In the central nervous system (CNS), the myelin sheath, a specialized membrane structure that wraps around axons, is formed by oligodendrocytes through a highly coordinated spatiotemporal developmental program. The process begins with the directed differentiation of neural precursor cells into oligodendrocyte precursor cells (OPCs), followed by their migration, proliferation, differentiation, and maturation, ultimately leading to the formation of a multi-segmental myelin sheath structure. Recent single-cell sequencing research has revealed that this process involves the temporal regulation of over 200 key genes, with a regulatory network composed of transcription factors such as Sox10 and Olig2 playing a central role. The primary function of the myelin sheath is to accelerate nerve signal transmission and protect nerve fibers from damage. Its insulating properties not only increase nerve conduction speed by 50-100 times but also ensure the long-term functional integrity of the nervous system by maintaining axonal metabolic homeostasis and providing mechanical protection. The pathological effects of myelin sheath injury exhibit a cascade amplification pattern: acute demyelination leads to action potential conduction block, while chronic lesions may cause axonal damage and neuronal death in severe or long-term cases, ultimately resulting in irreversible neurological dysfunction with neurodegenerative characteristics. Multiple sclerosis (MS) is a neurodegenerative disease characterized by chronic inflammatory demyelination of the CNS. Clinically, the distribution of lesions in MS exhibits spatial heterogeneity, which is closely related to differences in the regenerative capacity of oligodendrocytes within the local microenvironment. Emerging evidence suggests that astrocytes form a dynamic “neural-immune-metabolic interface” and play a multidimensional regulatory role in myelin development and regeneration by forming heterogeneous populations composed of different subtypes. During embryonic development, astrocytes induce the targeted differentiation of OPCs in the ventricular region through the Wnt/β-catenin pathway. In the mature stage, they secrete platelet-derived growth factor AA (PDGF-AA) to establish a chemical gradient that guides the precise migration of OPCs along axonal bundles. Notably, astrocytes also provide crucial metabolic support by supplying energy substrates for high-energy myelin formation through the lactate shuttle mechanism. In addition, astrocytes play a dual role in myelin regulation. During the acute injury phase, reactive astrocytes establish a triple defense system within 72 h: upregulating glial fibrillary acidic protein (GFAP) to form scars that isolate lesions, activating the JAK-STAT3 regeneration pathway in oligodendrocytes via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

Objective To investigate the influences of Lycium barbarum polysaccharide on apoptosis of corneal epithelial cells induced by hypertonicity through regulating adenosine monophosphate activated protein kinase(AMPK)/uncoordinated 51-like kinase 1(ULK1)autophagy pathway.Methods The ophthalmoxerosis cell model was established by osmotic pressure of 500 mOsm·L-1 on corneal epithelial cells.They were divided into model group,positive control group(0.3％sodium hyaluronate eye drops),inhibitor group(1 mg·mL-1 Lycium barbarum polysaccharide+10 μmol·L-1compound C),experimental-L,-H groups(0.5,1.0 mg·mL 1 Lycium barbarum polysaccharide),and normal cultured CRL-11135 cells were taken as blank group(no treatment was performed).Cell apoptosis was detected by flow cytometry.Autophagy was detected by MDC staining.Western blot was used to detect the expressions of p-AMPK/AMPK and p-ULK1/ULK1.Results The apoptosis rates of experimental-L,experimental-H,positive control,inhibitor,model and blank groups were(26.47±2.13)％,(13.68±2.21)％,(12.54±2.16)％,(18.73±2.12)％,(37.56±3.25)％and(6.35±2.14)％;the relative contents of autophagosomes were(59.63±8.14)％,(89.89±9.04)％,(90.31±9.13)％,(62.75±7.26)％,(43.11±6.45)％and(100.00±0.00)％;p-AMPK/AMPK were 0.45±0.07,0.64±0.08,0.66±0.06,0.53±0.04,0.34±0.05 and 0.87±0.06;p-ULKl/ULKl were 0.54±0.06,0.75±0.05,0.77±0.03,0.65±0.04,0.46±0.04 and 0.92±0.08,respectively.The above indexes in experimental-L,-H groups and positive control group were significantly different from those in model group(all P＜0.05);the above indexes in inhibitor group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Lycium barbarum polysaccharide can inhibit the apoptosis of corneal epithelial cells induced by hypertonicity by activating the AMPK/ULK1 autophagy pathway.

Objective To explore the anti-atherosclerosis mechanism of Hirudo and its effect on autophagy in mice.Methods Forty healthy male ApoE-/-mice were randomly divided into model group,control group(3 × 10-3 g·kg-1·d-1 simvastatin)and experimental-L,experimental-M,experimental-H groups(0.45,0.9,1.8 g·kg-1· d-1,Maixuekang capsule).Eight healthy male C57BL/6J mice were divided into blank group.The mice were fed with common diet for 1 week.Then,except blank group,other groups were fed with high-fat diet.After 8 weeks of modeling,the atherosclerosis(AS)mice were given drugs orally once a day for 12 weeks,and fed with high-fat diet in the meantime.The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)in serum were determined by enzyme-linked immunosorbent assay(ELISA).The levels of Beclin-1,LC3 autophagy protein were detected by Western blot method.Results The IL-6 contents in the experimental-H,experimental-M,experimental-L,control,model and blank groups were(107.59±3.03),(99.31±5.12),(103.52±2.28),(98.68±4.68),(112.66±6.08),(93.98±3.43)pg·mL-1;the TNF-α contents were(538.41±30.26),(504.49±21.51),(538.51±19.05),(494.05±25.08),(578.53±26.32),(467.35±21.53)pg·mL-1.For the above indexes,the differences between model group and experimental-H group,experimental-M group,experimental-L group,control group,blank group were all statistically significant(all P＜0.05).The Beclin-1 protein expression levels in the experimental-H,experimental-M,experimental-L,control and model groups were 1.48±0.05,1.72±0.05,1.19±0.02,1.51±0.04,0.66±0.03;the LC3 Ⅱ protein expression levels were 1.53±0.01,1.83±0.02,1.16±0.01,1.90±0.01,0.49±0.01,and the differences between model group and experimental-H group,experimental-M group,experimental-L group,control group were all statistically significant(all P＜0.05).Conclusion Hirudo can significantly reduce the area of atherosclerotic plaque by regulating the level of autophagy.

Objective To investigate the effect of isoliquiritigenin on airway inflammation mice with neutrophil asthma and its possible mechanism.Methods Neutrophil asthma mouse model were established using ovalbumin.Balb/c mice were randomly divided into control group(equal amounts of 0.9％NaCl were given),model group(ovalbumin modeling),DXM group(intraperitoneal injection of 4 mg·kg-1 dexamethasone),experimental-L,-H groups(intraperitoneal injection of 100,200 mg·kg-1 isoliquiritigenin),with 11 mice in each group.Airway resistance of each group of mice was detected within 24 h after the last atomization excitation,and lung tissue and bronchoalveolar lavage fluid were taken;the total cell count was performed by cell counting plate;the cell classification count was performed by Richs-giemsa staining;the levels of inflammatory factors in bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay;Weatern blot assay was used to detect protein expression in lung tissue.Results The airway resistance values of control group,model group,DXM group,experimental-L group and experimental-H group were(0.84±0.08),(3.34±0.34),(1.23±0.15),(2.47±0.19)and(1.54±0.18)cmH2 O·s-1;the total number of white blood cells were(15.03±0.11),(331.20±26.64),(38.73±3.28),(180.35±16.89)and(82.74±10.51)x 104·mL-1;interleukin 17(IL-17)levels were(4.79±0.58),(19.21±2.39),(6.35±0.81),(15.96±1.10)and(9.04±0.65)pg·mL-1;V-set and immunoglobulin domain-containing 4(VSIG4)protein expression levels were 0.67±0.04,0.24±0.04,0.59±0.06,0.37±0.04 and 0.53±0.05;Nod-like receptor family heat protein domain associated protein 3(NLRP3)protein expression levels were 0.24±0.02,0.74±0.07,0.35±0.04,0.65±0.08 and 0.44±0.03,respectively.The above indexes were compared between the model group and the control group,and the above indexes of DXM,experimental-L and experimental-H groups were compared with model group,and the differences were statistically significant(all P＜0.05).Conclusion Isoliquiritigenin may regulate the VSIG4/NLRP3 complex inflammatory pathway,reduce airway resistance,inhibit the release of inflammatory mediators and improve airway inflammation in mice with neutrophil asthma.

Objective To investigate the inhibitory effect of quercetin on Gastro entero pancreatic NEN(GEP-NEN).Methods Human pancreatic neuroendocrine tumor BON-1 cells were randomly divided into control group,quercetin group(80 μmol·L-1 quercetin),quercetin+si-NC group(transfected with si-NC+80 μmol·L-1 quercetin),quercetin+si-growth arrest-specific+ranscript 5(GAS5)group(transfected with si-GAS5+80 μmol·L-1 quercetin).Dual luciferase reporter gene assay was used to verify the targeted binding of GASS5 to miR-18b-5p;real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the mRNA expression levels of B-cell lymphoma-2(Bcl-2)and Bel-2 associated X protein(Bax);positive expression of GAS5 and miR-18b-5p in cells was detected by fluorescence in situ hybridization(FISH)assay.Results Dual luciferase reporter gene results showed that GAS5 was targeted to miR-18b-5p.The GAS5 expression levels of control group,quercetin group,quercetin+si-NC group and quercetin+si-GAS5 group were 1.00±0.13,1.72±0.19,1.78±0.14 and 1.16±0.11,respectively;the expression levels of miR-18b-5p were 1.00±0.15,0.67±0.08,0.72±0.06 and 0.95±0.11 respectively;Bax mRNA expression levels were 1.00±0.12,2.17±0.25,2.32±0.28 and 1.37±0.15,respectively;Bcl-2 mRNA expression levels were 1.00±0.15,0.41±0.05,0.37±0.06 and 1.21±0.13,respectively.The above indexes were significantly different between quercetin group and control group(all P＜0.05);the above indexes were significantly different between quercetin+si-NC group and quercetin+si-GAS5 group(all P＜0.05).Conclusion Quercetin may slow down the development of GEP-NEN by targeting GAS5/miR-18b-5p molecular axis to inhibit cell growth.

Objective To explore the effects of long non-coding RNA(lncRNA)HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease(NAFLD).Methods Wild-type C57BL/6(WT)mice and myeloid cell-specific HEM2M knock-in(MYKI)mice were fed normal(ND)or high-fat diet(HFD)for 12 weeks.After intraperitoneal glucose tolerance and insulin tolerance tests,the mice were euthanized for detection of liver function indicators in the serum and liver tissue.HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies,and the levels of IL-6,IL-1β,and TNF-α in the liver tissues were determined with ELISA.The mRNA expressions of HEM2M and the markers of M1 macrophages(TNF-α,iNOS,and IL-6)and M2 macrophages(Arg-1,YM-1,and IL-10)were detected using qRT-PCR,and the protein expressions of P-AKT,T-AKT,NLRC4,caspase-1 and GSDMD were assayed using immunoblotting.Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay.Results Compared with HFD-fed WT mice,MYKI mice with HFD feeding showed milder liver function damage(P<0.01),alleviated hepatic steatosis,and reduced liver macrophage infiltration,glucose tolerance impairment and insulin resistance(P<0.01).The levels of IL-6,IL-1β,and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased(P<0.01)and those of M2 type markers increased(P<0.01)in the liver tissues of HFD-fed MYKI mice,which also showed reduced NLRC4 inflammasome activity,caspase-1 activation,and GSDMD-N protein expression compared with their WT counterparts(P<0.05).Conclusion Overexpression of HEM2M reduces the production of hepatic inflammatory factors,improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation,which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.

Objective To explore the effects of long non-coding RNA(lncRNA)HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease(NAFLD).Methods Wild-type C57BL/6(WT)mice and myeloid cell-specific HEM2M knock-in(MYKI)mice were fed normal(ND)or high-fat diet(HFD)for 12 weeks.After intraperitoneal glucose tolerance and insulin tolerance tests,the mice were euthanized for detection of liver function indicators in the serum and liver tissue.HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies,and the levels of IL-6,IL-1β,and TNF-α in the liver tissues were determined with ELISA.The mRNA expressions of HEM2M and the markers of M1 macrophages(TNF-α,iNOS,and IL-6)and M2 macrophages(Arg-1,YM-1,and IL-10)were detected using qRT-PCR,and the protein expressions of P-AKT,T-AKT,NLRC4,caspase-1 and GSDMD were assayed using immunoblotting.Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay.Results Compared with HFD-fed WT mice,MYKI mice with HFD feeding showed milder liver function damage(P<0.01),alleviated hepatic steatosis,and reduced liver macrophage infiltration,glucose tolerance impairment and insulin resistance(P<0.01).The levels of IL-6,IL-1β,and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased(P<0.01)and those of M2 type markers increased(P<0.01)in the liver tissues of HFD-fed MYKI mice,which also showed reduced NLRC4 inflammasome activity,caspase-1 activation,and GSDMD-N protein expression compared with their WT counterparts(P<0.05).Conclusion Overexpression of HEM2M reduces the production of hepatic inflammatory factors,improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation,which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

To explore the absorption mechanism of APS-Ⅱ in vivo by establishing M cell model. First, Astragalus polysaccharides (APS) was divided into two different molecular weight polysaccharides APS-I ( > 2 000 kDa) and APS-II (10 kDa) by ultrafiltration, and APS-II (10 kDa) was prepared and fluorescently labeled. Meanwhile, M cell model was constructed by Caco-2 cells and Raji cells. The M cell model was treated with transport inhibitors to explore the transport of APS-Ⅱ on M cells. The results show that FITC has been successfully labeled to the end of APS-Ⅱ, and the M cell model was successfully constructed, which found that APS-Ⅱ could be transported by M cells, and four transport inhibitors of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), genistein, dynasore and nocodazole indicated that APS-II may enter cells through clathrin and caveolin-mediated endocytosis.