Thrombin Induces Secretion of Multiple Cytokines and Expression of Protease-Activated Receptors in Mouse Mast Cell Line.

BACKGROUND: Thrombin could elicit degranulation of mast cells involved in numerous physiologic and pathologic processes; however, the detailed scrutiny of this procedure and further research of possible cell signaling pathways are lacking. METHODS: P815 mouse mast cells were exposed to various concentrations of thrombin for 16 h. Expression of protease-activated receptor (PAR)1, PAR2, PAR3, and PAR4 mRNA in P815 was analyzed by quantitative real-time PCR (qRT-PCR) and the fittest concentration of thrombin was decided. Then, secretions of mediators from P815 stimulated by thrombin 0.2 U/ml were determined using enzyme-linked immunosorbent assay (ELISA) and Luminex liquichip; the possible cell signaling pathways were measured by immunoblotting. Furthermore, inhibition of thrombin inhibitor (hirudin), PAR1 inhibitor (SCH79797), and MAPK inhibitors (SB203580, PD98059, and SP600125) on the mediator section was evaluated by ELISA and Luminex liquichip. RESULTS: Thrombin 0.2 U/ml induced the elevated expression of PAR1, PAR2, PAR3, and PAR4, as well as the increasing level of phospho-IκBα, phospho-SAPK/JNK MAPK, phospho-P38 MAPK (Thr180/Tyr182), and phospho-ERK1/2 MAPK (p44/42) in P815. Secretion of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin- (IL-) 2, IL-6, chemokine ligand- (CCL-) 2, chemokine (C-X-C motif) ligand- (CXCL-) 1, and CXCL-5 from P815 increased apparently; this effect could be diminished by hirudin, whereas SCH79797 and MAPK inhibitors (SB203580, PD98059, and SP600125) diminish the secretions with weaker effect. CONCLUSION: We found the expression of PAR mRNA in P815, activation of signaling pathways of nuclear factor-kappaB (NF-κB), and mitogen-activated protein kinases (MAPKs) including C-Jun NH2-terminal kinase (JNK), P38, and extracellular signal-regulated kinase 1/2 (ERK1/2), and the release of multiple inflammatory mediators stimulated by thrombin, as well as the inhibition of the inflammatory releases by hirudin, SCH79797, and MAPK inhibitors including SB203580, PD98059, and SP600125.

Manufacture of low-fat Cheddar cheese by exopolysaccharide-producing Lactobacillus plantarum JLK0142 and its functional properties.

This study aimed to evaluate the effect of exopolysaccharide (EPS)-producing Lactobacillus plantarum JLK0142 on the ripening characteristics and in vitro health-promoting benefits of low-fat Cheddar cheese. Three batches of cheese were made by employing a non-EPS-producing cheese starter (control), in combination with Lb. plantarum JLK0142 as an adjunct and the purified EPS as an ingredient. Lactobacillus plantarum JLK0142 survived well in cheese, with counts of 7.99 log cfu/g after 90 d of ripening. All experimental cheeses (with adjunct culture or EPS ingredient) had higher moisture, proteolysis, and sensory scores, and lower hardness and cohesiveness compared with the control cheese. Water-soluble extracts from the experimental cheeses outperformed that of the control in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and hydroxyl radicals, and inhibiting α-amylase, angiotensin-converting enzyme, and HT-29 tumor cell growth. Therefore, incorporation of the EPS-producing culture of Lb. plantarum JLK0142 is promising for improvement of low-fat cheese quality and bioactivities.

Pluronic F68-Linoleic Acid Nano-spheres Mediated Delivery of Gambogic Acid for Cancer Therapy.

Gambogic acid (GA), a natural compound from gamboge resin, has been introduced as a promising antitumor drug contributing to its broad spectrum of antitumor activity. However, the poor aqueous solubility and short half-life hinder its clinical application. Pluronic F68 (F68) is a well-known amphiphilic block copolymer consisting of hydrophobic propylene oxide units and hydrophilic ethylene oxide. Although F68 has an amphiphilic structure, its short propylene oxide segment limits its dilution stability and drug-loading capacity. To overcome this limitation, we modified F68 by conjugating linoleic acid, a hydrophobic fatty acid, to increase the hydrophilic-hydrophobic interaction and thus improve the stability of F68 nano-spheres. This F68-linoleic acid (F68-LA) conjugate was synthesized and was used to load GA to improve its anticancer effects. GA-loaded F68-LA nano-spheres were stable for 6 days, with a mean diameter of 159.3 nm and zeta potential of -23.2 mV. The entrapment efficiency of GA in F68-LA nano-spheres was as high as 92.0%. Furthermore, F68-LA/GA nano-spheres exhibited an enhanced cytotoxic activity and proapoptotic effect against human ovarian cancer A2780 cells, compared with free GA. Our results showed that the F68-LA/GA nano-spheres might be a promising cancer-targeted drug delivery system in ovarian cancer therapy.

Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy.

Glycyrrhetinic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the root of licorice, has been used in hepatocellular carcinoma (HCC) therapy. Particularly, GA as a ligand in HCC therapy has been widely explored in different drug delivery systems, including liposomes, micelles, and nanoparticles. There is considerable interest worldwide with respect to the development of GA-modified drug delivery systems due to the extensive presence of GA receptors on the surface of hepatocyte. Up until now, much work has been focused on developing GA-modified drug delivery systems which bear good liver- or hepatocyte-targeted efficiency both in vitro and in vivo. Owing to its contribution in overcoming the limitations of low lipophilicity and poor bioavailability as well as its ability to promote receptor-mediated endocytosis, GA-modified drug delivery systems play an important role in enhancing liver-targeting efficacy and thus are focused on the treatment of HCC. Moreover, since GA-modified delivery systems present more favorable pharmacokinetic properties and hepatocyte-targeting effects, they may be a promising formulation for GA in the treatment of HCC. In this review, we will give an overview of GA-modified novel drug delivery systems, paying attention to their efficacy in treating HCC and discussing their mechanism and the treatment effects.

A Redox-Sensitive and RAGE-Targeting Nanocarrier for Hepatocellular Carcinoma Therapy.

Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells. Specifically, we modified Pluronic F68 (F68) with APDTKTQ (F68-APDTKTQ), and we conjugated d-α-tocopheryl polyethylene glycol succinate (TPGS) with poly(lactic-co-glycolic acid) (PLGA) by a disulfide linker (TPGS-S-S-PLGA). We mixed TPGS-S-S-PLGA and F68-APDTKTQ (TSP/FP) to form a micelle, followed by the loading of oridonin (ORI). The prepared micelles showed a homogeneously spherical shape without aggregation, triggered an increased cellular uptake, and induced apoptosis in more cells than did the free ORI. Taken together, these results demonstrate the potential of this APDTKTQ-modified ORI-loaded TSP/FP mixed micelle system as a promising strategy for HCC-targeting therapy.

[Comparative a nimble of monitoring indicator, explore the superiority about Supreme dual-chamber laryngeal mask used for cesarean section anesthesia].

OBJECTIVE: Explore the feasibility and superiority about Supreme double-lumen laryngeal mask airway for cesarean section anesthesia. METHODS: From March 2011 to March 2012, a total of 300 patients with American Society of Anesthesiologists (ASA) I or II foot of cesarean section in full-term pregnant women for the first time production of Quanzhou Women's and Children's Hospital were recruited, authenticated by Hospital Ethics Committee, they were randomly divided into three groups (Random number table), dual-chamber in the LMA group (A group of 100 cases), tracheal intubation group (B group of 100 cases) and spinal anesthesia group (C group of 100 cases). ECG, SpO2, MAP, heart rate, Narcotrend and Apgar scores were observed. RESULTS: Before and after the LMA group inserted laryngeal mask HR,MAP no significant change in the performance of Narcotrend value remained at the level of anesthesia, intubation before and after HR, MAP significantly increased performance of Narcotrend values significantly increased, both compared to the obvious statistical difference (P < 0.05). The ventilation indicators of two groups compared to no significant difference (P > 0.05). LMA group cover required intubation time was significantly shorter than the time required for intubation of endotracheal intubation group (P < 0.01). Three groups of patient administration to the fetus at all times is in 5-10 min.Three groups similar to the Apgar score was no significant difference (P > 0.05). CONCLUSION: The dual-chamber laryngeal mask airway for caesarean section anesthesia, fetal Apgar scores, feasibility, and its operation is easy, safe and comfortable anesthesia, compared tracheal intubation has obvious superiority.

Involvement of CCL2 and CH25H Genes and TNF signaling pathways in mast cell activation and pathogenesis of chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU), a mast cell-driven disease, substantially affects the quality of life. While genetics affect CSU susceptibility and severity, the specific genetic factors associated with mast cell activation in CSU remain elusive. We aimed to identify key genetic factors and investigate their roles in CSU pathogenesis. Two gene expression datasets from the Gene Expression Omnibus were merged and validated using principal component analysis and boxplots. The merged dataset was subjected to limma and weighted gene co-expression network analyses. Genes whose expression correlated highly with CSU were identified and analyzed using Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. As GSEA, GO, and KEGG analyses highlighted the importance of chemokine (C-C motif) ligand 2 (CCL2) and cholesterol 25-hydroxylase (CH25H) gene and tumor necrosis factor (TNF) signaling pathways in CSU; the three corresponding genes were knocked down in human mast cell line-1 (HMC-1), followed by incubation with thrombin to mimic CSU pathogenesis. CCL2, CH25H, and TNF knockdown reduced excitability and cytokine production in HMC-1. Our findings suggest that genes involved in the CCL2, CH25H, and TNF pathways play crucial roles in CSU pathogenesis, providing insights into potential therapeutic targets for CSU treatment.

The role of cGAS-STING signaling in pulmonary fibrosis and its therapeutic potential.

Pulmonary fibrosis is a progressive and ultimately fatal lung disease, exhibiting the excessive production of extracellular matrix and aberrant activation of fibroblast. While Pirfenidone and Nintedanib are FDA-approved drugs that can slow down the progression of pulmonary fibrosis, they are unable to reverse the disease. Therefore, there is an urgent demand to develop more efficient therapeutic approaches for pulmonary fibrosis. The intracellular DNA sensor called cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) plays a crucial role in detecting DNA and generating cGAMP, a second messenger. Subsequently, cGAMP triggers the activation of stimulator of interferon genes (STING), initiating a signaling cascade that leads to the stimulation of type I interferons and other signaling molecules involved in immune responses. Recent studies have highlighted the involvement of aberrant activation of cGAS-STING contributes to fibrotic lung diseases. This review aims to provide a comprehensive summary of the current knowledge regarding the role of cGAS-STING pathway in pulmonary fibrosis. Moreover, we discuss the potential therapeutic implications of targeting the cGAS-STING pathway, including the utilization of inhibitors of cGAS and STING.

A new potential NLO compound with a supramolecular layered structure: aqua(hexamethylenetetramine-κN)(iminodiacetato-κ3O,N,O')copper(II).

In the noncentrosymmetric title compound, [Cu(C(4)H(5)NO(4))(C(6)H(12)N(4))(H(2)O)] or [Cu(IDA)(HMTA)(H(2)O)], where IDA is iminodiacetate and HMTA is hexamethylenetetramine, the asymmetric unit consists of a whole mononuclear neutral molecule, where the Cu(II) cation is coordinated by two carboxylate O atoms and one N atom from the IDA ligand, by one N atom from the HMTA ligand and by the O atom of the coordinated water molecule, giving rise to a CuN(2)O(3) distorted square-pyramidal coordination geometry. The IDA and HTMA ligands adopt terminal tri- and monocoordinated modes, respectively. All adjacent molecules within the ac plane are connected to each other via two pairs of O-H···O and one N-H...O hydrogen bond, forming a (4,4) supramolecular two-dimensional network. In the unit cell, these layers stack alternately in an …ABABAB… sequence along the b axis. The optical absorption properties of this compound have been studied on powder samples, which had previously been examined by powder X-ray diffraction.

Plasma-Derived Exosomes in Chronic Spontaneous Urticaria Induce the Production of Mediators by Human Mast Cells.

Mast cell activation and inflammatory mediators play central roles in the pathogenesis of chronic spontaneous urticaria (CSU). The factors that induce mast cell activation in CSU are still largely unknown. Exosomes (EXs) are extracellular vesicles that activate mast cells. In this study, we enriched the EXs derived from the plasma of healthy volunteers and that of patients with CSU without antihistamine sensitivity (i.e., CSU-derived EXs with antihistamine sensitivity) or resistance (i.e., CSU-derived EXs with antihistamine resistance) using ultracentrifugation. We then incubated these EXs with HMC-1 human mast cells. Notably, CSU-derived EXs with antihistamine sensitivity and CSU-derived EXs with antihistamine resistance increased tryptase-1 expression; histamine production; inflammatory mediator production; and toll-like receptor (TLR) 2, TLR4, and phosphorylated MAPK levels in HMC-1 cells. These effects were more significant in the group with CSU-derived EXs with antihistamine resistance than in the group with CSU-derived EXs with antihistamine sensitivity. TLR2, TLR4, and MAPK inhibitors (CC-401, TAK-715, and SCH772984, respectively) reduced CSU-derived EXs-Stimulated production of inflammatory mediators in HMC-1 cells. Overall, EXs in the plasma of patients with CSU were found to activate mast cells and elicit the production of multiple inflammatory mediators, partly through the TLR2, TLR4, and MAPK pathways. In addition, CSU-derived EXs with antihistamine resistance had more powerful mast cell‒activating and histamine-release abilities. Thus, these EXs may be involved in the pathogenesis of CSU with antihistamine resistance.

Thrombin induces pro-inflammatory and anti-inflammatory cytokines secretion from human mast cell line (HMC-1) via protease-activated receptors.

Thrombin-induced mast cell activation represents cross-talk between coagulation and inflammation. However, there is still controversy concerning the pro- or anti-inflammatory effects mast cells have in response to thrombin signaling. Human mast cell HMC-1 was incubated with 0.2 U/mL thrombin. Cells and supernatants were collected. Production of pro- and anti-inflammatory mediators was determined by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). Expression of proteinase-activated receptor-1 (PAR1) and -4 (PAR4) mRNA in HMC-1 cells was analyzed by qPCR. Activation of mitogen-activated protein kinases (MAPKs) was measured by immunoblotting. Furthermore, the impact of PAR1 inhibitor (SCH79797) and agonist (TFLLR-NH2), PAR4 inhibitor (BMS986120) and agonist (AYPGKF-NH2), and MAPK inhibitors (SB203580, PD98059, and SP600125) on the production of mediators was evaluated using qPCR and ELISA. Thrombin exposure increased pro- and anti-inflammatory mediators, expression of PAR1 and PAR4 mRNA, and phosphorylation of JNK, p38, and ERK1/2 MAPKs in HMC-1 cells. SCH79797, BMS986120, and MAPK inhibitors (SB203580, PD98059, and SP600125) were inhibited, while TFLLR-NH2 and AYPGKF-NH2 promoted pro- and anti-inflammatory cytokines in this process. HMC-1 produces pro- and anti-inflammatory cytokines after thrombin incubation, namely PAR1 and PAR4. Alongside HMC-1, MAPK signaling pathways are involved in the production of these mediators. The mast cells showed dual activation after thrombin stimulation.

Exosomes From Packed Red Cells Induce Human Mast Cell Activation and the Production of Multiple Inflammatory Mediators.

Most blood transfusion-related adverse reactions involve the immunologic responses of recipients to exogenous blood components. Extracellular vesicles isolated from packed red cells can affect the recipient's immune system. Mast cells are traditionally known as effector cells for allergic transfusion reactions. However, growing evidence supports the notion that activated mast cells might disturb host innate immunologic responses. Exosomes are a type of extracellular vesicle. To determine the effect of exosomes on mast cells, we enriched exosomes derived from volunteer plasma (EXs-nor) and packed red cells (EXs-RBCs) using ultracentrifugation and incubated them with a human mast cell line (HMC-1). We found that EXs-RBC exposure increased the expression of tryptase-1 and prostaglandin D2, the production of multiple inflammatory mediators, and the levels of Toll-like receptor-3 (TLR-3) and phospho-mitogen-activated protein kinase (MAPK) in HMC-1 cells. MAPK inhibitors (SB203580, PD98059, and SP600125) and a TLR-3/dsRNA complex inhibitor reduced the EXs-RBC-stimulated production of inflammatory mediators in HMC-1 cells, whereas the TLR-3 agonist [poly (A:U)] elevated the production of these mediators. These results indicate that EXs-RBCs activate HMC-1 cells and elicit the production of multiple inflammatory mediators, partly via the TLR-3 and MAPK pathways. Mast cells activated by EXs-RBCs exhibit complex inflammatory properties and might play a potential role in transfusion-related adverse reactions.

In vitro immunomodulatory effects of acidic exopolysaccharide produced by Lactobacillus planetarium JLAU103 on RAW264.7 macrophages.

Previous work from our research group has isolated and purified an acidic exopolysaccharide (named EPS103) from Lactobacillus plantarum JLAU103, which had strong in vitro antioxidant activity. In this study, we investigated the in vitro immunomodulatory activity of EPS103 in RAW264.7 macrophages with or without lipopolysaccharide (LPS) activation. The results showed that EPS103 enhanced the phagocytic activity of RAW264.7 macrophages and promoted the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) of RAW264.7 macrophages. Moreover, EPS103 reduced the excessive release of IL-6, TNF-α, prostaglandin E2 (PGE2), and NO, as well as inhibited the mRNA expression of IL-6, TNF-α, cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) of RAW264.7 macrophages activated by LPS. In mechanistic studies, EPS103 exerted immunomodulatory activity via the nuclear factor-kappa B (NF-κB) signaling pathway. These findings suggest that EPS103 possesses potent dual immunomodulatory activities and could be further developed as new products for functional foods or medicines.

Characterization and antioxidant activity of an acidic exopolysaccharide from Lactobacillus plantarum JLAU103.

An acidic exopolysaccharide (EPS) designated as EPS103 was isolated, purified and characterized from Lactobacillus plantarum JLAU103. EPS103 had a relatively lower molecular weight of 12.4 KDa and was consisted of arabinose, rhamnose, fucose, xylose, mannose, fructose, galactose, and glucose in an approximate molar ratio of 4.05: 6.04: 6.29: 5.22: 1.47: 5.21: 2.24: 1.83. A specific spectrogram of acidic polysaccharide was obtained by FT-IR analysis, and both α- and ß-type configurations were presented in EPS103 based on the nuclear magnetic resonance spectroscopy. Microstructural analysis of EPS103 demonstrated a smooth and glittering cube structure, and presence of many homogeneous rod-shaped lumps. Comprehensive study of in vitro antioxidant activity indicated that EPS103 possess strong scavenging abilities against hydroxyl, ABTS, and DPPH radicals with the maximum of 80.4%, 65.5%, and 60.5%, respectively, at 10 mg/mL concentration. Furthermore, EPS103 also showed strong ferrous ions chelating activity and oxygen radical absorbance capacity. These results together indicated that the EPS103 isolated from L. plantarum JLAU103 has great potential for use as a natural antioxidant or functional additive in foods industry.

Characterization and immunomodulatory activity of an exopolysaccharide produced by Lactobacillus plantarum JLK0142 isolated from fermented dairy tofu.

A purified neutral exopolysaccharide (EPS) designated as EPS0142 was obtained from Lactobacillus plantarum JLK0142. EPS0142 consisted of glucose and galactose in an approximate molar ratio of 2.13:1.06 and had a molecular weight of 1.34 × 105 Da. The FT-IR spectrum showed that EPS0142 had a typical polysaccharide absorption pattern. 1H NMR and 13C NMR spectra analysis showed the presence of N-acetylated sugar residues. EPS0142 had no toxic effects on RAW 264.7 cells and significantly improved their phagocytic activity and NO secretion in vitro. Further in vivo studies revealed that the spleen index and splenic lymphocyte proliferation activities of the cyclophosphamide-induced immunosuppression mice treated with a middle-dose (50 mg/kg body weight) or a high-dose (100 mg/kg body weight) of EPS0142 were significantly increased (P < 0.01). In addition, the intestinal immunoglobulin A (sIgA) content and the serum levels of the cytokines, IL-2 and TNF-α, were also significantly (P < 0.05) improved in the high-dose EPS0142 group compared to that in the model control group. These data indicate that the EPS isolated from L. plantarum JLK0142 can effectively improve the immunomodulatory activity of RAW 264.7 cells and stimulate the immune system in cyclophosphamide-induced immunosuppressed mice.

Redox-sensitive micelles composed of disulfide-linked Pluronic-linoleic acid for enhanced anticancer efficiency of brusatol.

Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway.

General Anesthesia with the Use of SUPREME Laryngeal Mask Airway for Emergency Cesarean delivery: A Retrospective Analysis of 1039 Parturients.

In comparison to elective cesarean delivery, emergency cesarean delivery under endotracheal intubation is associated with higher risk of life-threatening airway problems. In this retrospective study, we evaluate the efficacy and feasibility of using SUPREME laryngeal mask airway (SLMA) in emergency cesarean delivery under general anesthesia (GA). The study included a total of 1039 paturients undergoing emergency cesarean delivery under GA with SLMA from January 2015 to December 2015 at Quanzhou Children's and Women's Hospital. Outcome measures included incidence of the adverse events related to using SLMA, maternal mortality, and neonatal outcomes. Briefly, no aspiration or regurgitation was noticed; the first attempt was successful in all but 2 subjects, both because of incorrect location, one was detected by decreasing oxygenation and the other by high airway pressure, the second attempt was successful in both cases. No subject was switched to endotracheal intubation. No laryngospasm or bronchospasm was detected. No maternal death occurred. There were 1139 neonates (including 944 single birth, 92 twins, 3 triplets) in this study, 5-min Apgar score was 7-10 in 1092 (96.72%) neonates. Thirty-seven (3.28%) neonates received endotracheal intubation. In conclusion, this retrospective study showed that the SLMA was used successfully in 1039 patients undergoing emergent cesarean delivery without any major complications. Vigilant attention by attending anesthesiologists is warranted.

[Design and application of bundle treatment plan in the early stage for severe human infection by avian influenza H7N9].

OBJECTIVE: To design bundle treatment plan in the early stage for severe human infection by avian influenza H7N9, and explore its clinical efficacy and application value. METHODS: Fifteen patients with severe human infection by avian influenza H7N9 in Guizhou Province from December 29th, 2016 to June 7th, 2017 were enrolled. Patients admitted from March 6th, 2017 to June 7th, 2017 served as a prospective observation period (bundle treatment group), and those from December 29th, 2016 to March 5th, 2017 were selected as a historical control period (conventional treatment group). Conventional treatment group was given conventional treatment such as isolation, anti-virus, symptomatic treatment, and traditional Chinese medicine and so on. Bundle treatment group was given bundle treatment on the basis of conventional treatment, including isolation, anti-virus, respiratory support, restrictive fluid management, immunotherapy, inhibition of inflammation, antibiotic therapy, nutritional support, prevention of hospital acquired infection (HAP), individual sedation, continuous blood purification (CBP) for acute kidney injury (AKI) and severe acute respiratory distress syndrome (ARDS) patients, and intensive care. A cluster of bundle treatment team was set up to ensure that all measures carried out smoothly. The gender, age, onset to diagnosis time, acute physiology and chronic health evaluation II (APACHE II) score, oxygenation index (PaO2/FiO2) at admission, the length of intensive care unit (ICU) stay, total hospitalization time and prognosis of the two groups were observed. Correlation analysis between bundle therapy and prognosis was analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was drawn, and the clinical value of bundle treatment was analyzed. RESULTS: There was no significant difference in gender, age, onset to diagnosis time, APACHE II score, PaO2/FiO2, the length of ICU stay, or total hospitalization time between bundle treatment group (n = 9) and conventional treatment group (n = 6), but the death patients in the bundle treatment group was significantly fewer than those in conventional treatment group (cases: 2 vs. 5, χ2 = 3.225, P = 0.041). Correlation analysis showed that there was a significant correlation between the mortality and whether received bundle treatment or not in patients who infected by avian influenza H7N9 (r = -0.875, P = 0.018). ROC curve analysis showed that the area under the ROC curve (AUC) of non-bundle treatment for predicting the death in patients with severe human infection by avian influenza H7N9 was 0.938, 95% confidence interval (95%CI) was 0.795-1.000, the sensitivity was 88.88%, and the specificity was 98.62%. CONCLUSIONS: Early bundle therapy has a significant effect on severe human infection by avian influenza H7N9, which can improve the prognosis and reduce the mortality of patients. It is worthy for clinical application.

Ultrasonic extraction, antioxidant and anticancer activities of novel polysaccharides from Chuanxiong rhizome.

Ultrasonic-assisted extraction technology was employed to prepare Ligusticum chuanxiong Hort polysaccharide. Single factor test and orthogonal experimental design were used to optimize the extraction conditions. The results showed that the optimal extraction conditions consisted of ultrasonic temperature of 80°C, ultrasonic time of 40 min and water to raw material ratio of 30 mL/g. Three novel polysaccharides fractions, LCX0, LCX1 and LCX2, were isolated and purified from the crude polysaccharides using DEAE-52 cellulose and Sephadex G-100 column chromatography. The molecular weight and monosaccharide composition of three LCX polysaccharides fractions were analyzed with gel permeation chromatography (GPC) and HPLC analysis, respectively. Furthermore, the antioxidant and in vitro anticancer activities of the polysaccharides were investigated. Compared with LCX0, LCX2 and LCX1 showed relative higher antioxidant activity and inhibitory activity to the growth of HepG2, SMMC7721, A549 and HCT-116 cells. It is suggested that the novel polysaccharides from rhizome of L. chuanxiong could be promising bioactive macromolecules for biomedical use.

Synthesis, characterization and anti-cancer activity of Pluronic F68-curcumin conjugate micelles.

Curcumin (CUR), a nontoxic polyphenol derived from the rhizome of turmeric (Curcuma longa), has been recognized as an anti-cancer and chemo-preventative agent. However, its clinical application for cancer treatment has been greatly limited due to its poor water-solubility and low bioavailability. To tackle this problem, Pluronic F68-CUR (F68-CUR) conjugate micelles, which are amphiphilic copolymers, were designed and synthesized in this study. These highly stable micelles with CUR concentrated in the core were formulated using the solvent evaporation method and were confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Physicochemical characterization of F68-CUR conjugate micelles revealed that high drug loading content (DL%; 0.248 mg CUR/1 mg F68) was achieved, and the average particle size of micelles was 115.2 ± 3.0 nm. Compared with free CUR, a significantly higher cytotoxicity against human breast cancer cell line MDA-MB-231 was observed in F68-CUR conjugate micelles. The IC50 value of F68-CUR conjugate micelles was 1.95-fold lower than that of free CUR, indicating that the anti-cancer activity of CUR was significantly improved in the micelles. Furthermore, apoptotic studies demonstrated that F68-CUR conjugate micelles induced more cell apoptosis than that of free CUR. Taken together, these results demonstrate that F68-CUR conjugate micelles are promising to improve the clinical effectiveness of CUR in cancer treatment.