OBJECTIVE To investigate the effects of ertugliflozin on pharmacokinetic of sorafenib and donafenib in rats and explore the mechanism. METHODS Twenty-four male SD rats were randomly divided into four groups， with 6 rats in each group. Groups A and B were respectively gavaged with 0.5% sodium carboxymethyl cellulose solution and ertugliflozin （1.5 mg/kg） for 7 consecutive days， and both were given sorafenib （100 mg/kg） on the 7th day. Groups C and D were administered intragastrically in the same way as those in Groups A and B， respectively， for the first 7 days； after the drug administration on the 7th day， all rats in Groups C and D were further gavaged with donafenib （40 mg/kg）. Blood samples were collected at different time points before and after administration of sorafenib or donafenib， the concentrations of sorafenib in plasma of rats in groups A and B and donafenib in groups C and D were determined by UPLC-MS/MS method. The pharmacokinetic parameters were calculated by DAS 2.1.1 software. Six additional rats were randomly divided into blank control group and ertugliflozin group， with three rats in each group. Blank control group was given 0.5% sodium carboxymethyl cellulose intragastrically， while rats in ertugliflozin group were given ertugliflozin （1.5 mg/kg） once a day for 7 consecutive days. After the last administration， the mRNA expression levels of uridine diphosphate glucuronosyl transferase 1A7 （UGT1A7）， breast cancer resistance protein （BCRP）， and P-glycoprotein （P-gp） in the liver and small intestine tissues of the rats were detected. RESULTS Compared with group A， the AUC0-t， AUC0-∞， cmax， tmax， MRT0-t and MRT0-∞ of sorafenib in group B were decreased significantly， while CL and V were increased significantly. Compared with group C， the AUC0-t， AUC0-∞ ， tmax， cmax and MRT0-t of Δ donafenib in group D were decreased significantly， while V and CL were increased significantly （P＜0.05）. mRNA expression of UGT1A7， P-gp and BCRP in the liver tissue and small intestine of rats were not significantly affected after intragastric administration of ertugliflozin for 7 consecutive days. CONCLUSIONS Ertugliflozin can affect the pharmacokinetics of sorafenib and donafenib in rats and decrease the plasma exposure of them significantly. However， its mechanism of action may not be through the regulation of related metabolic enzymes and transporters. When using drugs in combination clinically， one should be vigilant about the potential for disease progression due to poor therapeutic effects.

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.

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry* ; Starch/chemistry* ; Multivariate Analysis ; Water/chemistry* ; Terpenes/analysis* ; Plant Roots/chemistry* ; Plant Tubers/chemistry* ; Drugs, Chinese Herbal/chemistry*

This study systematically analyzed the global research landscape, technological composition, and core patents in the field of networks target and network pharmacology, and proposes further suggestions based on the IncoPat patent citation database and VOSviewer bibliometric network visualization tool. Using patent literature metrics and scientific knowledge mapping method, technological innovation pathways, research hotspots, and future directions in this field were further revealed. In particular, this field is moving towards data-driven, intelligent, and systematic approaches. Patent analysis indicated that most patent applications in this domain focused on traditional Chinese medicine(TCM), which have provided key engineering technical approaches to explore and solve complex problems of TCM. By integrating big data and artificial intelligence technologies, network targets and network pharmacology have conferred high-precision screening and quality control of key components and targets in herbal formulations and prescriptions, accelerating the clinical translation and industrialization of TCM-based new drugs and health products with medicine-food homology. Therefore, it is essential to optimize the patent protection system and establish integrated technology platforms in this field for ensuring the competitiveness of technological achievements in research and clinical application. These efforts will advance the widespread application and high-quality development of TCM modernization, precision medicine, and innovative drug discovery.
Bibliometrics ; Patents as Topic ; Humans ; Medicine, Chinese Traditional ; Network Pharmacology/trends* ; Drugs, Chinese Herbal/pharmacology*

BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans ; Glioma/psychology* ; Palliative Care/methods* ; Quality of Life ; Psychometrics ; Brain Neoplasms/psychology*

OBJECTIVE: To compare the effects of different concentrations of ropivacaine femoral nerve block on postoperative pain and early exercise fllowing total knee arthroplasty(TKA). METHODS: A total of 90 patients who underwent primary TKA between September 2022 and February 2023 were consecutively enrolled in this study. The cohort consisted of 34 males and 56 females, with a mean age of (66.66±7.03) years old. According to different concentrations of ropivacaine, patients were divided into 0.1% group, 0.2% group and 0.4% group, with 30 patients in each group. The age, gender, body mass index(BMI), American Society of Aneshesiologists(ASA) grade, operation time, anesthesia time, tourniquet using time, Post Anesthesia care unit(PACU) stay duration, ambulation time, first reaching to Bromage 0 grade time, visual analogue scale(VAS), hospitalization period and postoperative adverse reactions were compared among the three groups. RESULTS: All 90 patients were followed up for an average of (31.56±5.62) days, and no postoperative adverse reactions occurred. There were no significant differences among the three groups in terms of age, gender, BMI, ASA classification, operation time, anesthesia time, tourniquet application time, PACU stay duration, and hospitalization period (P>0.05). Significant differences were observed in VAS scores at 1, 2, 4, 6, and 12 hours post-operation among the three groups (P<0.05). Additionally, significant variations were noted in ambulation time and the first reaching to Bromage level 0 time among the three groups (P<0.05). In terms of postoperative pain, the VAS of the 0.1% group at 1, 2, 4, 6, and 12 hours after surgery(1.93±0.52), (2.57±0.77), (3.10±0.71), (3.10±0.71), (3.07±0.45) points were higher than those of the 0.4% group (1.57±0.50), (2.10±0.55), (2.23±0.57), (2.47±0.73), (2.50±0.57) points, and the differences were statistically significant (P<0.05);the VAS of the 0.1% group at 4, 6, and 12 hours after surgery were higher than those of the 0.2% group (2.43±0.57), (2.53±0.57), (2.63±0.56) points, and the differences were statistically significant (P<0.05);there was no statistically significant difference in VAS between the 0.2% group and the 0.4% group (P>0.05). In terms of early postoperative mobility, the time to ambulation time (8.30±2.76) h and the time to achieve the first Bromage grade 0 (6.13±2.18) h were significantly prolonged in the 0.4% group compared to both the 0.1% group (6.93±1.76) h, (4.17±1.18) h and the 0.2% group (6.53±1.59) h, (4.87±1.53) h. No statistically significant differences were observed between the 0.1% and 0.2% groups (P>0.05). CONCLUSION 0.2% ropivacaine femoral nerve block can effectively reduce postoperative pain after TKA and can perform early exercise earlier.
Humans ; Male ; Female ; Ropivacaine/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged ; Nerve Block/methods* ; Femoral Nerve/drug effects* ; Middle Aged ; Pain, Postoperative/drug therapy* ; Anesthetics, Local/administration & dosage* ; Amides

OBJECTIVE: To investigate the pharmacological mechanism of Compound Xuanju Capsule in the treatment of erectile dysfunction (ED) by using network pharmacology and molecular docking technology. METHODS: The active ingredients and targets of Compound Xuanju Capsule were screened using Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP). TTD, OMIM, DrugBank and GeneCards databases were used to obtain genes related to ED, and the union of the results was taken as the disease genes of ED. The common target of drug and disease was taken as the potential target of Compound Xuanju Capsule in ED, and the drug-disease interaction network was constructed by using Cytoscape software. The protein-protein interaction (PPI) network was constructed by using String database, which was then imported into Cytoscape to identify the key target. Based on the drug-disease intersection genes, GO and KEGG enrichment analyses were performed to predict the relevant signaling pathways and molecular mechanisms of Compound Xuanju Capsule for the treatment of ED. Autodock software was used to perform molecular docking between the active ingredients and the core targets. RESULTS: Forty chemical components of Compound Xuanju Capsule were screened, and 239 predicted targets were obtained. A total of 1 907 ED-related genes were screened, and 97 common targets were identified between Compound Xuanju Capsule and ED, among which the core targets included EGFR, ESR1, HIF1A, PTGS2, and STAT3. The signaling pathways obtained by KEGG enrichment analysis included calcium signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, relaxin signaling pathway, Serotonergic synapse signaling pathway. The molecular docking results showed that there were molecular binding sites between the key active ingredients and the core targets with strong binding activity. CONCLUSION Compound Xuanju Capsule may treat ED through multi-target pathways such as anti-inflammatory and improving cellular oxidative stress.
Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/drug therapy* ; Molecular Docking Simulation ; Male ; Humans ; Signal Transduction ; Protein Interaction Maps ; Network Pharmacology ; Capsules ; Medicine, Chinese Traditional

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice