Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of effects of total saponin fraction from Dioscorea Nipponica Makino (TSDN) on M1/M2 polarization of monocytes/macrophages and arachidonic acid (AA) pathway in rats with gouty arthritis (GA).@*METHODS@#Seventy-two Sprague Dawley rats were randomly divided into 4 groups (n=18 in each): normal, model, TSDN at 160 mg/kg, and celecoxib at 43.3 mg/kg. Monosodium urate crystal (MSU) was injected into the rats' ankle joints to induce an experimental GA model. Blood and tissue samples were collected on the 3rd, 5th, and 8th days of drug administration. Histopathological changes in the synovium of joints were observed via hematoxylin and eosin (HE) staining. The expression levels of arachidonic acid (AA) signaling pathway were assessed via real-time polymerase chain reaction (qPCR) and Western blot. Flow cytometry was used to determine the proportion of M1 and M2 macrophages in the peripheral blood. An enzyme-linked immunosorbent assay (ELISA) was used to detect interleukine (IL)-1 β, tumor necrosis factor-alpha (TNF-α), IL-4, IL-10, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4).@*RESULTS@#HE staining showed that TSDN improved the synovial tissue. qPCR and Western blot showed that on the 3rd, 5th and 8th days of drug administration, TSDN reduced the mRNA and protein expressions of cyclooxygenase (COX)2, microsomal prostaglandin E synthase-1 derived eicosanoids (mPGES-1), 5-lipoxygenase (5-LOX), recombinant human mothers against decapentaplegic homolog 3 (Smad3), nucleotide-binding oligomerization domain-like receptor protein 3 (NALP3), and inducible nitric oxide synthase (iNOS) in rats' ankle synovial tissues (P<0.01). TSDN decreased COX1 mRNA and protein expression on 3rd and 5th day of drug administration and raised it on the 8th day (both P<0.01). It lowered CD68 protein expression on days 3 (P<0.01), as well as mRNA and protein expression on days 5 and 8 (P<0.01). On the 3rd, 5th, and 8th days of drug administration, TSDN elevated the mRNA and protein expression of Arg1 and CD163 (P<0.01). Flow cytometry results showed that TSDN decreased the percentage of M1 macrophages while increasing the percentage of M2 in peripheral blood (P<0.05 or P<0.01). ELISA results showed that on the 3rd, 5th, and 8th days of drug administration, TSDN decreased serum levels of IL-1 β, TNF-α, and LTB4 (P<0.01), as well as PGE2 levels on days 3rd and 8th days (P<0.05 or P<0.01); on day 8 of administration, TSDN increased IL-4 serum levels and enhanced IL-10 contents on days 5 and 8 (P<0.05 or P<0.01).@*CONCLUSION@#The anti-inflammatory effect of TSDN on rats with GA may be achieved by influencing M1/M2 polarization through AA signaling pathway.

Optimization of Prescription of Lycii Fructus Polysaccharide Buccal Tablets by Central Composite Design-response Surface Methodology and Investigation of Its Immunomodulatory Effect / 中国实验方剂学杂志

Objective:To prepare Lycii Fructus polysaccharide buccal tablets and investigate its immunomodulatory effect. Method:Taking the appearance, taste, hardness and disintegration time of the tablets as comprehensive evaluation index, based on single factor tests, central composite design-response surface methodology was adopted to optimize the prescription of Lycii Fructus polysaccharide buccal tablets with mass ratio of dextrin to mannitol, mass ratio of cyclamate to malic acid and dosage of sodium carboxymethyl starch (CMS-Na) as factors. Kunming mice were randomly divided into 5 groups, namely the Lycii Fructus polysaccharide buccal tablets low (100 mg·kg-1·d-1), medium (200 mg·kg-1·d-1) and high (300 mg·kg-1·d-1) dose groups, the normal group (0.9% normal saline, 300 mg·kg-1·d-1) and the positive medicine group (Cinengsu group, 300 mg·kg-1·d-1). The immunomodulatory effect of the buccal tablets were investigated by calculating immune organ index, monocyte-macrophage phagocytic index, serum hemolysin antibody level, and the voix pedis thickness difference of delayed hypersensitivity (DTH) of mice. Result:Optimal prescription for the buccal tablets was 80% of Lycii Fructus extract, 11.5% of dextrin-mannitol (1.2:1), 1% of cyclamate-malic acid (1:1), 0.5% of cream essence, 6.5% of CMS-Na, 0.5% of magnesium stearate, and appropriate amount of 80% ethanol. Under the optimal condition, the hardness of the buccal tablets was 11.83 kg, its disintegration time was 13.21 min, both of which were in line with the relevant provisions of the 2015 edition of Chinese Pharmacopoeia, and the buccal tablets had good appearance and taste. Compared with the normal group, medium and high dose groups of Lycii Fructus polysaccharide buccal tablets significantly increased thymus index, spleen index and phagocytic index of mice (PPPPPConclusion:The formulation process of the buccal tablets optimized by central composite design-response surface methodology is stable and feasible, and Lycii Fructus polysaccharide buccal tablets can improve the immune regulation function of normal mice, and this study can provide experimental basis for the development, utilization and clinical application of Lycii Fructus and Lycii Fructus polysaccharides.

Efficacy, safety and prognostic factors of callispheres® drug-eluting bead-transarterial chemoembolization in patients with early and middle stage hepatocellular carcinoma / 第二军医大学学报

Objective To explore the efficacy, safety and prognostic factors of drug-eluting bead-transarterial chemoembolization (DEB-TACE) in treatment of the patients with early and middle stage hepatocellular carcinoma (HCC). Methods Twenty-six early and middle stage HCC patients receiving DEB-TACE treatment were enrolled in this prospective cohort study. Modified response evaluation criteria in solid tumors (mRECIST) was used to evaluate the efficacy of DEB-TACE treatment. The deadline for follow-up was Dec. 20, 2017, and the progression free survival (PFS) and overall survival (OS) were recorded. Multivariate logistic regression model and Cox proportional regression model were used to analyze the factors affecting the efficacy and prognosis. Results A total of 32 DEB-TACE treatment were performed in 26 patients. Treatment-related adverse events were recorded in 31 DEB-TACE treatments. Perioperative pain frequency was 15 times (48.4%), including mild pain 10 times (32.3%) and moderate pain 5 times (16.1%); and fever frequency was 10 times (32.3%) and gastrointestinal reaction was 5 times (16.1%). Within 3 months of DEB-TACE treatment, the overall response rate (ORR) was 65.4% (17/26), and disease control rate (DCR) was 84.6% (22/26). Compared with the patients with maximum diameter of tumors=50 mm, the patients with maximum diameter of tumors<50 mm had a significantly higher ORR (92.3% [12/13] vs 38.5% [5/13], P=0.013). Compared with the patients with Barcelona stage B, the patients with Barcelona stage A had a significantly higher ORR (81.3% [13/16] vs 40.0% [4/10], P=0.031). The follow-up ranged from 2.9 to 20.0 months (median 7.2 months), median PFS was 11.9 months (95% CI 5.0-18.9 months), and median OS was 14.6 months (95% CI 9.9-19.2 months). Multivariate logistic regression revealed that tumor maximum diameter=50 mm was an independent predictor of poor ORR (P=0.036). Cox proportional regression model analysis showed that no clinicopathological characteristics were independent predictors of PFS or OS. Conclusion DEB-TACE treatment is an effective and safe method for early and middle stage HCC patients, and maximum diameter of tumor=50 mm can be used as an independent prognostic biomarker.

Optimazation of preparation of syringopicrosides PLGA nanopartides by central composite design-response surface methodology / 中草药

Objective: To optimize the formulation of syringopicrosides poly (lactic-co-glycolic acid, PLGA) nanoparticles (Syr-NPs). Methods: Syr-NPs were prepared by nanoprecipitation method. The encapsulation efficiency (EE), drug loading (DL), average particle size and general evaluation "normalized value" were used as evaluation indexes. The central composite design was used to inspect the effects of the concentration of PLGA (A), the concentration of syringopicrosides (B), the ratio of aqueous phase to organic phase (C) on three evaluation indexes mentioned above and the "normalized value" ofgeneral evaluation. Prediction and analysis for selecting the best prescription condition were carried out by using the central composite design-response surface method. Results: The concentration of PLGA, the concentration of syringopicrosides and the ratio of aqueous phase to organic phase according to the optimized prescription were 9.63 mg/mL, 12.88 mg/mL and 1:9.46, respectively; And the EE, drug loading and average particle diameter of Syr-NPs prepared according to the optimized prescription were (27.86 ± 0.87)%, (7.02 ± 0.15)%, and (110.0 ± 1.20) nm, respectively. Conclusion: This method is stable and feasible and can be used to optimize the formulation and preparation process of syringopicrosides wrapped inside with PLGA nanoparticles.