Ischemic stroke is a cerebrovascular disease with high incidence and disability rates. Non-coding RNAs， as important regulatory factors for gene expression， play a key role in the development and progression of ischemic stroke， but their specific mechanisms of action remain unclear. This article systematically reviews the expression characteristics and regulatory roles of microRNAs， long non-coding RNAs， and circular RNAs in ischemic stroke and reveals the pathophysiological mechanisms of non-coding RNAs in ischemic injury by regulating the processes of cell apoptosis and autophagy， inflammatory response， blood-brain barrier integrity， and neuroregeneration. In addition， non-coding RNAs have shown the potential as biomarkers for the prediction， diagnosis， and prognostic evaluation of ischemic stroke. This article also analyzes the limitations of current research and proposes future research directions， so as to provide a theoretical foundation for exploring the mechanism of action of non-coding RNAs in ischemic stroke and developing innovative diagnostic and therapeutic strategies.
Review

Ischemic stroke(IS)is a disease caused by insufficient blood and oxygen supply to cerebral vessels,with the main clinical manifestations of hemiplegia,sensory disturbance,aphasia,and ataxia.Studies have shown that hypoxia-inducible factor 1α(HIF-1α),as the core regulatory element of oxygen homeostasis,can be rapidly activated under hypoxia/ischemia conditions,thereby playing an important role in the pathophysiology of IS.In recent years,more and more articles have shown that the active components of tradi-tional Chinese medicine,Chinese patent drugs,and compound traditional Chinese medicine prescriptions can effectively regulate the HIF-1α-related signaling pathway in the treatment of IS,but there is no systematic summary on regulation of the HIF-1α signaling pathway in the treatment of IS.Therefore,this article mainly summarizes the structure and physiological activity of HIF-1α and its mechanisms of action in IS and reviews related studies on Chinese medicine monomers and compound prescriptions in the treatment of IS in the past five years in China and globally.It is pointed out that the Chinese medicine monomers and compound prescriptions can repair brain tissue,alleviate brain tissue damage,and exert a therapeutic effect on IS by regulating the HIF-1α pathway to promote an-giogenesis,inhibit neuroinflammation and oxidative stress,promote energy metabolism,and repair blood-brain barrier damage.

Ischemic stroke(IS)is a common cerebrovascular disease,and its pathogenesis is closely associated with brain cell death due to insufficiency of cerebral blood supply.In recent years,cell apoptosis has become a research hotspot in the pathogenesis of IS.The B-cell lymphoma-2(Bcl-2)family proteins associated with cell apoptosis are the key regulators for apoptosis and are mainly in-volved in the intrinsic apoptotic pathway,and they regulate cell apoptosis by mediating the two pathways of mitochondrial membrane permeability and Ca2? overload,thereby delaying the progression of IS.Starting from the anti-apoptotic mechanisms of Bcl-2 family proteins,this article summarizes the research advances in traditional Chinese medicine for the prevention and treatment of IS by regu-lating B-cell lymphoma-2 family proteins from the aspects of the structural features of Bcl-2 family proteins,their anti-apoptotic role in IS,and traditional Chinese medicine regulation.The results show that the anti-apoptotic strategies in IS mainly focus on the regula-tion of Bcl-2 and Bax proteins,and monomers of Chinese herbs,traditional Chinese medicine extracts,and compound traditional Chi-nese medicine prescriptions were used for treatment,which further confirms the great potential of traditional Chinese medicine in the prevention and treatment of IS and provides a theoretical basis for future experimental research and clinical treatment.

Currently,the global incidence rate of ulcerative colitis(UC)is increasing year by year.Conventional therapies cannot ef-fectively repair damaged tissue and reconstruct immune homeostasis,with a clinical remission rate of<50%,and most of the patients are facing problems such as drug resistance,irreversible damage to the mucosal barrier,and fibrosis,which require novel therapeutic methods.Recent studies have shown that bone marrow mesenchymal stem cells(BMSCs),with the help of their characteristics of multi-potential differentiation and inflammatory chemotaxis,can precisely modulate the microenvironment by secreting anti-inflammatory mediators and immunomodulatory proteins and significantly promote the regeneration and functional recovery of colonic mucosa.Based on these findings,BMSCs have become an important research direction in the field of UC treatment.Therefore,this article integrates ex-isting therapeutic systems and systematically analyzes the therapeutic mechanism of BMSCs,in order to provide a new theoretical basis and clinical guidance for the treatment of UC.

Objective To study the protective effects and mechanism of sacubitril(Sac)/valsartan(Val)on cardiomyocytes of rabbits with heart failure induced by doxorubicin(DOX).Methods Thirty New Zealand rabbits were selected to establish DOX-induced heart failure rabbit model.Twenty-five rabbits with successful modeling were randomly assigned to model group(DOX group,n=9),DOX+Val group(n=8),and DOX+Sac/Val group(n=8);and another 8 New Zealand rabbits were selected as blank group.The DOX+Val group was gavaged with 4.65 mg/kg Val suspension each time,the DOX+Sac/Val group was gavaged with 9.3 mg/kg Sac/Val suspension each time,and the blank group and DOX group were gavaged with equal volume of distilled water each time.Each group was gavaged twice a day for 8 weeks.After 8 weeks of administration,echocardiography was used to measure left ventricular end-diastolic diameter(LVDD),left ventricular end-systolic diameter(LVSD),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS).The heart mass index(HMI)and left ventricular mass index(LVMI)were calculated.The pathological morphology and myocardial fibrosis of myocardial tissue were observed by hematoxylin-eosin(H-E)and Masson staining.The ultrastructure of cardiomyocytes was observed by transmission electron microscope.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining was used to observe cardiomyocytes apoptosis and apoptosis rate was calculated.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),high-sensitivity cardiac troponin I(Hs-cTNI),angiotensin Ⅱ(Ang Ⅱ),aldosterone(ALD),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),cyclic guanosine monophosphate(cGMP),and protein kinase G(PKG)in serum.Quantitative polymerase chain reaction(qPCR)was used to detect the expression of natriuretic peptide receptor A(NPR-A),cGMP-specific phosphodiesterase 5A(PDE5A[cGMP]),PKG,B-cell lymphoma 2(Bcl-2),Bcl-2 associated X protein(Bax),and cysteine aspartate protease 3(caspase 3)mRNA in myocardial tissue.Western blotting was used to detect the expression of phosphorylated cAMP response element-binding protein(p-CREB),phosphorylated Bcl-2 related death promoting factor(p-Bad),Bcl-2,Bax,and caspase 3 proteins in myocardial tissue.Results Compared with the blank group,the LVDD and LVSD in the DOX group were increased(both P<0.01),the LVEF and LVFS were decreased(both P<0.01)and the HMI and LVMI were increased(both P<0.01);the apoptosis and apoptosis rate of cardiomyocytes were increased(P<0.01);the levels of NT-proBNP,Hs-cTNI,Ang Ⅱ,ALD,ANP,BNP,cGMP and PKG and the expression of NPR-A,PDE5A(cGMP),PKG,p-CREB,Bax and caspase 3 were all increased(all P<0.01),while the expression of Bcl-2 was decreased(P<0.01),and the expression of p-Bad had no significant difference(P>0.05).Compared with the DOX group,the LVDD and LVSD of the DOX+Sac/Val group and DOX+Val group were decreased(all P<0.01),the LVEF and LVFS were increased(all P<0.01)and the HMI and the LVMI were decreased(all P<0.01);the apoptosis and apoptosis rate of cardiomyocytes were decreased(all P<0.01);the levels of NT-proBNP,Hs-cTNI,Ang Ⅱ,ALD,ANP,BNP,cGMP and PKG and the expression of NPR-A,PDE5A(cGMP),PKG,Bax and caspase 3 were all decreased(all P<0.01),while the expression of Bcl-2 was increased(P<0.01);and the expression of p-CREB and p-Bad was increased in the DOX+Sac/Val group(both P<0.01),but there was no significant difference in the DOX+Val group(both P>0.05).Compared with the DOX+Val group,the DOX+Sac/Val group showed a decrease in all indicators except for LVEF,LVFS,NPR-A,ANP,BNP,cGMP,PDE5A(cGMP),PKG,p-CREB,p-Bad,and Bcl-2,which were all elevated(all P<0.05).Myocardial pathology and transmission electron microscopy showed that Sac/Val effectively protected cardiomyocytes,reduced cardiomyocytes apoptosis and myocardial fibrosis,and these effects were significantly better than those of Val.Conclusion Sac/Val can effectively reduce cardiomyocytes apoptosis,improve cardiac function and reduce myocardial fibrosis in rabbits with heart failure,and these effects are superior to Val.Its mechanism may be related to activating the NPR-A/cGMP/PKG signaling pathway and inhibiting renin-angiotensin-aldosterone system.

Objective:To investigate the effects of Zhibai Dihuang Pills on neurons of cognitive dysfunction in D-galactose (D-gal) model mice.Methods:Totally 60 male mice were divided into four groups using a random number table method: control group, model group, donepezil group, and Zhibai Dihuang Pills group, with 15 mice in each group. Except for the control group, the other groups were subcutaneously injected with D-galactose solution at a dosage of 125 mg/kg once a day for 8 weeks to prepare the aging model. Mice in the donepezil group were intragastrically administered donepezil solution at a dosage of 0.65 mg/kg, and those in the Zhibai Dihuang Pills group were intragastrically administered Zhibai Dihuang Pills solution at a dosage of 1.56 g/kg. The control group was intragastrically administered an equal volume of physiological saline once a day for 8 weeks. The object recognition test and Morris Water Maze were used to assess object recognition memory and spatial learning memory abilities of mice in each group, respectively. Hematoxylin-Eosin (HE) staining and Nissl staining were employed to observe the morphology of neurons in the hippocampal region; Golgi staining was used to observe neuronal dendritic spines; Western Blot was used to detect the protein expression levels of PI3K, p-Akt/Akt, glycogen synthase kinase 3β (GSK3β), postsynaptic density protein-95 (PSD-95), and synaptophysin (SYP) in the hippocampus region; RT-qPCR was performed to detect mRNA expression of PI3K, Akt and GSK3β in the hippocampus region.Results:Compared with the model group, the recognition index in both the donepezil group and the Zhibai Dihuang Pills group increased ( P<0.05), the escape latency was shortened ( P<0.05), the platform crossings times and the target quadrant dwell time increased ( P<0.05), the number of nerve cells in the hippocampal region increased, arranged closely, the number of Nissl bodies increased, the morphology returned to normal, and the density of dendritic spines increased; the protein expressions of PI3K, PSD-95, and SYP in the hippocampal region and the ratio of p-Akt/Akt increased ( P<0.01), the mRNA level of PI3K increased ( P<0.01 or P<0.05), and the protein and mRNA levels of GSK3β decreased ( P<0.01 or P<0.05). Conclusion:Zhibai Dihuang Pills can improve the learning and memory ability and rescue neuronal damage in D-gal model mice, and the mechanism may be related to the activation of PI3K/Akt pathway and the restoration of synaptic connections.

Objective:To observe the effects of electroacupuncture at "Shenting", "Benshen" and "Baihui" acupoints on the mechanical pain threshold and JAK/PI3K/TRPV1 pathway in the trigeminal ganglion of rats with trigeminal neuralgia model; To explore the related mechanism.Methods:Totally 36 male SD rats were divided into sham-operation group, model group and electroacupuncture group using random number table method, with 12 rats in each group. Except for the sham-operation group, rats in the model group and electroacupuncture group were modeled by infraorbital nerve chronic constriction injury. In the electroacupuncture group, electroacupuncture was performed at "Shenting", "Benshen" and "Baihui" 14 days after surgery, 20 min every day, once every other day, and every 3 times for 1 course of treatment with an interval of 2 d between each course of treatment. A total of 2 courses of treatment were performed. VonFrey fiber wire was used to measure the mechanical pain threshold of rat whisker pads. HE staining was used to observe the morphology and structure of trigeminal ganglion of rats in each group. Immunohistochemistry and Western blot method were used to observe the protein expressions of JAK, PI3K and TRPV1 in trigeminal ganglion of rats, and the serum level of IL-6 was detected in the serum of rats by ELISA.Results:Compared with the model group, the pain threshold of the electroacupuncture group increased significantly ( P<0.05), and the infiltration of inflammatory cells and demyelination in the trigeminal nerve ganglion decreased, and the positive expressions of JAK, PI3K, and TRPV1 in the trigeminal ganglion decreased ( P<0.05 or P<0.01), the protein expressions of JAK2, PI3K, and TRPV1 decreased ( P<0.05 or P<0.01), and the serum IL-6 level decreased ( P<0.01). Conclusions:Electroacupuncture at "Shenting", "Benshen" and "Baihui" may play an analgesic role by regulating IL-6 levels and inhibiting the activation of JAK/PI3K/TRPV1 signaling pathway.

Objective:To explore the mechanism of Amomi Fructus in ameliorating ethanol-induced gastric ulcer (GU) in mice using metabolomics, network pharmacology and molecular docking techniques.Methods:The mice were divided into the blank group, model group, aqueous extract of Amomi Fructus group, volatile oil of Amomi Fructus group, combined aqueous extract and volatile oil of Amomi Fructus group and omeprazole group according to the random number table method, with 10 mice in each group. The blank and model groups were gavaged with sodium carboxymethyl cellulose, the Amomi Fructusaqueous extract group was gavaged with 0.152 5 g/kg of Amomi Fructus aqueous extract, the Amomi Fructus volatile oil group was gavaged with 26 μl/kg of Amomi Fructus volatile oil, the Amomi Fructus aqueous extract and volatile oil combined group was gavaged with 0.152 5 g/kg+26 μl/kg of Amomi Fructus aqueous extract and volatile oil synergistic solution, and the omeprazole group was gavaged with 5.2 mg/kg of omeprazole, 1 time/day, which was administered continuously for 7 d. The gastric ulcer model was established by using ethanol 2 h after the last administration, and the pathological changes of gastric histology were observed by using HE staining; the main differential metabolites were detected by UPLC-Q-TOF-MS/MS non-targeted metabolomics technique, and the metabolic pathway enrichment analysis was carried out; the potential targets and key pathways of the anti-GU action of Amomi Fructus were predicted by network pharmacology; the "metabolite-response-enzyme-gene" network was established by combining the serum metabolomics and network pharmacology; and the key targets were verified by molecular docking technology.Results:HE staining showed that the gastric mucosa of mice in the model group was severely damaged, with cellular tissue damage and inflammatory cell infiltration, whereas the drug administration group showed some protective effects; the results of non-targeted metabolomics showed that 2 metabolites were up-regulated and 17 metabolites were down-regulated in sera of mice in the co-administration group of aqueous extract and volatile oil of Amomi Fructus compared with the control group, and the 19 metabolites were strongly correlated and well clustered, involving nicotinic acid and nicotinamide metabolism, citric acid cycle, glyoxylate and dicarboxylic acid metabolism, phenylalanine metabolism, alanine, aspartate and glutamate metabolism and other metabolic pathways; the results of network pharmacology showed that Amomi Fructus improved GU by affecting target proteins, such as STAT3, AKT1, SRC, and TLR4, which were closely linked to the signaling pathways of cancer pathway, human cytomegalovirus infection, and lipids and atherosclerosis; the joint analysis of network pharmacology and the combined analysis of network pharmacology and metabolomics identified the glycerophospholipid metabolic pathway as the main metabolic pathway in which Amomi Fructus may exert gastroprotective effects; the molecular docking results showed that the main active component of quercetin had a better binding ability to the key targets.Conclusion:Amomi Fructus exerts a protective effect on ethanol induced GU model by regulating the glycerophospholipid metabolism pathway, providing theoretical basis for further research on Amomi Fructus.

Objective:To investigate the anti-inflammatory effects of Duhuo Jisheng Decoction on type Ⅱ collagen emulsion induced arthritis (CIA) model rats from the perspective of M1/M2 macrophage balance mediated development of rheumatoid arthritis.Methods:SD rats were divided into a normal group of 8 and a model group of 32. The CIA model was established using collagen antibody induction method for modeling. The successfully modeled rats were randomly divided into model group, methotrexate group, and Duhuo Jisheng Decoction medium- and high-dosage groups using a random number table method, with 8 rats in each group. Duhuo Jisheng Decoction medium- and high-dosage groups were orally administered with Duhuo Jisheng Decoction at dosages of 13.5 and 27.0 g/kg, once a day; methotrexate group received oral administration of 2.0 mg/kg methotrexate twice a week; normal group and model group were given equal volumes of physiological saline by gavage once a day for 28 consecutive days. The general condition of each group of rats was observed, the degree of swelling in the right knee joint was measured, and the arthritis index was scored; HE was used to observe pathological changes in synovial tissue; immunofluorescence was used to detect the expressions of markers CD86 and CD206 in synovial macrophages; Real time PCR was used to detect the mRNA levels of IL-6, TNF-α, IL-10, and TGF-β in synovial tissue.Results:Duhuo Jisheng Decoction could significantly improve the mental state of the rats and reduced the swelling of the knee joints and the arthritis index ( P<0.01). Compared with the model group, the cartilage structure in the knees of rats in the Duhuo Jisheng Decoction group was more intact and clearer. The expression level of the M1 macrophage marker CD86 significantly decreased, and the expression level of the M2 macrophage marker CD206 significantly increased; the mRNA expressions of IL-6 and TNF-α in the knee joint synovial tissue were significantly reduced ( P<0.05), while IL-10 and TGF-β levels significantly increased ( P<0.05). Conclusion:Duhuo Jisheng Decoction may promote macrophage polarization towards M2 type, thereby achieving M1/M2 macrophage balance, alleviating inflammatory response in rheumatoid arthritis rats, and exerting therapeutic effects on rheumatoid arthritis.

Objective:To explore the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia using network pharmacology; To verify the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia through animal experiments.Methods:The active components and potential targets of Shiwei Chaihu Shugan Powder were searched in TCMSP and Uniprot databases. Breast hyperplasia genes were searched in GeneCards and OMIM databases. The intersection targets were obtained by online tool Venny, and the "drug-component-target" network was constructed by Cytoscape 3.8.2 software. The protein interaction (PPI) network was constructed using the String platform, and GO function and KEGG pathway enrichment analysis were performed using the DAVID annotation database. Molecular docking was performed using PDB, PubChem database, PyMOL 2.1 and AutoDockvina 1.2.5 software to predict the biological mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia. Rats were divided into blank group, model group, tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups according to the random number table method, with 6 rats in each group. Except for the blank group, the other groups were prepared with the modified estrogen-progesterone-induced rat mammary hyperplasia model. Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups were intragastrically administered with Shiwei Chaihu Shugan Powder solution at 7.425 g/kg, 14.850 g/kg, and 29.700 g/kg respectively, while the tamoxifen group was intragastrically administered with 2.1 mg/kg tamoxifen. The blank group and the model group were intragastrically administered with the same volume of drinking water, once a day, for consecutive 28 d. The thickness of the mammary gland was measured by small animal ultrasound. The height and width of the nipples were measured by vernier calipers. The levels of serum E2 and P were detected by ELISA. The morphology of mammary tissue was observed by HE staining. The expressions of ERα, ERβ, SRC-1 and CBP/p300 proteins were detected by Western blot.Results:A total of 92 active components and 274 disease-drug intersection targets were screened out. GO functional enrichment analysis showed that Shiwei Chaihu Shugan Powder was closely related to positive regulation of gene expression, positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, negative regulation of apoptosis process, response to heterogeneous stimulation, and regulation of hormone levels. KEGG enrichment analysis showed that the core targets might be related to NF-κB signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, PI3K/Akt signaling pathway, and regulating hormone levels. Molecular docking results showed that the core components had a good binding energy with the core target and a stable conformation. Compared with the model group, the thickness of the mammary gland in the tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups decreased ( P<0.01), the serum P level increased ( P<0.05), the expressions of ERα, SRC-1, and CBP/p300 proteins decreased ( P<0.01), and the expression of ERβ protein increased ( P<0.01); the height of the nipples in the Shiwei Chaihu Shugan Powder medium- and high-dosage groups and the tamoxifen group decreased ( P<0.01), and the serum E2 level increased ( P<0.05). Conclusion:Shiwei Chaihu Shugan Powder may play a role in the treatment of breast hyperplasia by regulating the levels of estrogen and related proteins.