The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).

The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

The hippocampus, a major component of the limbic system, is the most important region related to emotion regulation and memory processing. Cognitive impairment and depressive symptoms observed in Alzheimer's disease (AD) patients may be attributed to hippocampal damage caused by amyloid β-protein (Aβ). Our previous studies have demonstrated that a steroid sulfatase inhibitor DU-14 can enhance hippocampal synaptic plasticity and spatial memory abilities in a chronic AD murine model by counteracting the toxic effects of Aβ. However, limited experimental evidence exists regarding the efficacy of steroid sulfatase inhibitor on depressive symptoms in AD animal models. In this study, we investigated the effects of DU-14 on depressive symptoms and theta-band neuronal oscillations in rats with intrahippocampal injection of Aβ_1-42 using various behavioral tests such as sucrose preference test, tail suspension test, forced swimming test, and in vivo hippocampal local field potential (LFP) recording. The results demonstrated that, in comparison to the control group: (1) rats in the Aβ group exhibited a decrease in sucrose preference, indicating a loss of interest in pleasurable activities; (2) rats in the Aβ group displayed aggravated depressive-like behavior characterized by prolonged immobility time during tail suspension and forced swimming tests; (3) Aβ disrupted the induction of theta rhythm via tail pinch stimulation, and resulted in a significant reduction in peak power of theta rhythm. In contrast to the Aβ group, pretreatment with DU-14 resulted in: (1) a significant improvement in Aβ-induced anhedonia, as evidenced by increased sucrose preference; (2) significant alleviation of Aβ-induced despair and depressive-like behaviors, reflected by reduced immobility time during tail suspension and forced swimming tests; (3) successful mitigation of Aβ-mediated inhibition on bilateral hippocampal theta rhythm. These findings indicate that steroid sulfatase inhibitor DU-14 can counteract neurotoxicity induced by Aβ, and prevent Aβ-induced depressive-like behavior and suppression of theta rhythm.
Animals ; Amyloid beta-Peptides/toxicity* ; Rats ; Depression/physiopathology* ; Theta Rhythm/drug effects* ; Hippocampus/physiopathology* ; Male ; Rats, Sprague-Dawley ; Alzheimer Disease/physiopathology* ; Steryl-Sulfatase/antagonists & inhibitors* ; Peptide Fragments ; Behavior, Animal/drug effects*

This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies