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).

[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

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.

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 evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Abstract Glutamate receptors are widely distributed in the central nervous system(CNS) and participate in the delivery of excitatory neurotransmitters, including ionotropic glutamate receptors and metabotropic glutamate receptors. Metabotropic glutamate receptors(mGluRs) regulate neuronal excitability and synaptic plasticity, and are classified into group Ⅰ, Ⅱ and Ⅲ. The roles of group Ⅰ mGluRs in psychiatric and neurodegenerative diseases have been extensively studied, especially in the pathological progression of acute brain injury. Several studies have shown that group Ⅰ mGluRs can be involved in eliminating inflammatory damage, suppressing cell apoptosis, regulating neural network disorders, and promoting brain function recovery after acute brain injury. Therefore, group Ⅰ mGluRs have the potential to be effective targets for the treatment of acute brain injury. This paper reviews the distribution and function of group Ⅰ mGluRs in CNS, the pathological role in acute brain injury, and explore the potential of the development of drugs targeting group Ⅰ mGluRs.

ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg^-1）， medium-dose Danggui Niantongtang group （1.638 g·kg^-1）， high-dose Danggui Niantongtang group （3.276 g·kg^-1）， and Meloxicam group （0.975 mg·kg^-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.

Abstract: Integrated stress response is an adaptive response produced by eukaryotic cells after intracellular and extracellular stimulation. The activation of integrated stress response inhibits the translation of most proteins, yet it can promote the translation of certain proteins to cope with complex cellular microenvironment changes. A large number of studies have found that in a variety of nervous system diseases, the integrated stress response can be activated by stress signals of disease-related cells and participates in the occurrence and progression of diseases through processes such as learning and memory consolidation, myelin regeneration and synaptic plasticity. This article summarizes the role, mechanism and possible drug targets of integrated stress response in central nervous system diseases and discusses the potential of pharmacological methods to regulate integrated stress response in the treatment of central nervous system diseases, in order to provide reference for pathological research on and drug development for central nervous system diseases.

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.