ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

Objective: To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention. Methods: From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated. Results: Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group. Conclusion Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.

ObjectiveTo investigate whether Danggui Shaoyaosan （DSS） inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK）/nuclear factor kappa-B （NF-κB） signaling pathway， thereby delaying the progression of diabetic kidney disease （DKD） and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group， and forty 8-week-old db/db mice were randomly divided into the model group， DSS low-dose group （8.39 g·kg^-1）， DSS medium-dose group （16.77 g·kg^-1）， DSS high-dose group （33.54 g·kg^-1）， and irbesartan group （0.025 g·kg^-1）， with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration， changes in body weight， fasting blood glucose （FBG）， and 24 hour urinary protein （24 h UTP） were observed. After 12 consecutive weeks of administration， hematoxylin-eosin （HE） staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species （ROS） in renal tissue were detected using the dihydroethidium （DHE） method. The expression levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissue were determined. Serum interleukin-1β （IL-1β） and interleukin-6 （IL-6） levels were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of RhoA， ROCK1， and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of fibronectin （FN）， Collagen Ⅳ（Col Ⅳ）， transforming growth factor-β₁ （TGF-β₁）， RhoA， ROCK， and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed significantly increased body weight， FBG， and 24 h UTP levels （P<0.01）， elevated serum IL-1β and IL-6 levels， enlarged glomerular volume， diffuse mesangial expansion， increased mesangial matrix， and marked collagen fiber proliferation in renal tissues. SOD activity was decreased， while MDA， ROS， RhoA， ROCK1， and NF-κB p65 mRNA expression levels were increased （P<0.01）， and the protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 were also elevated （P<0.01）. Compared with the model group， the DSS low-， medium-， and high-dose groups and the irbesartan group showed reductions in body weight， FBG， and 24 h UTP， decreased serum IL-1β and IL-6 levels， varying degrees of improvement in renal histopathology， increased SOD activity， decreased MDA levels， reduced ROS expression， and significantly downregulated RhoA， ROCK1， and NF-κB p65 mRNA expression （P<0.05， P<0.01）， as well as reduced protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 （P<0.05， P<0.01）. ConclusionDSS can alleviate oxidative stress and inflammation， reduce extracellular matrix deposition， and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway， thereby exerting a therapeutic effect on DKD.

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

Extracellular vesicles (EVs) are crucial for facilitating intercellular communication, promoting cell migration, and orchestrating the immune response. Recently, EVs can diagnose and treat tumors. EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy. Furthermore, EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs. Herein, we review the molecular composition, biogenesis, and separation methods of EVs. We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy. Finally, we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective To develop the satisfaction scale on built environment of hygienic city initiative and to evaluate its reliability and validity.Methods By using the qualitative research methods including policy analysis,expert consultation,personal interviews,and quantitative method with statistical analysis,the content of the scale was finally determined.Principal component analysis of exploratory factor analysis was used to construct the dimensions of the scales.The reliability and validity of the scales were evaluated with internal consistency reliability,split-half reliability,content validity,surface validity,and structural validity evaluation methods.Results A satisfaction evaluation scale comprising of 4 dimensions and 20 items was established.The Cronbach's α coefficient of the satisfaction evaluation scale was 0.91,and the Spearman-Brown splitting coefficients of the scale was 0.851.The results of confirmatory factor analysis showed that all test values were in the standard range,which means that content validity of the scale was good.Conclusion The satisfaction scale on the built environment of hygienic city initiative developed in this study has a good reliability and validity.The practical verification of the scale need to be carried out to further explore the applicability of the scale.

Objective To explore the correlation of MPV,NLR,PT,APTT and FIB with early pro-gression of ACI in patients with BAD.Methods A total of 303 ACI patients with BAD admitted in our department of neurology from October 2021 to September 2023 were consecutively recrui-ted,and according to their progression within 7 d of onset,they were divided into progression group(89 cases)and un-progression group(214 cases).The general clinical data,blood routine re-lated indicators(MPV,NLR)and coagulation related indicators(PT,APTT,FIB)were compared between the two groups.Multivariate logistic regression analysis was applied to identify the rela-tionship of above indicators with early progression of ACI in BAD patients.ROC curve was plot-ted to analyze the predictive value of the indictors for disease progression in these patients.Results The progression group had significantly advanced age,larger proportions of diabetes,hyperlipi-demia and stroke history,and increased levels of uric acid,LDL-C,homocysteine,MPV,platelet distribution width,NLR,D-dimer and FIB,and shorter TT,PT and APTT when compared with the un-progressed group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that MPV,NLR,PT,APTT,and FIB were all independent influencing factors for early disease pro-gression of ACI in patients with BAD(P＜0.05,P＜0.01).ROC curve indicated that the AUC value of combined MPV,NLR,PT,APTT and FIB in detecting early disease progression was 0.859(95％CI:0.813-0.905).Conclusion Blood routine(MPV,NLR)and coagulation related indicators(PT,APTT,FIB)are closely associated with the early disease progression of ACI in BAD patients,and these indicators are of high value in predicting the early disease progression.

BACKGROUND:The Yi people have used Sambucus adnata Wall to treat fractures,bruises,arthritis,etc.The author's group found that the active site aqueous extract(SAW-A)and dichloromethane extract(SAW-B)can promote fracture healing by promoting the expression of genes related to osteoblast proliferation,differentiation and maturation,differentiation and maturation.However,the therapeutic effect of methanol extract(SAW-C)at its active site on osteoarthritis is unclear. OBJECTIVE:To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis,and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS:A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days.On the 21st day after modeling,the knee joint of rats was detected by X-ray,the width of the knee joint was measured,oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected,the morphology of the knee joint was observed by hematoxylin-eosin staining,full-thickness cartilage and hyaline cartilage thickness were measured,and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining.The"drug-component-disease-target"network was constructed.Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed,and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION:Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde,while increase the level of superoxide dismutase;relieve joint swelling caused by osteoarthritis;improve the histopathological state of articular cartilage,maintain the thickness of full-thickness articular cartilage,hyaline cartilage and the area of bone trabeculae in subchondral bone;and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect.Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor,AKT1,interleukin-6,MAPK3,and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway.

BACKGROUND:Previous studies showed that extracts of Sambucus adnata Wall.have the ability to promote the proliferation and differentiation of osteoblasts,fracture healing,anti-inflammatory and antioxidant effects,which can effectively alleviate the development of osteoarthritis.Vascular endothelial growth factor,on the other hand,is a biomarker for the evaluation of osteoarthritis severity. OBJECTIVE:To investigate the effect and mechanism of two extracts of Sambucus adnata Wall.(methanol extract SAW-ME and dichloromethane extract SAW-DCE)on angiogenesis in osteoarthritis. METHODS:(1)Rat models of osteoarthritis were established using anterior cruciate ligament transection and given SAW-ME and SAW-DCE.A sham group was set as a control.Immunohistochemistry and immunofluorescence were used to detect the changes of articular vascular endothelial growth factor A in joint tissue and vascular endothelial growth factor and"H"type blood vessels in serum of osteoarthritis rats.(2)Vascular endothelial cells EA.hy926 were used as the research object and intervened with SAW-ME and SAW-DCE.Cell proliferation was then detected by MTT assay.Vascular endothelial growth factor was used to induce EA.hy926 cells,and the model of angiogenesis was replicated.Cell scratch assay and tube formation assay were performed to study the role and mechanism.(3)EA.hy926 cells were used for transcriptome sequencing to analyze the characteristic changes of cell differential genes and related functions after SAW-DCE intervention. RESULTS AND CONCLUSION:(1)SAW-ME and SAW-DCE downregulated the expression of vascular endothelial growth factor A in the rat knee cartilage and reduced the formation of"H"type vessels in osteoarthritis rats.SAW-ME could significantly decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats(P<0.05).SAW-DCE could also decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats,but there was no significant change.(2)Both SAW-ME and SAW-DCE significantly inhibited vascular endothelial cell migration and tube formation,and downregulated the expression of Ang1 and Tie2 proteins.(3)Transcriptome sequencing analysis found that abnormal angiogenesis in osteoarthritis was related to the PI3K/AKT signaling pathway.(4)To conclude,SAW-ME and SAW-DCE can inhibit angiogenesis in the rat model of osteoarthritis,and the mechanism may be related to the Ang1/Tie2 and PI3K/AKT signaling pathways.