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).

Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals ; Mice ; Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Light ; Cytokines/genetics* ; Humans

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Objective:To investigate the mechanism of Yunshi Ganmao Heji against respiratory syncytial virus (RSV) infection based on network pharmacology and in vivo experiments. Methods:Network pharmacological prediction: Several databases including TCMSP and GeneCards were used to predict the active ingredients and targets of Yunshi Ganmao Heji in the intervention of RSV infection. Cytoscape 3.2.1 software was used to construct the traditional Chinese medicine component-disease target network diagram. The interactions between proteins were analyzed by STRING database. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using Metascape database. Molecular docking technology was used to verify the results of network pharmacology. Experimental verification of Yunshi Ganmao Heji for the intervention of RSV infection: A mouse model of RSV infection was established through intranasal infection. After the administration of Yunshi Ganmao Heji, blood routine test results, lung indexes and pathological changes in lung tissue were analyzed. Peripheral blood T cell subsets were detected by flow cytometry. The levels of TNF-α, IL-6 and IL-1β in serum were detected by ELISA. RT-PCR was used to detect the relative expression of TLR4, NF-κB and RSV-N gene at mRNA level in lung tissues.Results:A total of 41 active ingredients of Yunshi Ganmao Heji and 111 drug targets for RSV infection were obtained. Besides, 167 signaling pathways mainly including PI3K/AKT, MAPK and Toll-like receptor signaling pathways were obtained. Molecular docking results showed that the binding energies of luteotin, kaempferol and quercetin, three active ingredients of Yunshi Ganmao Heji, with RSV-G, RSV-F, PI3K, AKT1 and Bcl-2 were less than 0 kcal/mol. In vivo experiment results showed that compared with RSV group, the counts of white blood cells and lymphocytes increased and the lung index decreased in high-dose Yunshi Ganmao Heji group, with statistically significant difference ( P<0.05). HE staining showed pulmonary hyperplasia, thickened alveolar wall and inflammatory cell infiltration in interstitium in RSV group. Alveoli in ribavirin group as well as low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups tended to be of uniform size, and the alveolar walls was roughly uniform in thickness. Compared with RSV group, the low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups showed significantly increased numbers of CD3 +, CD4 + and CD8 + T lymphocytes, decreased CD4 + /CD8 + T cell ratio, lower levels of TNF-α, IL-6, IL-1β in serum, and reduced viral load and inhibited expression of TLR4 and NF-κB at mRNA level in lung tissues ( P<0.05). Conclusions:Yunshi Ganmao Heji can regulate RSV infection by targeting multiple targets and pathways with several active ingredients. Its main functions are to alleviate pathological injury in lung tissues and reduce inflammatory response, and the possible mechanism underlying the antiviral functions may be related to its inhibitory effect on the activation of TLR4/NF-κB pathway.

Objective To establish a sensitive,accurate and simple method for the determination of methotrexate and methotrexate polyglutamates(MTXPG2 and MTXPG3)in human erythrocytes.Methods A dual three element gradient liquid chromatograph with a fluorescence detector was used,the C18-WP column(20 mm ×4 mm,5μm)was used as the online SPE column,and the Athena C18-WP column(150 mm x4.6 mm,3 μm)was used as the analytical column.Erythrocyte lysate was precipitated with zinc sulphate-10％formic acid methanol(100:90,v/v),and postcolumn photo-oxidation of MTXPGs to fluorescent analytes using H2O2.The fluorescence excitation wavelength was 274 nm,the emission wavelength was 470 nm,the column temperature was 40 ℃,and the injection volume was 100 μL.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.Results MTX,MTXPG2 and MTXPG3 had good linearity in the range of 12.5-400.0 nmol·L-1.The standard curve of MTX was y=763.8x-2 961.1(R2=0.999 5),and the extraction recovery rate was 60.7％-66.1％;the standard curve of MTXPG2 was y=1 017.8x-239.8(R2=0.998 4),and the extraction recovery rate was 67.2％-67.3％;the standard curve of MTXPG3 was y=1 069.1x-819.6(R2=0.999 4),the extraction recovery rate was 62.9％-70.1％.Intra-day precision RSD＜8.8％,inter-day precision RSD＜10.8％.Conclusion This method is accurate and reproducibility,and the online solid-phose extraction enrichment and separation of target compounds simplify the sample pretreatment steps,improve the analysis efficiency,and is suitable for detecting the concentration of MTX,MTXPG2 and MTXPG3 in erythrocytes of patients with rheumatoid arthritis.