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Objective:To investigate the potential mechanism of Shenfu injection in regulating stress response via the neuro-endocrine-immune system by network pharmacology and molecular docking. Methods:The main active ingredients and related targets of Shenfu injection were screened using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform.PharmMapper, Swiss Target Prediction platform and Uniprot database were used to predict the target and unify the gene names.GeneCards, OMIM, TTD, CTD, Drugbank, Disgenet and Pharmgkb databases were searched to screen the related targets regulated by stress responses.Venny 2.1 tool was used to obtain the potential effect targets of the intersection between Shenfu injection and stress response regulation, and the STRING database was imported to construct the interaction PPI network and screen the key targets.Potential effect targets were uploaded to Metascape database online analysis for study on the mechanism through GO and KEGG enrichment analysis.Autoduck and Pymol were used for molecular docking and visualization.Results:Forty-three main active ingredients and 257 related targets for Shenfu injection were obtained by component screening and target prediction.A total of 4 811 targets related to stress response regulation were retrieved from the database, 188 potential effect targets were obtained by intersection with Shenfu injection component-related targets, and 14 key targets were obtained by PPI network screening.Eighteen samples were screened by GO enrichment analysis, which mainly involved the circulatory system and humoral regulation, responses to external stimuli and trauma, MAPK cascade reaction, postsynaptic membrane, receptor complex and ion channel complex and neurotransmitter receptor activity, etc.KEGG enrichment analysis showed 20 highly correlated pathways, mainly covering neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling, steroid hormone biosynthesis, IL-17, TNF, MAPK, cGMP-PKG, PI3K-Akt, NF-κB, Toll-like receptor signaling pathway and cell apoptosis, etc.The results of molecular docking indicated that the main active components had good binding force with the key target.Conclusions:The components of Shenfu injection such as kaempferol, β-sitosterol, Demethyldelavaine, Stigmasterol, ginsenoside, Carnosifloside, hypaconitine may act on targets such as AKT1, TNF, IL1B, PTGS2, HSP90AA1, MAPK1, NFKBIA, NR3C1 and ADRB2 and regulate the stress response through the mechanisms such as regulation of the functional state of the neuro-endocrino-immune system, inhibition of inflammatory responses, anti-oxidative stress and reduction of cell apoptosis.
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OBJECTIVE： To provide reference for rational use of estradiol （E2） preparation in clinic. METHODS： The medical records of outpatients receiving assisted reproductive technology （ART） and E2 preparation [Estradiol valerate tablets （EV）， Complex packing estradiol tablets/estradiol and dydrogesterone tablets （EP）， Estradiol gel （EG）] were collected from the reproductive medicine center of a hospital during Jan. 2016-Mar. 2017. Taking drug instruction as standard， the rationality of medical records was evaluated from aspects of indication， route of administration， contraindication， usage and dosage， treatment course， etc. At the same time， these patients were followed up by telephone or outpatient service， and their pregnancy outcomes and ADR were summarized. RESULTS： A total of 12 646 prescriptions were collected， and 7 222， 3 912， 181 and 1 331 prescriptions used EV， EP， EG and EV+EP， respectively. The types of off-label use included over-indication， over-route and over-contraindication， and the rates of off-label use rates were 100％， 11.73％ and 43.60％， respectively. A total of 5 868 ART patients were involved； 439 patients received fresh embryo transplantation， and 5 429 patients received frozen-thawed embryo transplantation， involving 720 and 11 926 prescriptions， respectively. The rates of off-label use of above E2 preparations were 100％ （except for fresh embryo transplantation patients using EG）. As of Feb. 2018， the infant-holding rates of ART patients using EV， EP， EG and EV+EP were 85.29％， 85.37％， 86.36％ and 85.45％， respectively. No relevant ADR and neonatal birth defect was found. CONCLUSIONS： The phenomenon of off-label use of E2 preparations is widespread in the reproductive medicine center of the hospital. Although there is no indication of related safety risks， evidence-based evaluation should be carried out by enlarging the sample size in clinical practice， and careful use.
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Objective To investigate the role of mitochondrial KATP (mito-KATP) channel in reduction of renal ischemia-repeerfusion (I/R) injury by ischemic postconditioning (IPo) in rats. Methods Thirty-five adult male SD rats weighing 250-280 g were randomly divided into 5 groups ( n = 7 each): group Ⅰ sham operation (group S); group Ⅱ I/R; group Ⅲ IPo; group Ⅳ 5-HD + I/R and group V 5-HD + IPo. The rats were anesthetized with intraperitoneal (IP) chloral hydrate 300 mg/kg. Bilateral kidneys were exposed and their pedicles were occluded for 45 min with atraumatic mini-clamp followed by 6 h reperfusion in group Ⅱ - Ⅴ . In group Ⅲ and Ⅴ 3 cycles of 10 s reperfusion followed by 10 s ischemia were applied immediately after 45 min kidney ischemia. In group Ⅳ and Ⅴ 5-HD (a specific blocker of the mito-KATP channel) 10 mg/kg was given IP at 30 min before ischemia. Blood samples were obtained at 6 h of reperfusion for determination of serum creatinine (Cr) and urea nitrogen (BUN) concentrations. The animals were then killed. Bilateral kidneys were removed for determination of mitochondrial membrane potential in the renal tubular epidural cell and intracellular reactive oxygen species (ROS)content and free Ca2+ concentrations. Results Renal I/R significantly increased serum Cr and BUN concentrations and intracellular free Ca2+ concentration and ROC content and decreased mitochondrial membrane potential as compared with sham operation group. IPo significantly attenuated the I/R-induced changes mentioned above. The protective effects of IPo against renal I/R injury was reversed by 5-HD. Conclusion Mito-KATP channel is involved in reduction of I/R-induced renal injury by ischemic postconditioning.