Alzheimer's disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist"in Chinese and English,respectively.The search time was from database inception to July 2024.According to the inclusion criteria,the search results were accepted or excluded,and ultimately 83 articles that met the criteria were included for review.RESULTS AND CONCLUSION:The α7 nicotinic acetylcholine receptor interacts with β-amyloid protein to reduce the neurotoxicity of β-amyloid protein,such as promoting synaptic plasticity and rapid transmission of cholinergic synapses in Alzheimer's disease,alleviating central nervous system inflammation induced by β-amyloid protein,resisting neuronal apoptosis,and thus having a protective effect on the brain of patients with Alzheimer's disease.The α7 nicotinic acetylcholine receptor has great potential as a therapeutic target for Alzheimer's disease,but there are still a series of issues that need to be addressed,such as desensitization of α7 nicotinic acetylcholine receptor,stability of moderate activity,and gene polymorphism.Screening for drugs with high specificity,safety and multi-target binding action centered on the α7 nicotinic acetylcholine receptor will be a future direction for the treatment of Alzheimer's disease.

In western medicine， the small intestine anatomically belongs to the digestive system and is also an important immune organ of the body. The innate immune system of the small intestine consists of a tissue barrier， innate immune cells， and innate immune molecules. The dysfunction of any part can cause metabolic disorders and eventually lead to diabetes. In the pathogenesis of diabetes， traditional Chinese medicine （TCM） has the theory of ''spleen deficiency causing diabetes''， which points out that the impaired spleen function results in inadequate transformation， impaired essence spread， and turbidity by essence accumulation， which is the core pathological link of blood glucose metabolism disorder in diabetes. In terms of the relationship between the small intestine and the spleen， the theory of TCM holds that the small intestine is located in the abdomen and the abdomen is dominated by the spleen. The digestion， absorption， and endocrine functions of the small intestine are also similar to the functions of spleen in governing movement and transformation and spreading essence by virtue of spleen Qi. Therefore， the anatomical and physiological functions of the small intestine in western medicine are closely related to the spleen in TCM. At the same time， the spleen is closely related to the innate immune function of the small intestine in TCM. The spleen participates in the generation and distribution of defense Qi， and the process of defense Qi playing the external function is similar to the process of the activation of the innate immune response. The spleen is also an important organ involved in fluid metabolism， which can cooperate with the lung and kidney to timely remove turbid fluid from the body. It can also work with the stomach as the hub of Qi ascending and descending and regulate the physiological activities of "clear Yang" and "turbid Yin"， so as to ensure the homeostasis of the internal environment of the body， which is the basis for maintaining the normal function of the innate immunity of the small intestine. Therefore， taking "spleen deficiency causing diabetes" as a bridge， the theory of TCM and western medicine were combined to explain the relationship between small intestinal innate immunity imbalance and the pathogenesis of diabetes from the perspective of TCM， which is helpful to understand the pathogenesis of diabetes in a deeper level and also provide a new perspective and new way for the prevention and treatment of this disease with TCM.

Atherosclerosis （AS） is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries， and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress （ERS） is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment， while excessive ERS can cause unfolded protein reaction， activate inflammation， oxidative stress， apoptosis， autophagy， and other downstream pathways， and lead to cell damage， or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS， affects endothelial cells， smooth muscle cells， macrophages， endothelial progenitor cells， and other cell components closely related to its occurrence and development， influences the progress of AS by regulating cell function， and promotes the formation of AS plaque， the transformation of stable plaque to unstable plaque， and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS， and it is a research hotspot at present. Traditional Chinese medicine （TCM） believes that the origin of AS is the imbalance of Yin and Yang， the disharmony of Zangfu organs， and the abnormal operation of Qi， blood， and body fluid， which leads to the accumulation of phlegm， blood stasis， and other pathological products in the pulse channels， making the blood flow blocked or misfunction and causing the disease， which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex， and the symptoms are diverse， TCM has significant advantages in treating AS because of its multiple targets， multiple pathways， stable efficacy， strong individualization， and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer， Chinese herbal extract， Chinese herbal compound， and proprietary medicine， so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS.

BACKGROUND:The effect of electroacupuncture on the proliferation and differentiation of hippocampal oligodendrocytes in model mice with Alzheimer's disease remains poorly understood while demyelinating reaction related to oligodendrocytes is a common pathological reaction of Alzheimer's disease. OBJECTIVE:To investigate the effects and mechanism of electroacupuncture stimulation of"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)in Alzheimer's disease model mice on the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes. METHODS:Forty 6-week-old SPF APP/PS1 transgenic male Alzheimer's disease model mice were randomly divided into electroacupuncture group(n=20)and Alzheimer's disease model group(n=20).Healthy male C57BL/6J mice of the same age were used as normal controls(n=20).The mice in the electroacupuncture group received electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)for 16 weeks(20 minutes/day and one day off a week).After electroacupuncture,Morris water maze was used to detect the changes of learning and memory function.Immunohistochemistry was utilized to detect hippocampal dentate gyrus β-amyloid senile plaques.The expression of BrdU/NeuN and BrdU/GALC in the hippocampal dentate gyrus was detected by immunofluorescence double labeling.Western blot assay was used to detect the expression levels of neuron specific protein Nestin and oligodendrocyte specific protein GALC in the hippocampus.mRNA and protein levels of Notch1 and Hes1 in the hippocampus were detected by real-time fluorescence quantitative PCR and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the normal control group,the ability of learning and memory in the Alzheimer's disease model group decreased significantly;hippocampal dentate gyrus β-amyloid senile plaques increased significantly(P<0.01);the expression of GALC and Nestin in the hippocampus decreased significantly(P<0.01,P<0.05).(2)Compared with the Alzheimer's disease model group,the learning and memory ability of the electroacupuncture group was significantly increased;β-amyloid senile plaque in the hippocampal dentate gyrus decreased significantly(P<0.01).BrdU/NeuN double labeled positive cells in the hippocampal dentate gyrus and Nestin protein expression in the hippocampus increased significantly(P<0.01,P<0.05);GALC expression in hippocampus increased significantly(P<0.01).The mRNA and protein levels of Notch1 in the hippocampus were significantly increased(P<0.05,P<0.01).The mRNA and protein levels of Hes1 in the hippocampus decreased significantly(P<0.05).(3)These findings indicate that electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)of the Alzheimer's disease model infant mice can promote the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes,which may be regulated through the Notch1/Hes1 pathway.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.