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 study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells,plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province,explore the distribution of monitoring values and the change of monitoring level,so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei.Methods In 2023,the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected,scatter plots were made and the range markers were set,and the"mean±SD"line was taken as the upper limit and lower limit of the measurement range.In 2024,the monitoring values in 2023 were added,and the changes of two measurement ranges were compared to analyze the stability and overall level.Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin,washed erythrocyte-hemoglobin,washed erythrocyte-su-pernatant protein,cryoprecipitate coagulation factor-FⅧ,fresh frozen plasma-FⅧ,leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993,6.252 to 6.104,0.273 to 0.267,57.506 to 56.276,0.920 to 0.892,0.653 to 0.644 and 2.653 to 2.603,respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced disper-sion.Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells,hemoglobin content of the wash eryth-rocyte,protein content of supernatant of the wash erythrocyte,hemolysis rate of the wash erythrocyte,FⅧ content of the cryoprecipitate coagulation factor,plasma protein content of the fresh frozen plasma,FⅧ content of the fresh frozen plasma,platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476,44.915 to 44.861,0.280 to 0.283,0.137 to 0.142,133.989 to 133.271,60.262 to 60.208,1.301 to 1.277 and 3.036 to 3.033,respectively,and was closer to the national standard line,which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023.The long-term qualified rate of coagulation items was low,and no improvement has been ob-served.The stability of biochemical items has been enhanced but overall deviation has occurred,with the average value close to the national standard line.The possibility of subsequent testing failure has increased.The counting items showed no obvi-ous common characteristics.Conclusion The use of"mean±SD"in the analysis can visually display the distribution of mo-nitoring values of different items in Hebei,forming an indicator measurement range covering the past nine years.It shows the characteristics of each item,and provides reference for subsequent quality control laboratory data analysis of each blood sta-tions to takes active measures to improve the monitoring level.

Objective:To explore the pathogenesis and potential biomarkers of atrial fibrillation based on bioinformatics.Methods:Differentially expressed genes and module genes related to atrial fibrillation were obtained from GSE41177 and GSE79768 datasets(Chinese-origin tissue samples)through differential expression analysis and weighted gene co-expression network analysis.Candidate hub genes were obtained by taking intersections,and hub genes were obtained after gender stratification.Subsequently,functional enrichment analysis and immune infiltration analysis were performed.Four machine learning models were constructed based on the hub genes,and the optimal model was selected to construct a prediction nomogram.The prediction ability of the nomogram was verified using calibration curves and decision curves.Finally,potential therapeutic drugs for atrial fibrillation were screened from the DGIdb database.Results:A total of 67 differentially expressed genes and 65 module genes related to atrial fibrillation were identified.Functional enrichment analysis indicated that the pathogenesis of atrial fibrillation was closely related to inflammatory response,immune response,and immune and infectious diseases.Four common hub genes(TYROBP,FCER1G,EVI2B and SOD2),and two genes specifically expressed in male(PILRA and SLC35G3)and female(HLA-DRA and GATP)patients with atrial fibrillation were obtained after gender-segregated screening.The extreme gradient boosting model had satisfactory diagnostic efficiency,and the nomogram constructed based on the hub genes,male significant variables(PILRA,SLC35G3 and SOD2),and female significant variables(FCER1G,SOD2 and TYRO BP)had satisfactory predictive ability.Immune infiltration analysis demonstrated a disturbed immune infiltration microenvironment in atrial fibrillation with a higher abundance of plasma cells,neutrophils,and γδT cells,with a higher abundance of neutrophils in males and resting mast cells in females.Two potential drugs for the treatment of atrial fibrillation,valproic acid and methotrexate,were obtained by database and literature screening.Conclusions:The pathogenesis of atrial fibrillation is closely related to inflammation and immune response,and the microenvironment of immune cell infiltration of cardiomyocytes in the atrial tissue of patients with atrial fibrillation is disordered.TYROBP,FCER1G,EVI2B and SOD2 serve as potential diagnostic biomarkers of atrial fibrillation;PILRA and SLC35G3 serve as potential specific diagnostic biomarkers of atrial fibrillation in the male population,which can effectively predict the risk of atrial fibrillation development and are also potential targets for the treatment of atrial fibrillation.

OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

Background::Accurately and efficiently extracting microbial genomic sequences from complex metagenomic data is crucial for advancing our understanding in fields such as clinical diagnostics, environmental microbiology, and biodiversity. As sequencing technologies evolve, this task becomes increasingly challenging due to the intricate nature of microbial communities and the vast amount of data generated. Especially in intensive care units (ICUs), infections caused by antibiotic-resistant bacteria are increasingly prevalent among critically ill patients, significantly impacting the effectiveness of treatments and patient prognoses. Therefore, obtaining timely and accurate information about infectious pathogens is of paramount importance for the treatment of patients with severe infections, which enables precisely targeted anti-infection therapies, and a tool that can extract microbial genomic sequences from metagenomic dataset would be of help.Methods::We developed MetaGeneMiner to help with retrieving specific microbial genomic sequences from metagenomes using a k-mer-based approach. It facilitates the rapid and accurate identification and analysis of pathogens. The tool is designed to be user-friendly and efficient on standard personal computers, allowing its use across a wide variety of settings. We validated MetaGeneMiner using eight metagenomic samples from ICU patients, which demonstrated its efficiency and accuracy.Results::The software extensively retrieved coding sequences of pathogens Acinetobacter baumannii and herpes simplex virus type 1 and detected a variety of resistance genes. All documentation and source codes for MetaGeneMiner are freely available at https://gitee.com/sculab/MetaGeneMiner. Conclusions::It is foreseeable that MetaGeneMiner possesses the potential for applications across multiple domains, including clinical diagnostics, environmental microbiology, gut microbiome research, as well as biodiversity and conservation biology. Particularly in ICU settings, MetaGeneMiner introduces a novel, rapid, and precise method for diagnosing and treating infections in critically ill patients. This tool is capable of efficiently identifying infectious pathogens, guiding personalized and precise treatment strategies, and monitoring the development of antibiotic resistance, significantly impacting the diagnosis and treatment of severe infections.