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ObjectiveThis study aimed to predict the pharmacodynamic material basis and core targets of Bailing capsules in the treatment of chronic obstructive pulmonary disease （COPD） based on network pharmacology and molecular docking， which were further verified by cell experiments to explore the mechanism. MethodThe main active ingredients and related targets of Bailing capsules were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction. The main COPD targets were searched from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM） and Therapeutic Target Database （TTD）. The protein-protein interaction （PPI） network was constructed by STRING and Cytoscape 3.6.1. Gene Ontology （GO） function annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed by the Database for Annotation， Visualization and Integrated Discovery （DAVID）. Molecular docking verification was carried out using AutoDock Vina. The cell viability was detected by 3-（4，5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium （MTS） assay， and the mRNA level of the targets was detected by real-time polymerase chain reaction （Real-time PCR）. ResultA total of 11 active ingredients of Bailing capsules such as cerevisterol， 270 related drug targets， and 1 020 COPD target proteins were obtained， with 74 intersection targets. The visualization analysis of the PPI network showed that the core targets of Bailing capsules in the treatment of COPD were tumor protein P53 （TP53）， catenin beta 1 （CTNNB1）， tumor necrosis factor （TNF）， interleukin-6 （IL-6） and insulin （INS）. Further， 20 signaling pathways were screened by KEGG enrichment analysis as the main pathways for Bailing capsules to treat COPD， involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， cyclic adenosine monophosphate （cAMP）， forkhead box O （FoxO）， TNF， and hypoxia inducible factor-1 （HIF-1） signaling pathways. Molecular docking validation demonstrated that four active ingredients had stable binding to IL-6， with the lowest energy. Bailing capsules could reduce the mRNA level of IL-6 in RAW264.7 cells induced by lipopolysaccharide （LPS） （P<0.01） compared with the control group. ConclusionThe pharmacological mechanism of Bailing capsules in the treatment of COPD might be that its main active ingredients improved the inflammatory response by acting on TP53， CTNNB1， TNF， IL-6 and other targets and regulating PI3K/Akt， cAMP and other signaling pathways， thereby ameliorating COPD symptoms. This study provided experimental basis for subsequent in-depth research， and provided a diagnosis and treatment direction for disease-related clinical treatment.
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Objective:To investigate the safety and efficacy of low molecular weight heparin (LMWH) bridging program in the perioperative period of mini-percutaneous nephrolithotomy (mPCNL) for long-term antithrombotic patients.Methods:The clinical data of 50 patients who received long-term antithrombotic therapy with mPCNL in Sun Yat-sen Memorial Hospital from January 2013 to December 2017 were retrospectively analyzed. Perioperative anticoagulation plans were drawn up after discussion with an internist. Patients with high thrombosis risk were bridged with LMWH during the perioperative period. Resumed LMWH anticoagulation within 48 hours after surgery. Patients with low or medium thrombosis risk directly discontinued anticoagulation one week before surgery. Preoperative anticoagulation was resumed within 48 hours after removing the nephrostomy tube in all patients. We analyzed the general information before surgery, data during surgery, postoperative hemoglobin changes and stone-free rate (SRF) of all cases. 21 patients were treated with LMWH bridging (bridging group), and 29 patients were directly discontinued with anticoagulant drugs (non-bridging group). There was no statistical difference between the two groups in age [(59.7±7.1) vs. (52.4±10.4)years] , gender [(male/female), 14/7 vs. 19/10], BMI [ (24.3±3.9) kg/m 2 vs. (24.7±5.1) kg/m 2], S. T.O.N.E. score (7.4±1.1 vs. 6.9±1.0), stone surface area [ 314.0(31.4-1 130.4) mm 2 vs. 282.5(64.7-866.0) mm 2], the number of calculi involved in calyces (6/15 vs. 13/16) and stone-related surgical history [ 34% (7/21) vs. 24% (7/29) ]. Results:In the bridging group, 18 patients (86%) performed single-channel mPCNL, 3 patients (14%) underwent dual-channel mPCNL, and the operation time was 80 (35-180) min. In the non-bridging group, 27 patients (93%) underwent single-channel mPCNL, 2 patients (7%) performed dual-channel mPCNL, and the operation time was 80 (30-60) min. The mean changes in hemoglobin in the bridging group and the non-bridging group was 18 (-2 -66) g/L and 14 (-25-64) g/L, respectively ( P = 0.073). The average postoperative hospital stay in the bridging group was (8.6 ± 3.5) days, and the non-bridging group was (7.1 ± 2.3) days ( P= 0.057). Two patients in each group received blood transfusion, and no patients received interventional embolization. The SRF of bridging group and non-bridging group was 81.0% (17/21) vs. 75.9% (22/29) ( P = 0.67) 1 month after the operation. During the perioperative period, no patients had thrombotic complications. Conclusions:When mPCNL was required for long-term antithrombotic treatment patients, the use of LWMH alternatives during the perioperative period did not increase bleeding related complications.
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Objective To investigate the effects of magnesium sulfate and magnesium L-sulfonate on the neurobehavioral response and the expression of induced nitric oxide synthase (iNOS) in neurons after acute cerebral ischemia in rats. Methods One hundred and twelve male Sprague-Dawley ( SD) rats were double-blinded randomly divided into sham-operated group, middle cerebral artery occlusion ( MCAO ) group,MgSO4 treatment group,L-MgT treatment group. Each group was further divided into 6 h,12 h and 24 h subgroups according to the different detection time points. Rat MCAO models were produced following the Longa's method. And the Longa score,limb-placing test,rotarod test,and sticky tape test were performed to evaluate the neurological damage,autonomous movement and coordinate perception in the 24 h subgroup. At the end of the experiment,2,3,5-triphenyltetrazolium chloride ( TTC) was used to evaluate the area of cerebral infarction at 24 h reperfusion. Immunohistochemical staining was employed to determine the altera-tions in iNOS expression in neurons 6 h,12 h and 24 h after reperfusion. Results In behavioral evaluation:Longa score:Normal performance was observed in sham-operated group. Compared with the MCAO group,the scores of MgSO4 treatment group(1. 71±0. 18) and L-MgT treatment group(1. 14±0. 14) were decreased (t=0. 548,3. 873,all P<0. 05),and the score of L-MgT treatment group was lower than that of the MgSO4 group(t=2. 828,P<0. 05). Limb symmetry score:There was no statistically significant difference between MgSO4 group and MCAO group,but there was a statistically significant difference between L-MgT group and MCAO group (t=7. 071,P<0. 05). The roding experiment:The time of MgSO4 group and the L-MgT group were significantly different from that of the MCAO group (t=9. 588,20. 776,P<0. 05),and the time of the L-MgT group was significantly higher than that of the MgSO4 group (t=4. 983,P<0. 05). The right limb strip removal experiment: The time of MgSO4 group and L-MgT group were statistically different from that of MCAO group (t=6. 135,5. 825,P<0. 05),and the time of L-MgT group was increased compared with that of MgSO4 group(t=4. 507,P<0. 05). TTC test:No infarction was formed in the sham group. Compared with MCAO group ((36. 82±1. 35)%),the cerebral infarction volume of MgSO4 group ((17. 39±1. 72)%) and L-MgT group ((10. 81 ± 1. 35)%) significantly decreased, with statistically significant differences ( t=8. 874,11. 105,P<0. 05). Compared with MgSO4 group,cerebral infarction volume in L-MgT group was sig-nificantly reduced,with statistical significance (t=2. 593,P<0. 05). HE staining:There was no statistically significant difference in cell morphology between MgSO4 group and MCAO group at each time point,but the cell morphology of L-MgT group was intact compared with that of MCAO group. INOS staining at 24 h:There was no statistically significant difference in the positive cell density between the MgSO4 group and the MCAO group,but the L-MgT group (cortex:(196. 7±8. 1);striatum:(153. 3±3. 8)) positive cell density was lower than that of the MCAO group (cortex:(375. 0±6. 7),striatum:(358. 3±4. 5)),and the difference was sta-tistically significant (t=11. 113,36. 231,P<0. 05). Conclusion L-MgT may have a significantly protective effect on MCAO rats,and its mechanism may be related to the level of iNOS in neurons.