OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules， and determine the contents of 12 chemical components. METHODS Identification and content determination were performed by using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1% formic acid solution （gradient elution）； the electrospray ion source was used to scan in the positive ion multi-reaction detection mode. The mass charge ratio （m/z） 631.3→546.4， 631.3→921.4 was the detection ion pair for tortoiseshell glue， and the m/z 765.4→554.0， 765.4→733.0 was the detection ion pair for antler glue. The determination method for 12 chemical components was as follows： Accucore C18 column， methanol-0.1% formic acid as mobile phase （gradient elution）； scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode. RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min， respectively； the linear relationship of 12 chemical components was good within their respective concentration ranges， such as astragaloside Ⅳ， calycosin-7-O-β-D-glucoside， calycosin， chlorogenic acid， ferulic acid， betaine， amygdalin， rutin， hydroxysafflor yellow A， hyperoside， loganin， cyasterone （r＞0.999）； RSDs for precision， stability （24 h） and reproducibility tests were all less than 5%. The average sample recovery rates ranged from 98.04% to 101.08%. The average contents of 12 components were 1.83， 25.73， 13.76，56.71， 23.80， 49.82， 807.49， 15.01， 317.02， 60.21， 202.71 and 17.70 μg/g， respectively. CONCLUSIONS In this study， tortoiseshell glue and antler glue in Qixiong zuogui granules are identified， and the contents of 12 chemical components therein are determined. This provides a reference for the quality control of this granule.

Sophora Flavescens is the dried root of the leguminous plant Sophora Flavescens Ait. It was first published in Shen Nong's Herbal Classic. Sophora Flavescens contains a variety of active ingredients, mainly including matrine and oxymatrine, with anti-inflammatory, anti-tumor, anti-arrhythmia, disease-resistant pathogenic microorganisms and other pharmacological effects. Clinically, the compound preparations of Sophora Flavescens include Compound KuShen injection and KuShen gel and so on, which can be used to treat many types of cancers and improve skin, mucous pruritus, pain and other symptoms. Due to the poor bioavailability, the structure of matrine needs to be reformed. MASM, matrine derivative, only needs a low concentration to have a good therapeutic effect on sepsis and liver fibrosis. In this article, the chemical composition, pharmacological effects, compound preparations and structural modification of matrine were mainly discussed, aiming to provide a theoretical basis for the clinical application of Sophora Flavescens and the development of new drugs.

Matrine is an alkaloid compound isolated and extracted from the traditional Chinese medicinal plant Sophora flavescens, which has anti-tumor, anti-inflammatory, and anti-viral effects. However, its clinical application has been limited due to its low in vivo activity, short duration of efficacy, and significant toxic side effects. In response to this challenge，pharmaceutical experts modified the structure of Matrine to obtain derivatives that addressed its limitations. Currently, research on the anti-tumor effects of Matrine and its derivatives is more prevalent, while research in inflammatory-related diseases still needs further strengthening.The progress on the role and mechanism of Matrine and its derivatives in inflammatory diseases were summarized in this paper, which offered valuable insights for the development of therapeutic agents based on Matrine.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Objective:To investigate the effect of decarbromodiphenyl ether(BDE-209)exposure on the migration ability of triple-negative breast cancer(TNBC)cells and to explore the underlying mechanism.Methods:Human TNBC MDA-MB-231 cells were divided into blank control group and BDE-209 exposure groups(treated with 0.02,0.20,2.00,20.00 and 200.00 ng/mL BDE-209 in high glucose DMEM).Extracellular vehicles(EVs)secreted by MDA-MB-231 cells were isolated by differential ultracentrifugation.Transmission electron microscopy(SEM),nanoparticle tracking analysis(NTA)and Western blotting were performed to characterize the EVs.The effect of the EVs induced by BDE-209 exposure(EVs-BDE-209)on the migration and invasion of MDA-MB-231 cells was detected by wound-healing assay and Transwell test.qRT-PCR was used to measure the miR-221 level in EVs-BDE-209.The expression of MMP9 in MDA-MB-231 cells was determined by Western blotting.Results:Compared with the blank control,BDE-209 exposure increased the tumor cell-derived EVs in dose-dependent manner.The MDA-MB-231 cells co-cultured with EVs released by 200.00 ng/mL BDE-209 exposure showed an 86%increase in cell migration rate,a 1.32-fold higher number of membrane-penetrating cells,a 2.71-fold higher expression level of miR-221,and a 1.62-fold higher expression level of MMP9 compared with the blank control group(all P<0.05).While transfection with anti-miR-221 antibody to decrease miR-221 level in EVs significantly reversed the increased invasion ability of the MDA-MB-231 cells treated with EVs-BDE-209.Conclusion:BDE-209 exposure may promote metastasis potential of MDA-MB-231 cells via EVs-BDE-209 transmitted miR-221.

Objective To analyze the changes in left ventricular deformation function in patients with diffuse large B-cell lymphoma(DLBCL)treated with different doses of anthracycline chemotherapy using 3D speckle-tracking imaging(3D-STI).Methods 66 DLBCL patients receiving anthracycline chemotherapy were enrolled.Based on the cumulative dose of anthracycline received,the patients were divided into a high-dose group(＞360 mg/m2,n=39)and a low-dose group(≤360 mg/m2,n=27).Patients underwent transthoracic echocardiography before chemotherapy and within one week after completion of the entire chemotherapy cycle.Left ventricular global longitudinal strain(LVGLS),left ventricular global circumferential strain(LVGCS),and other indices were analyzed using 3D-STI to assess changes in left ventricular deformation indices after chemotherapy and between two groups.Results Compared to baseline,DLBCL patients showed significant reductions in LVGLS,LVGCS and left atrial global longitudinal strain(LAGLS)after treatment completion(P＜0.001).When comparing the high-dose group with the low-dose group,there was a significant increase in relative LVGCS change rate at the end of chemotherapy(21.12[6.52,35.37]vs 5.49[-14.73,27.01];P=0.03).However,there were no statistically significant differences in relative left ventricular ejection fraction(LVEF),LVGLS,LVGCS,LVEF change rate,or LVGLS change rate between the two groups.Conclusions 3D-STI can be a potential method to identify the sub-clinical deterioration of left ventricular systolic function in patients received anthracycline chemotherapy,the difference of change rate of LVGCS may predict the variation of sub-clinical deterioration of left ventricular function between patients received high and low doses of anthracycline chemotherapy.

Sepsis is a severe and life-threatening symptom that poses a significant risk to human health.Treatment mainly involves supportive care,but research on new drugs is ongoing.Advancements have been achieved in the management of immune function,inflammatory pathway,blood coagulation,and vascular endothelial homeostasis in sepsis.The advances in the treatment of sepsis in recent years were these reviewed in this article.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

AIM:To investigate the impact of platycodin D(PD)on the viability,migration,invasion,apop-tosis and cell cycle of osteosarcoma cells in vitro,along with its underlying mechanisms.METHODS:Human osteosarco-ma cells MG63 and U2OS were divided into control group(0 μmol/L)and PD treatment group(6.25,12.5,25,50 and 100 μmol/L,respectively).Human osteosarcoma cells MG63 and U2OS were categorized into control groups(0 μmol/L PD)and PD treatment groups(6.25,12.5,25,50 and 100 μmol/L).The CCK-8 assay determined cell viability and identified effective treatment concentrations.MG63(15 μmol/L PD)and U2OS(25 μmol/L PD)were specifically ana-lyzed.Cell scratch and Transwell assays assessed migration and invasion.Hoechst 33342 staining examined nuclear mor-phological changes.Flow cytometry analyzed cell cycle distribution and apoptosis rate.Western blot measured protein ex-pression levels:cleaved caspase-3,cleaved PARP,c-Jun N-terminal kinase(JNK),p-JNK,B-cell lymphoma-2(Bcl-2),Bcl-2-ssociated X protein(BAX),matrix metalloproteinase 2(MMP-2),MMP-9,cyclin-dependent kinase 4(CDK4),cyclin D1,CDK1,cyclin B1,extracellular signal-regulated kinase(ERK)and p-ERK.Proteome sequencing of MG63 cells was performed.RESULTS:PD treatment significantly decreased cell survival,scratch healing rate,and invasive cell numbers,while increasing apoptosis rates(P<0.05).Morphological changes such as nuclear hyperchroma-tism and fragmentation were observed in PD-treated cells.PD induced G2/M phase arrest in MG63 and G0/G1 phase arrest in U2OS cells.PD treatment upregulated BAX,cleaved caspase-3,cleaved PARP,and p-JNK/JNK,while downregulat-ing Bcl-2,MMP-2,MMP-9,CDK4,cyclin D1,CDK1,cyclin B1,and p-ERK/ERK(P<0.05).Proteome sequencing re-vealed PD's involvement in cell division,cell cycle regulation,focal adhesion,apoptosis,and the MAPK signaling path-way.CONCLUSION:PD inhibits cell viability,migration,and invasion of osteosarcoma cells in vitro,while promoting apoptosis and inducing cell cycle arrest.These effects are likely mediated through modulation of the MAPK signaling path-way.