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BACKGROUND:In clinical practice,Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis,but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis. OBJECTIVE:Based on network pharmacology and molecular docking technology,to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis,providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components. METHODS:Utilizing traditional Chinese medicine research platforms,traditional Chinese medicine encyclopedias,and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic,effective ingredients were retrieved and identified.3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction.Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank,GeneCards,and OMIM.The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database.A protein-protein interaction network graph was constructed using the STRING platform.Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization.A four-layered network model of traditional Chinese medicine,ingredients,targets,diseases,and pathways was constructed using Cytoscape 3.9.0.The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets.A type II collagen+adjuvant-induced arthritis rat model was established,and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after 21 days of intervention. RESULTS AND CONCLUSION:A total of 28 active ingredients from Cibotium barometz and Epimedium were selected,yielding 288 intersection targets for rheumatoid arthritis.The main ingredients included isobavachalcone,cibotium,and epimedium.The main targets included protein kinase 1 for serine/threonine(AKT1),tumor necrosis factor,and vascular endothelial growth factor A.Gene ontology analysis yielded 2 232 biological processes,mainly related to serine protein phosphorylation,positive regulation of serine/threonine protein kinase,and reactive oxygen metabolism.Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 202 pathways,mainly involving the PI3K/AKT signaling pathway and epidermal growth factor receptor signaling pathway,which may exert therapeutic effects by regulating synovial cell apoptosis and proliferation and suppressing inflammatory factors.Molecular docking results showed the strongest binding activity and stable structure of Cibotium barometz and Epimedium with AKT1 and estrogen receptor transcription factor 1,which was closely related to apoptosis and proliferation and inflammatory signaling pathways such as PI3K/AKT.Cibotium barometz and Epimedium reduced the expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the serum of collagen-induced arthritis rat models.Cibotium barometz and Epimedium reduced the expression of p-PI3K,p-AKT,and p-FOXO1 in the synovium of collagen-induced arthritis rat models.The results indicate that the combination of Cibotium barometz and Epimedium may exert therapeutic effects by inhibiting the proliferation of synovial cells and suppressing the expression of inflammatory factors via the PI3K/AKT/FOXO1 signaling pathway.This may be closely related to the occurrence of inflammation and bone destruction in rheumatoid arthritis,and provides a reference for the rational use and development of new drugs in clinical practice.
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This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.
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Ratas , Animales , Agua , Ratas Sprague-Dawley , Hígado , FN-kappa B , Cirrosis Hepática , Ácidos y Sales Biliares , Peso Corporal , ARN MensajeroRESUMEN
Objective:To investigate the efficacy and safety of peritoneal dialysis (PD) in end-stage renal disease (ESRD) patients with liver cirrhosis (LC).Methods:Clinical data of PD patients receiving regular treatment followed up for≥6 months, and aged≥18 years in the Third Affiliated Hospital of Hebei Medical University Peritoneal Dialysis Center from January 1, 2013 to March 31, 2020 were retrospectively collected. The patients were divided into LC-PD group and non-LC-PD group according to whether they had LC or not. Propensity score matching (PSM) was used to match the LC-PD group and the non-LC-PD group with 1∶4 ratio. The baseline clinical data, dialysis adequacy, peritonitis and clinical outcomes between the two groups were compared. Kaplan-Meier survival curve and Log-rank test were used to compare the survival rate and technical survival rate between the two groups.Results:A total of 241 PD patients were included in this study. After PSM, 13 cases in LC-PD group and 52 cases in non-LC-PD group were included. Compared with non-LC-PD group, patients in LC-PD group had lower baseline urine volume ( Z=-3.546, P<0.001) and serum albumin ( Z=-2.609, P=0.009). At the follow-up of 3, 6, 12 and 24 months, total serum protein ( t=-3.319, P=0.002), serum albumin ( t=-4.019, P<0.001), triglyceride ( Z=-2.263, P=0.024), and serum phosphorus ( Z=-2.173, P=0.030) in the LC-PD group were lower than those in non-LC-PD group. During the follow-up period of 2 years, the patients in the LC-PD group had significantly higher serum albumin than baseline values ( χ2=16.901, P=0.001), and there was no statistically significant difference between the two groups ( χ2=0.155, P=0.694). The decline rate of residual kidney Kt/V in the LC-PD group was slower than that in the non-LC-PD group ( χ2=44.589, P<0.001). The incidence of peritonitis in LC-PD group was higher than that in the non-LC-PD group, with a statistically significant difference (0.59/patient-year vs 0.20/patient-year, Z=-2.135, P=0.033). The composition ratio of pathogenic bacteria in both groups was mainly gram-positive bacteria (10/25 vs 11/30) and proportion of Streptococcus in LC-PD group was higher than that in non-LC-PD group (4/10 vs 0/11, P=0.035). The proportion of Escherichia coli in the first peritonitis was higher than that in LC-PD group (4/9 vs 1/22, P=0.017). The Kaplan-Meier survival curve results showed no statistically significant difference in survival rate (Log-rank χ2=0.491, P=0.484) and technical survival rate (Log-rank χ2=0.408, P=0.523) between the two groups. Conclusions:PD is a safe and effective treatment mode for ESRD patients with LC, and the survival rate and technical survival rate are comparable to those patients without LC. The incidence of peritonitis in patients with LC-PD in our dialysis center is higher than that in the non-LC-PD patients, and gram-positive bacterial infections are the mainstay, suggesting that attention should be paid to strengthening patient management and training.
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Objective To conduct the contrastive analysis on the indwelling time of fixing indwelling needle by cutting sterile transparent dressing and non-cutting sterile transparent dressing.Methods A total of 236 inpatients in this hospital from August to December 2016 were selected.The patients with odd at last number of admission number served as the experimental group (119 cases),while the patients with even at the last number of admission number served as the control group(117 cases).The indwelling needle type was 18GA,the puncture was once success and the fluid infusion course was more than 5 d.The experimental group used the cutting sterile transparent dressing for fixing the indwelling needle and the extension tube vas completely exposed to the outside of dressing,while the control group adopted the conventional indwelling needle application fixation mode.The blood returning plugging pipe rate,average indwelling time and phlebitis occurrence at 24,48,72,96,＞ 96 h after indwelling needle were recorded.Results The blood returning plugging tube situation at 48,72,96,＞96 h after indwelling needle in the experimental group was superior to that in the control group,the difference was statistically significant(P＜0.05);the average indwelling time in the experimental group was (72.12 ± 3.25)h,while which in the control group was (59.34--3.78) h,and the difference was statistically significant (P＜0.05).Seven cases of phlebitis occurred in the experimental group and 9 cases in the control group,the difference was not statistically significant(P＞0.05).Conclusion Applying cutting sterile transparent dressing for fixing the indwelling needle reduces the plugging pipe rate due to returning blood coagulation,extends the indwelling needle use time,increase the patient's satisfaction,moreover does not increase the phlebitis occurrence risk.
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Objective To explore the mechanism that Staphylococcus aureus(S.aureus) α-toxin(Hla) regulate miR-142 expression and inhibit macrophage phagocytosis.Methods BALB/C mice and RAW264.7 cells were infected with wild type S.aureus(WT S.aureus),Hla deletion S.aureus(△HlaS.aureus) or phosphate buffered saline(PBS),and the expression level of miR-142 of skin tissues and cells were detected.miR-142 mimics and inhibitor were then applied in the RAW264.7 culture to examine the effect on phagocytosis.Direct targeting of miR-142 on protein kinase Cα(PKCα) was assessed by luciferase assay and western blotting.Results miR-142 expression in △HlaS.aureus group were significantly down-regulated than WT S.aureus group(P<0.05).MiR-142 mimics inhibited RAW264.7 phagocytosis ability and inhibitor enhanced RAW264.7 phagocytosis ability.PKCα was directly targeted by miR-142.MiR-142 mimics significantly decreased the mRNA expression levels of PKCα in RAW264.7 cells(P<0.05).Conclusion Hla could promote miR-142 expression in macrophages.MiR-142 could inhibit macrophage phagocytosis through down-regulated PKCα.
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Objective To analyze the nutritional status of patients with continuous ambulatory peritoneal dialysis and explore reasonable and effective nursing measures.Methods Nutritional assessment was performed in 60 patients with continuous ambulatory peritoneal dialysis,using subjective integrated nutritional assessment,dietary analysis,measurement of biochemical indexes of the human body to analyze the factors that might affect the nutritional status of patients.Results 60 cases of malnutrition occurrd in 20 patients (33.3per cent),mainly due to insufficient protein and energy intake,inadequate dialysis,peritoneal inflammation,metabolic acidosis,psychosocial factors and not using erythropoietin,and so on.Conclusions Measures such as emphasis paid to malnutrition status of continuous ambulatory peritoneal dialysis patients,giving guidance of rational diet,performing full implementation of nursing measures according to the related factors,can improve the nutritional status of patients and improve patients' quality of life.