Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P＜0.05,P＜0.01),while the expression of LC3-Ⅱ increased(P＜0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.

Aim To investigate the pharmacological effects of Danshenyin(DSY)in treating heart failure using network pharmacology and in vitro experiments.Methods Utilizing the Traditional Chinese Medicine Systems Pharmacology Analysis Platform(TCMSP),UniProt and other databases,active components and targets of DSY were analyzed.Disease-related targets were identified via searches in the Gene Cards and oth-er databases using keyword"heart failure".Subse-quently,the intersection of DSY and heart failure tar-gets was conducted to obtain core targets.The STRING database was employed to construct a protein-protein interaction(PPI)network,and biological function and signal pathway enrichment analysis were performed u-sing the DAVID database.Establish a network of"me-dicinal materials-ingredients-target-disease."Accord-ing to this network,a preliminary docking validation of the active ingredient with the target molecule.A mouse model of chronic heart failure was established through left anterior descending coronary artery ligation,with prediction results confirmed via echocardiographic de-tection and Western blotting.Results Network phar-macological analysis indicated that DSY may regulate the MAPK cascade signaling pathway via pharmacologi-cal components such as danshenyin aldehyde,luteolin,tanshinone A,and miltionone Ⅱ to treat heart failure.Animal experiments demonstrated significant improve-ments in ultrasound indexes like left ventricular cardiac function and outflow tract blood flow in the DSY treat-ment group compared to the model group(P＜0.05).Additionally,myocardial tissue phosphorylation levels of ERK,JNK,and p38 were significantly reduced(P＜0.05).Conclusion DSY protects the myocardi-um,influences the MAPK pathway,and holds promise for treating chronic heart failure.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Heart failure is the leading cause of mortality in cardiovascular diseases and represents the ultimate common manifestation of most cardiovascular conditions,impacting over 60 million individuals globally.Currently,heart transplantation remains the standard treatment for heart failure patients.Adherence to fundamental pharmacotherapy can improve quality of life and extend survival time for heart failure patients.However,due to the complex mechanism of heart failure and numerous complications,the limitations of conventional heart failure treatment strategies in clinical work are gradually magnified.In recent years,interventional therapy has emerged as an innovative approach for managing heart failure,attracting significant attention and achieving substantial breakthroughs that offer new hope for affected individuals.Injectable hydrogel has garnered considerable interest in biomedicine due to its minimally invasive nature and capacity for efficient therapeutic drug delivery.In the context of chronic heart failure,injectable hydrogel finds application primarily in tissue regeneration,drug delivery,and immunotherapy.This review mainly describes the application and research progress of injectable hydrogel in the treatment of heart failure.

Oromandibular dystonia (OMD) is a type of Meige syndrome, which is characterized by involuntary repeated abnormal postured contraction of bilateral masticatory muscles, orbicularis oris muscles and mimetic muscles. Involved nerves are buccal branch of facial nerve, mandibular marginal branch and/or mandibular branch of trigeminal nerve. At present, the pathogenesis of OMD is still unclear, and no specific treatment for OMD is noted. This article reviews the pathogenesis, clinical manifestations, classifications, diagnoses, differential diagnoses and treatments of oromandibular dystonia in order to strengthen the understanding of the disease.

Objective:To investigate the risk factors of cognitive dysfunction and its relationship with poor prognosis in elderly hypertensive patients with frailty.Methods:A total of 150 elderly hypertensive patients with frailty trea-ted in Eighth People's Hospital of Hebei Province from July 2019 to March 2021 were selected.According to pres-ence of cognitive dysfunction,they were divided into normal cognition group(n=92)and cognitive dysfunction group(n=58),and general data and prognosis condition were collected in two groups.Multivariate Logistic regres-sion analysis was used to analyze the risk factors of cognitive dysfunction in elderly hypertensive patients with frail-ty;Spearman correlation analysis was used to analyze the correlation between cognitive dysfunction degree and prog-nosis.Results:Compared with normal cognition group,cognitive dysfunction group was significantly older and pos-sessed significant higher proportions of diabetes,coronary heart disease,stroke,hyponatremia,multiple medication and malnutrition(P＜0.05 or＜0.01).Multivariate Logistic regression analysis indicated that age ≥75 years,stroke,multiple medication and malnutrition were independent risk factors for cognitive dysfunction in elderly hy-pertensive patients with frailty(OR=2.804～6.434,P＜0.05 or＜0.01).Incidence rate of poor prognosis events in cognitive dysfunction group was significantly higher than that of normal cognition group(51.72％vs.11.96％,P＜0.001).Spearman correlation analysis showed that cognitive dysfunction was significant positively correlated with poor prognosis in these patients(r=0.435,P＜0.001).Conclusion:Age,stroke,multiple medication and malnu-trition are independent risk factors for cognitive dysfunction in elderly hypertensive patients with frailty.Cognitive dysfunction is closely related to poor prognosis in these patients.

The complex chemical composition and limited research ideas of traditional Chinese medicine （TCM） have led to the unclear material basis and mechanism of the medicinal effects， which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study， we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore， a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM， thus promoting the modern research and the innovative development of TCM.

ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E₂ （PGE₂） in the mouse model， showcasing a significant inhibitory effect on the inflammatory pain caused by PGE₂. Nine components and 39 targets of saikosaponins， as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out， and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction （PPI） analysis showed that the main active components of Bupleurum Radix were saikosaponins a， b₁， b₂， b₃， c， d， e， f， and v， and the key targets were fms-related receptor tyrosine kinase 1 （FLT1）， kinase insert domain receptor （KDR）， fibroblast growth factor 2 （FGF2）， vascular endothelial growth factor A （VEGFA）， and signal transducer and activator of transcription 3 （STAT3）. Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks， including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo， providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.