ObjectiveThis paper aims to observe the role of Danlou tablet in treating coronary heart disease （CHD） with phlegm-stasis intermingling syndrome in minipigs by improving platelet function and explore the potential pharmacological mechanism of Danlou tablet in regulating platelet function by using proteomics technology. MethodsThirty Bama minipigs were randomly divided into a normal control group （6 pigs） and a high-fat diet group （24 pigs）. After 2 weeks of high-fat diet feeding， the high-fat diet group was randomly subdivided into a model group， an atorvastatin group （1 mg·kg^-1）， and Danlou tablet groups （0.6 g·kg^-1 and 0.3 g·kg^-1）. All groups continued to receive a high-fat diet for 8 weeks after the procedure. The normal control group was given a regular diet， underwent only coronary angiography， and did not receive an interventional injury procedure. The model group and each administration group were fed a high-fat diet. Two weeks later， they underwent a coronary angiography injury procedure. After the procedure， drugs were mixed into the feed every morning for 8 consecutive weeks， with the minipigs maintained on a continuous high-fat diet during this period. Quantitative proteomics technology was further used to study platelet proteins， and differential proteins were obtained by screening. Bioinformatics analysis was performed to analyze key regulatory proteins and biological pathways involved in the therapeutic effect of Danlou tablet on CHD with phlegm-stasis intermingling syndrome. ResultsCompared with the normal control group， the model group showed a significant increase in total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） of minipigs' serum （P<0.01）， a significant shortening in prothrombin time of （PT） （P<0.01）， a coagulation function index， and an increase in whole blood viscosity （P<0.01） and platelet aggregation rate （P<0.01）. Moreover， the platelet morphology was altered， and the contents of endothelin-1 （ET-1） and nitric oxide （NO） were significantly increased （P<0.01）. Hemodynamic parameters were obviously abnormal， including significantly decreased systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， and left ventricular maximal positive dp/dt （LV+dp/dt_max） （P<0.01）. Left ventricular maximal negative dp/dt （LV-dp/dt_max） was significantly increased （P<0.01）. Besides， there were myocardial cell hypertrophy， obvious edematous degeneration， massive interstitial inflammatory cell infiltration， high degree of fibrosis， and coronary endothelial atherosclerosis. TC and TG levels in minipigs' serum were significantly reduced in Danlou tablet groups with 0.6 g·kg^-1 and 0.3 g·kg^-1 （P<0.05， P<0.01）， compared with those in the model group. LDL-C was decreased in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. The whole blood viscosity under low and high shear conditions was significantly reduced in the Danlou tablet group with 0.6 g·kg^-1 （P<0.05）. In groups with all doses of Danlou tablet， maximum aggregation rate （MAR） and average aggregation rate （AAR） were significantly decreased （P<0.05， P<0.01）， and platelets' morphological changes such as pseudopodia extension were reduced. ET-1 levels in the serum were significantly reduced. In the Danlou tablet group with 0.6 g·kg^-1， NO level in the serum was reduced （P<0.05）. In groups with all doses of Danlou tablet， DBP and MAP were significantly increased （P<0.05）. In the Danlou tablet group with 0.6 g·kg^-1， LVSP and LV+dp/dt_max were significantly increased （P<0.05， P<0.01）， and LV-dp/dt_max was significantly decreased （P<0.05）. In groups with all doses of Danlou tablet， edematous degeneration in myocardial tissue was milder， and coronary artery lesion degree was significantly alleviated. Compared with the normal control group， there were 94 differentially expressed proteins in the model group， including 81 up-regulated and 13 down-regulated proteins. Compared with the model group， the Danlou tablet group with 0.6 g·kg^-1 showed 174 differentially expressed proteins， including 100 up-regulated and 74 down-regulated proteins. A total of 30 proteins were reversed after Danlou tablet intervention. Bioinformatics analysis revealed that its pharmacological mechanism may exert anti-platelet activation， aggregation， and adhesion effects through biological pathways such as regulation of actin cytoskeleton， platelet activation pathway， Fcγ receptor-mediated phagocytosis， as well as proteins such as growth factor receptor-bound protein 2 （GRB2）， Ras-related C3 botulinum toxin substrate 2 （RAC2）， RAC1， and heat shock protein 90 alpha family class A member 1 （HSP90AA1）. ConclusionDanlou tablet can effectively reduce platelet activation and aggregation， exerting a good therapeutic effect on CHD with phlegm-stasis intermingling syndrome in minipigs. Its pharmacological mechanism may involve regulating biological pathways such as actin cytoskeleton and platelet activation pathway， as well as proteins like GRB2， RAC2， RAC1， and HSP90AA1， thereby exerting a pharmacological effect in anti-platelet activation， aggregation， and adhesion.

ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

OBJECTIVE To explore the mechanism of Shenqi guben formula （SQGB） in improving cancer-related fatigue （CRF） based on network pharmacology and cellular experiments. METHODS Active components of SQGB and CRF-related targets were identified on the basis of databases such as the Traditional Chinese Medicine Systems Pharmacology platform. An in vitro CRF cell model was established by inducing A549 cells with interleukin-17 （IL-17）. Cells were treated with low （1.0 mg/mL） or high （1.5 mg/mL） concentrations of SQGB. The effects on cell viability， migration， apoptosis， inflammatory factors， mRNA expression， apoptosis-related proteins and key proteins 011） of IL-17 signaling pathway were evaluated using scratch assay， flow cytometry， ELISA， real-time fluorescent quantitative PCR and Western blot analysis. RESULTS SQGB contained 84 active components acting on 209 potential CRF targets. Among E-these， quercetin， kaempferol， and luteolin were identified as the core components of the compound. Core targets included tumor protein p53， AKT serine/threonine kinase 1， IL-6， and tumor necrosis factor （TNF）. IL-17， TNF and phosphatidylinositol-3- kinase-serine/threonine protein kinase （PI3K/Akt） signaling pathways were identified as crucial pathways. Compared with IL-17 intervention group， the cell migration rate， B-cell lymphoma 2 （Bcl-2） protein expression， the levels of IL-6 and TNF-α in the supernatant， mRNA expression of IL-17 receptor A （IL-17RA）， TNF-α， and IL-6， as well as the protein expression of IL-17RA and nuclear factor kappa-B p65 subunit （p65）， and phosphorylated （p）-p65/p65 ratio in IL-17+SQGB low- and high- quality concentration groups were all significantly decreased or down-regulation （P＜0.05）； the apoptosis rate， expression levels of Bcl-2 associated X protein （Bax） and cleaved caspase-3 protein， the ratio of Bax/Bcl-2， the expression level of p-p38 protein， and the p- p38/p38 ratio were all significantly increased or up-regulated （P＜0.05）. Moreover， the improvement effects of these indicators were mostly better in the high-quality concentration groups compared to the low-quality concentration groups （P＜0.05）. CONCLUSIONS SQGB ameliorates CRF by regulating the IL-17 signaling pathway， inhibiting the expression of inflammatory factors， and activating p38 MAPK-dependent apoptosis pathway.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

The seed kernel of Momordica cochinchinensis, i.e., Momordicae Semen, is used for medicinal purposes, but to date, no research has been reported on its chemical constituents. In this study, the chemical constituents of Momordicae Semen were investigated for the first time using silica gel column chromatography, semi-preparative HPLC, HR-MS, and NMR. As a result, eight compounds were isolated and identified as: p-hydroxybenzoic acid-7-O-trehaloside(mubeside A, 1), 2,6-dimethoxyphenol-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside B, 2), 1-O-p-methoxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside C, 3), 1-O-p-hydroxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside D, 4), gypsogenin-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(5), quillaic acid-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(6), violanthin(7), and kaempferitrin(8). Compounds 1-4 are new compounds, while compounds 5-8 were isolated from Momordicae Semen for the first time.
Glycosides/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid

To investigate the mechanism of Jianpi Qutan Formula in regulating the balance between classically activated macrophages(M1) and alternatively activated macrophages(M2) in atherosclerotic plaques through phosphorylation and activation of the signal transducer and activator of transcription 6(STAT6), thereby reducing inflammation, increasing plaque stability, and exerting anti-atherosclerosis(AS) effects. An AS model was established by feeding apolipoprotein E(ApoE)~(-/-) mice with atherosclerotic chow for 8 weeks. The ApoE~(-/-) mice were randomly divided into a model group(Mod group), a Jianpi Qutan Formula group(JPQT group, 8.97 g·kg~(-1)), and a Atorvastatin Calcium Tablets group(ATO group, 1.3 mg·kg~(-1)) according to a random table method, with 10 mice in each group. Additionally, 10 male C57BL/6J mice of the same age, fed with a normal diet, were set as the control group(Con group). The JPQT and ATO groups received their respective treatments via oral gavage for 8 consecutive weeks, while the Con and Mod groups were administered an equivalent volume of saline. Body weight was continuously monitored, and after blood collection, total cholesterol(TC) and triglyceride(TG) levels in the serum of each group were compared. Hematoxylin-eosin(HE) staining and oil red O staining were used to observe plaque formation in aortic tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression levels of pro-inflammatory cytokines interleukin(IL)-6 and IL-12, as well as the anti-inflammatory cytokine IL-10. Immunofluorescence was used to detect the positive expression of aortic cluster of differentiation(CD)86 and CD206. Western blot analysis was conducted to detect the protein expression levels of aortic inducible nitric oxide synthase(iNOS), arginase 1(Arg1), STAT6, and p-STAT6. Compared to the Con group, the Mod group exhibited increased body weight and blood lipid levels, disordered aortic structure, significant AS plaque formation accompanied by extensive lipid deposition, and elevated serum levels of pro-inflammatory cytokines IL-6 and IL-12, as well as elevated CD86 and iNOS protein levels. In contrast, the serum levels of the anti-inflammatory cytokine IL-10, along with the protein expression levels of CD206, Arg1, and p-STAT6/STAT6, were reduced. Compared to the Mod group, the drug intervention groups showed improvements in body weight and lipid metabolism, with a more significant improvement in aortic structure, reduced lipid accumulation, decreased serum levels of IL-6 and IL-12, and lower CD86 and iNOS protein levels. Meanwhile, levels of IL-10, CD206, Arg1, and p-STAT6/STAT6 increased. Jianpi Qutan Formula improves AS by regulating the imbalance in M1/M2 macrophage polarization, and its mechanism is likely closely related to the activation of the STAT6 signaling pathway.
Animals ; Atherosclerosis/metabolism* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Macrophages/cytology* ; Mice, Inbred C57BL ; STAT6 Transcription Factor/immunology* ; Humans ; Apolipoproteins E/genetics* ; Interleukin-6/immunology*

To study the therapeutic effect and mechanisms of ethyl syringate(MD) on ulcerative colitis(UC), the MTT assay was used to detect the proliferation inhibition of RAW264.7 cells and HT-29 cells by different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)). UC cell models were constructed by inducing RAW264.7 cells and HT-29 cells with lipopolysaccharide(LPS) and tumor necrosis factor-α(TNF-α). An animal model was established by inducing mice with 2.5% dextran sulfate sodium(DSS) to verify the therapeutic effect of MD on UC. A control group, a model group(LPS or TNF-α), and groups treated with different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)) were set up in this study. Nitric oxide(NO) levels were measured using a NO detection kit. Intracellular reactive oxygen species(ROS) levels were assessed using a laser confocal microscope and ROS kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect changes in the levels of interleukin-6(IL-6), TNF-α, interferon-γ(INF-γ), interleukin-10(IL-10), and myeloperoxidase(MPO) in cells and animal tissues. Western blot was used to detect the expression levels of phosphorylated Janus kinase 2(p-JAK2), Janus kinase 2(JAK2), phosphorylated signal transducer and activator of transcription 3(p-STAT3), signal transducer and activator of transcription 3(STAT3), zonula occludens-1(ZO-1), occludin, and claudin-1 in cells and animal tissues. The results showed that MD can improve the inflammatory response by inhibiting the production of NO and ROS and regulating the expression of inflammatory factors. It significantly reduced the disease activity index(DAI) in mice, improved the shortening of the colon, and repaired intestinal epithelial damage by inhibiting the activation of the JAK2/STAT3 pathway, thereby exerting anti-UC activity.
Animals ; Colitis, Ulcerative/chemically induced* ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Mice ; Humans ; Signal Transduction/drug effects* ; Male ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism* ; Nitric Oxide/metabolism* ; HT29 Cells ; Salicylates/administration & dosage* ; Protective Agents/administration & dosage*