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.

ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B₁（AFB₁） in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups： Control （n=6）， AFB₁ （n=7）， and linalool （n=7） groups. Linalool solution （200 mg·kg^-1） was administered preventatively for 14 days， while the control and AFB₁ groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool， AFB₁ solution （1 mg·kg^-1， dissolved in saline） was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin（HE） staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase（ALT）， aspartate transaminase（AST）， γ-glutamyl transferase（GGT）， lactate dehydrogenase（LDH）， alkaline phosphatase（ALP）， total bilirubin（TBil）， direct bilirubin（DBil）， indirect bilirubin（IBil）， malondialdehyde（MDA）， superoxidedismutase（SOD）， catalase（CAT） ， glutathione（GSH）， Fe³⁺， and Fe²⁺ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2（Nrf2） and heme oxygenase-1（HO-1）. Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB₁ group， the liver structure in the linalool group tended to be normal， with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT， AST， GGT， LDH， ALP， TBil， DBil， and IBil （P<0.01）， Fe³⁺ and Fe²⁺ content， and oxidative stress marker MDA （P<0.01）. The levels of antioxidants SOD， CAT， and GSH significantly increased （P<0.01）. Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol^-1（1 cal≈4.186 J）， respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression （P<0.05） and a decrease in HO-1 protein expression （P<0.01） in the linalool group. ConclusionLinalool may protect against AFB₁-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels.

Objective:By analyzing the cost change trend,internal structure change and main influencing factors of diabetes inpatients'hospitalization expenses,it provides empirical basis for promoting the reform of medical service prices,optimizing the internal structure of hospitalization expenses,effectively controlling hospitalization expenses,and reducing the economic burden of diabetes inpatients.Methods:Using the first page data of medical records of 13 426 diabetes inpatients in the target hospital from 2017 to 2021,it analyzes the structural change of diabetes inpatients'hospitalization expenses by using structural change degree and grey correlation degree methods,and analyzes the influencing factors of hospitalization expenses by using linear regression and BP neural network model.Results:Drug expenses and medical technology expenses are the top two in the proportion of total hospitalization expenses of discharged patients with diabetes,and they account for a large proportion in the total hospitalization expenses.The results of structural change and grey correlation show that drug expenses and medical technology expenses are these two factors that cause changes in the total hospitalization cost structure and have a high correlation with the total hospitalization cost,with a cumulative contribution rate of 90.50％.According to the results of linear regression and neural network model,the length of stay is the most important factor affecting the total cost of hospitalization of diabetes patients,followed by the number of operations/procedures and diagnoses.Conclusion:The internal composition of hospitalization expenses for diabetes patients is unreasonable.The proportion of drug expenses and medical technology expenses is too high.The proportion of medical and nursing expenses reflecting the technical labor value of medical personnel is relatively low.The structure of medical income needs to be further optimized.The length of stay is the most critical factor affecting the hospitalization expenses of diabetes patients.Reasonable control of the length of stay can effectively control the unreasonable growth of medical expenses and reduce the economic burden of diabetes patients.

ObjectiveTo explore the effect of Tongluo Jiedu Xiezhuo prescription （TLJDXZ） on alleviating inflammatory response in rats with gouty arthritis （GA） by regulating the formation and release of neutrophil extracellular traps （NETs）. MethodOxonic acid potassium salt solution combined with uric acid sodium solution was used to establish the GA rat model by injection. Seventy-two SD rats were randomly divided into control model， model group， and low-， medium-， and high-dose （1.58， 3.15， and 6.30 g∙kg^-1） TLJDXZ groups， and colchicine group （0.30 mg∙kg^-1）. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to characterize the chemical components of TLJDXZ. HE staining was used to observe the ankle joint tissue structure of rats. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of inflammatory factors interleukin （IL）-1β， IL-6，IL-8， blood uric acid （BUA） tumor necrosis factor （TNF）-α， reactive oxygen species （ROS）， and myeloperoxidase （MPO） in serum and tissue. PicoGreen staining method was used to measure ds-DNA concentration in plasma. Western blot was used to detect the expression of citrullinated histone H3 （Cit-H3） and MPO proteins. Immunofluorescence was used to detect the expression of neutrophil elastase （NE） and MPO. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect peptidylarginine deiminase 4 （PAD4） mRNA expression. ResultCompared with control group， the model group had severe joint swelling， with shed cell debris， synovial and connective tissue proliferation， and inflammatory cell punctate infiltration visible in the joint cavity. Blood circulation， oxidative damage， and inflammation in joint tissues significantly worsened （P<0.05）. The expression of NETs-related proteins Cit-H3， MPO， NE， and PAD4 was significantly upregulated （P<0.05）. Compared with the results in model group， joint damage in the TLJDXZ groups was significantly reduced， and the swelling was alleviated. The inflammatory infiltration in the joint cavity， cartilage and synovial morphology， and joint structure were significantly relieved. TLJDXZ significantly reduced oxidative damage and inflammation in peripheral blood circulation and joint tissues （P<0.05）. The expression of NETs-related proteins Cit-H3， MPO， NE， and PAD4 was significantly downregulated （P<0.05）. ConclusionTLJDXZ can effectively alleviate joint inflammatory response in GA rats， and its mechanism of action may be related to the regulation of the formation and release of NETs.

ObjectiveMetabolomics was utilized to investigate the preventive effect of notoginseng total saponins（NTS） on aspirin（acetyl salicylic acid， ASA）-induced small bowel injury in rats. MethodFifty male SD rats were randomly divided into normal and model groups， NTS high-dose and low-dose groups（62.5， 31.25 mg·kg^-1）， and positive drug group（omeprazole 2.08 mg·kg^-1+rebamipide 31.25 mg·kg^-1）， with 10 rats in each group. Except for the normal group， rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg^-1 daily to establish a small intestine injury model. On this basis， each medication group was gavaged daily with the corresponding dose of drug， and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration， small intestinal tissues of each group were taken for hematoxylin-eosin（HE） staining， scanning electron microscopy to observe the damage， and the apparent damage of small intestine was scored. Serum from rats in the normal group， the model group， and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the data were processed by multivariate statistical analysis， the potential biomarkers were screened by variable importance in the projection（VIP） value≥1.0， fold change（FC）≥1.5 or ≤0.6 and t-test P<0.05， and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database（HMDB） and Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultAfter 14 weeks of administration， the average body mass gain of the model group was lower than that of the normal group， and the NTS high-dose group was close to that of the normal group. Compared with the normal group， the fecal character score of rats in the model group was significantly increased（P<0.05）， and compared with the model group， the scores of the positive drug group and the NTS high-dose group were reduced， but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury， compared with the normal group， the small bowel injury score of the model group was significantly increased（P<0.01）， compared with the model group， the small bowel injury scores of the NTS low and high dose groups were significantly reduced（P<0.05， P<0.01）. Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group， of which 55 were up-regulated and 20 were down-regulated， 76 differential metabolites between the model group and the NTS groups， of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites（salicylic acid， 3-hydroxybenzoic acid and 4-hydroxybenzoic acid）， which were involved in 3 metabolic pathways， namely， the bile secretion， the biosynthesis of folic acid， and the biosynthesis of phenylalanine， tyrosine and tryptophan. ConclusionNTS can prevent ASA-induced small bowel injury， and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats.

Gouty arthritis （GA） is a metabolic disease caused by disorders of purine metabolism and/or abnormal excretion of uric acid in the body. Its pathogenesis is mostly related to dietary structure as well as excessive intake of protein， sugar and fat， and the clinical manifestations are joint redness， swelling， heat and pain， which seriously affect the daily life of patients. Therefore， it is urgent to carry out research on anti-GA drugs. Western drugs for the treatment of GA， such as colchicine， can relieve pain in the short term， but with obvious side effects in long-term treatment. Traditional Chinese medicine has definite efficacy and high safety in the treatment of GA and is more acceptable to patients than western medicine. Modern medical research has concluded that inflammatory factors， oxidative stress， apoptosis and intestinal dysbacteriosis are closely related to the pathogenesis of GA. In-depth research has found that single traditional Chinese medicine and its compounds can regulate Toll-like receptors/myeloid differentiation factor 88 （TLRs/MyD88） signaling pathway， NLR family pyrin domain containing 3 （NLRP3） inflammasome， nuclear transcription factor-κB （NF-κB） and other inflammatory signaling pathways， and further intervene in the downstream cytokines such as interleukin-1β （IL-1β）， interleukin-2 （IL-2）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， peroxisome proliferator-activated receptor γ （PPARγ）， nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-α（IκB-α） and aspartate-specific cysteine protease 1 （Caspase-1） to reduce inflammatory factors and increase anti-inflammatory factors， thereby exerting the anti-GA role. Therefore， this paper summarized and elaborated the experiments of inflammatory response mediated by traditional Chinese medicines and their compounds via regulating inflammatory signaling pathways in recent years， which provides new ideas and theoretical basis for finding more related anti-inflammatory traditional Chinese medicines for the treatment of GA.

Objective: To apply and evaluate the effect of empowerment educational program on AIDS prevention and treatment among freshmen in one university. Methods: The method of two stage stratified sampling was used to select the experimental and control group. The traditional health education was implemented among the control group, and the empowerment education was implemented for the experimental group. The effect of the two groups was compared before and after intervention. Results: For experimental group, the awareness rate of AIDS(65.02%) ( χ 2=61.02， P <0.01) and the overall score of attitude and behavior(16.71± 2.53 )( t =-2.66， P <0.05) were significantly improved after intervention(82.96%，18.58±1.95). For the control group, there was significant difference in awareness rate of AIDS after intervention(67.70% vs 96.02%， χ 2=18.64, P <0.05), while there was no statistical difference in overall score of attitude and behavior after intervention(16.52±1.50 vs 17.16±1.57， t =-1.51, P =0.14). There was no significant difference in awareness rate between the two groups before intervention ( χ 2=0.36, P =0.55), but there was a statistical difference after intervention ( χ 2=20.42, P <0.01). There was statistical difference in attitude and behavior scores between the two groups after intervention ( P <0.05). Conclusion Empowerment educational program can improve the awareness rate of AIDS among college students, help to establish an objective attitude towards AIDS and infected patients, and to reduce high risk sexual behavior, also it is more effective compared to traditional education method.

Objective:To investigate the relationship between single nucleotide polymorphism (SNPs) of Zeste homolog enhancer 2 (EZH2) gene and the risk of breast cancer.Methods:Recruiting 1 039 breast cancer patients and 1 040 controls at 22 referral hospitals nationwide in China, the genotype distribution of 3 SNPs loci of EZH2 genes was observed to detect the correlation between different genotypes and the risk of breast cancer genotypes EZH2 expression in breast cancer tissues and its correlation with patient prognosis were analyzed using breast cancer data from the database.Results:EZH2 rs6464926 CC genotype was compared with TT genotype (TT vs. CC: OR=1.362, 95% CI: 1.063-1.746, P=0.015) and dominant model (TC+TT vs .CC: OR=1.22, 95% CI: 1.004-1.483, P=0.045) .In women with BMI ≥24 kg/m 2, the TC genotype ( P=0.050), TT genotype ( P=0.025) and dominant model (TC+TT, P=0.021) of rs6464926 locus were significantly different from CC genotype in cancer risk. rs6464926 was correlated with EZH2 gene expression ( P=6.89E-47). EZH2 gene is highly expressed in breast cancer tissues, and patients with high expression were associated with shorter OS ( HR=1.27, P=0.013), DMFS ( HR=1.37, P<0.01), and RFS ( HR=1.44, P<0.01). Conclusions:The polymorphism rs6464926 of EZH2 gene is associated with breast cancer susceptibility in Chinese women. rs6464926 might regulate breast cancer risk and prognosis by changing EZH2 expression.

Objective:Rapid assessment of the outcome after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is an important clinical issue. In this study, an electrocardiogram (ECG) analysis method based on dynamic learning was proposed.Methods:A total of 203 patients with ACS after successful PCI were enrolled for prospective analysis at the Emergency Department of Qilu Hospital of Shandong University from April 2019 to December 2020. All patients were divided into group without ≥70% postoperative stenosis ( n=72) and group with ≥ 70% postoperative stenosis ( n=131) according to the presence of 70% or more stenosis after PCI. The clinical data of ACS patients were collected and analyzed by χ2 test, t-test, or Mann-Whitney test. ECGs were recorded before and 2 h after PCI, and were dynamically analyzed to generate cardiodynamicsgram (CDG) using dynamic learning. In the group without ≥ 70% postoperative stenosis, the model and CDG index for evaluating myocardial ischemia were obtained by training support vector machine (SVM) using 10 times 10-fold cross-validation. Results:There was no significant difference in clinical data between the two groups. The prediction accuracy and sensitivity of the support vector machine model for myocardial ischemia in group without≥70% postoperative stenosis were 73.61%, and 84.72% respectively. CDG transformed from disorderly to regular after PCI, and CDG index decreased significantly ( P<0.001): 90.28% (65) patients in group without≥70% postoperative stenosis, and 79.39% (104) patients in group with≥70% postoperative stenosis had lower CDG indexes than before PCI. Conclusions:In this study, CDG obtained by dynamic learning can intuitively and effectively evaluate the changes of myocardial ischemia before and after PCI, which is helpful to assist clinicians to formulate the next treatment plan.