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OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments, but its side effects often limit the clinical usage. Metabolic disorders are one of the side effects induced by cisplatin, which closely relate to the onset of chemotherapy-induced anorexia (CIA) in cancer patients but lacks effective controls. Liujunzi decoction (LJZD) is a traditional Chinese formula that has a promising effect in treating CIA. However, whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow. The present study evalu?ated the mechanism of cisplatin-induced metabolic disorders, and the effect of LJZD in ameliorating these disturbances. METHODS 42 male Sprague-Dawley (SD) rats (180-220 g) were randomly divided into 3 groups:normal control group (distilled water+saline), model group (distilled water+cisplatin), LJZD group (4.8 g·kg-1 Liujunzi decoction ingredients+cisplatin). Intragastrical administered each drug twice a day (7:00-19:00) since day 0 for 4 d, animals were intraperito?neal injected with cisplatin 6 mg·kg-11 h after administration while normal control groups were injected with same volume of saline. On day 3, each group was anesthetized with pentobarbital sodium 45 mg · kg-1 (ip), and blood samples were collected from aorta abdominalis. Then the samples were analyzed using an LC-ESI-MS/MS system. Significantly regu?lated metabolites between groups were determined by VIP≥1 and absolute Log2FC (fold change)≥1. Identified metabo?lites were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Metaboanalyst 5.0 (https://www.metaboanalyst.ca/). RESULTS A total of 133, 77 and 32 differential metabolites were filtrated in control vs model, control vs LJZD and model vs LJZD groups respectively. Comparing to control, the levels of hexadecanoic acid (Log2FC=6.3153), linoleic acid (Log2FC=5.3478), and 8, 11-icosadienoic acid (Log2FC=5.2342) significantly increased, and the levels of N-acetyl-L-tyrosine (Log2FC = -2.6283), cinnamic acid (Log2FC = -2.3381), N-acetylphenylalanine (Log2FC = -2.2501) significantly decreased in model group. The KEGG pathway enrichments of these metabolites indi?cated that, cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid, unsaturated fatty acids, and phenylalanine. Compared to control, treatment of LJZD significantly increased the levels of 4-hydroxytryptamine (Log2FC =12.0186), hexadecanoic acid (Log2FC = 5.7412), linoleic acid (Log2FC = 5.1877) and significantly decreased the levels of N-acetylmethionine (Log2FC=-1.7317), 2-aminoethanesulfinic acid (Log2FC=-1.6578), N-acetyl-L-tyrosine (Log2FC=-1.5355). And com?paring to the model group, 4-hydroxytryptamine (Log2FC = 12.0186), 7, 12-diketocholic acid (Log2FC = 2.0998), N-acetylneuraminic acid (Log2FC = 2.0560) markedly increased, and 3-hydroxy-3-methylpentane-1 (Log2FC = -1.9202), 5-dioic acid (Log2FC = -1.7166), N-isovaleroylglycine, hexanoyl glycine (Log2FC = -1.4958) markedly decreased in LJZD group. It was worth noting that, there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups, which were the key metabolites of LJZD in treating CIA. Among these 23 common metabolites, there were 16 metabolites excluding the control vs LJZD group, that was, LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites. Cisplatin-induced downregula?tion of 11 metabolites such as hydrocinnamic acid, (±)12(13)epoxy-9Z-octadecenoic acid, cinnamic acid were upregulated after LJZD treatment, and cisplatin-induced upregulation of imidazoleacetic acid, 2'-deoxycytidine-5'-monophosphate and other 5 metabolites were downregulated by LJZD. The KEGG pathway analysis indicated that the linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism were the most enriched metabolic pathway. Thus, cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism, and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA. CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabo?lism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments, relating to the regulation of linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism.
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Objective To study the differentiation types of microglia induced by macrophage colony-stimulating factor (M-CSF).Methods Rat microglia cultured in vitro were inoculated on 6-well plates and divided into 3 groups (n=4 each) using a random number table method when cell confluence reached 70％:blank control group (C group),vehicle control group (P group) and M-CSF group.Group P was incubated with phosphate buffer solution for 7 days and group M-CSF with 20 ng/ml M-CSF for 7 days.The expression of a specific M1 phenotype marker tumor necrosis factor-alpha (TNF-α) and specific M2 phenotype markers interleukin-10 (IL-10) and brain-derived neurotrophic factor (BDNF) was determined by Western blot.Results Compared with C group,the expression of IL-10 and BDNF was significantly upregulated (P＜0.05),and no significant change was found in TNF-α expression in M group (P＞0.05),and no significant change was found in the expression of TNF-α,IL-10 or BDNF in P group (P＞0.05).Conclusion M-CSF can induce microglia to differentiate into a M2 phenotype.
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BACKGROUND:Hydroxyapatite is the main mineral component of bone and teeth.It is non-immunogenic and osteoinductive and suitable for bone repair.Strontium and calcium are cognate elements in the periodic table of elements and it has been proved that strontium has dual effects,namely,osteogenic promotion and suppression of osteoclast activity.OBJECTIVE:To summarize the preparation of strontium-substituted hydroxyapatite and its biological properties.METHODS:The first author searched the PubMed database for related literature from 1990 to 2017.The key words were "strontium;substituted;doped;containing;hydroxyapatite".The literatures obtained were screened,and the irrelevant and repetitive literatures were excluded.RESULTS AND CONCLUSION:The preparation methods of strontium-substituted hydroxyapatite include liquid-phase method (hydrothermal method,acid-base neutralization and sol-gel method) and solid-phase method (mechanochemical method).In addition,strontium-substituted hydroxyapatite coating can be produced by electrochemical deposition and micro-arc oxidation.The introduction of strontium significantly modifies the crystal size,crystallinity,solubility and mechanical properties,and improves the biocompatibility,pro-osteogenesis and osteoclast inhibition of hydroxyapatite,but the optimal proportion of strontium needs to be further explored.Furthermore,the immune-regulation and osteogenic properties under pathological conditions of strontium-substituted hydroxyapatite need to be further improved.
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Objective To perform the research on the domestic hospital marketing. Methods Through deep discussion,data analysis and marketing survey,we conducted a research on the market positioning and marketing strategies for Shanghai Ruijin-Harvard Heart Center which is a Sino-foreign joint venture. Results The demand is much bigger than the current supply in the market for cardiovascular diseases.The establishment of the center meets the demands of the market. Conclusion The center will focus on the adult patients in Shanghai and Yangtze Delta,and combine the external,internal and interactive marketing strategies.It may provide some useful experience for the Chinese hospital management,especially for hospital marketing.
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Object To prepare and study a suitable carrier for paclitaxel in water. Methods Cetyl chitosan (CTCS), prepared by reacting chitosan (CS) with chlorocetane under alkaline condition, was soluble and spontaneously formed nanosphere about 100 nm in diameter. And the release in vitro from paclitaxel loaded CTCS nanosphere was measured in phosphate buffer solution (PBS, pH=7 4). Results The balanced release concentration of paclitaxel was deceased and half release time (t 1/2 ) was delayed with the increase of substitution degree of alkyl. Conclusion This kind of nanosphere is an excellent carrier for paclitaxel in water.