Asthma ; etiology ; Bronchial Hyperreactivity ; etiology ; Humans ; Interleukin-16 ; genetics ; physiology ; Leukotriene C4 ; biosynthesis

Objective:To investigate the inhibitory effect of curcumin on oxidative stress in BCG-infected macrophages based on the Nrf2 pathway.Methods:THP-1-derived macrophages were infected.The experiment was divided into control group,BCG group,BCG+curcumin group and BCG+curcumin+ML385 group.Cellular ROS fluorescence intensity were observed under a fluores-cence microscope;Glutathione(GSH)levels were measured by Colorimetry;Western blot was used to detect the protein expressions of Nrf2,HO-1 and NQO1;MTT was used to detect the proliferation rate of macrophages.Results:BCG infection significantly enhanced ROS fluorescence intensity,reduced cell GSH content(P<0.01),inhibited protein expressions of Nrf2,HO-1 and NQO1,at the same time inhibited cell proliferation(P<0.01);curcumin significantly weakened ROS fluorescence intensity,increased GSH level(P<0.05),promoted Nrf2,HO-1 and NQO1 protein expressions and cell proliferation(P<0.01);Nrf2 inhibitor ML385 reversed the effect of curcumin.Conclusion:Curcumin can alleviate BCG-induced oxidative stress in macrophages by increasing the expression of Nrf2 and inducing the transcription of downstream antioxidant molecules.

Objective:To investigate the impairment mechanism of learning and memory ability induced by arsenite through studying the effects of arsenite on the expression level of CaMKⅡ in the hippocampus of offspring mice at different developmental stages. Methods:The model of offspring mice exposed to arsenite (0,15,30 and 60 mg/L NaAsO2) was set up. In postnatal day (PND) 10,20 and 40,the expression levels of CaMKⅡαand CaMKⅡβmRNA in the hippocampus were measured by real-time RT-PCR. Results:In PND 10 and PND 20, the expression levels of CaMKⅡ α and CaMKⅡ β mRNA in the hippocampus of offspring mice exposed to arsenite had no significant difference compared with those in control group. In PND 40, the expression levels of CaMKⅡα mRNA in the hippocampus of offspring mice exposed to arsenite were significantly lower than those in control group, the expression levels of CaMKⅡβ mRNA in the hippocampus of offspring mice exposed to 30 and 60 mg/L arsenite were significantly lower than those in control group (P<0.05) . Conclusion:Arsenite can affect the expression levels of CaMKⅡsubunits in the hippocampus of offspring mice and further may impair the learning and memory ability.

ObjectiveTo analyze the outcome of psychiatric prevention and therapy program in the community in Huicheng District,Huizhou city.MethodsThe variables of supervision rate,improvement rate,society participation rate,disturbance creating rate of violence,the mean recurrence frequency in one year and hospitalization rate,etc.were observed in psychiatric patients pre-and post initiation of the program as the model of socialization,complexity,accessibility.Results3 years after carrying out the program in Huicheng District of Huizhou city,the supervision rate,improvement rate,society participation rate of psychiatric patients have significantly increased,and the disturbance creating rate of violence,the mean recurrence frequency in one year and hospitalization rate have substantially decreased.ConclusionThe psychiatric prevention and therapy program in the community in Huicheng District,Huizhou city has been shown to be an effective way for psychiatric intervention.

OBJECTIVETo investigate the anti-cancer efficacy and mechanism of sorafenib and 5-fluorouracil (5-FU) therapy in vitro using the HCC cell line MHCCLM3.

METHODSThe effects of sorafenib and 5-FU, alone or in combination, on the proliferation of MHCCLM3 cells were evaluated by cell viability assays. Combined-effects analyses were conducted according to the median-effect principle established by Chou and Talalay. Effects on cell cycle distributions were tested by flow cytometry and expression of proteins related to the RAF/MEK/ERK and STAT3 signaling pathways and cyclinD1 were tested by western blotting.

RESULTSSorafenib and 5-FU alone or in combination displayed significant efficacy in inhibiting proliferation of the MHCCLM3 cells, with the following inhibition rates: sorafenib: 46.16% +/- 2.52%, 5-FU: 28.67% +/- 6.16%, and sorafenib + 5-FU: 22.59% +/- 6.89%. The sorafenib + 5-FU combination did not provide better results than treatment with either drug alone. The combination index values of the sorafenib and 5-FU treatments were mainly greater than 1, indicating that the two agents induced antagonistic, instead of synergistic, effects on the MHCCLM3 cells. In addition, the MHCCLM3 cells were less sensitive to 5-FU when administrated in combination with sorafenib, as evidenced by the half inhibitory concentration (IC50) significantly increasing from (102.86 +/- 27.84) mg/L to (178.61 +/- 20.73) mg/L (P = 0.003). Sorafenib alone induced G1 phase arrest (increasing from 44.73% +/- 1.63% to 65.80% +/- 0.56%; P less than 0.001) and significantly decreased the proportion of cells in S phase (decreasing from 46.63% +/- 0.65% to 22.83% +/- 1.75%; P less than 0.01), as well as down-regulated cyclinD1 expression (0.57 +/- 0.03-fold change vs. untreated control group; P less than 0.01). 5-FU alone up-regulated cyclinD1 expression (1.45 +/- 0.12-fold change vs. untreated control group; P less than 0.01). Moreover, sorafenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways, with the fold-changes of p-C-RAF, p-ERK1/2 and p-STAT3 being 0.56 +/- 0.05, 0.54 +/- 0.02 and 0.36 +/- 0.02, respectively (all P less than 0.01); 5-FU alone produced no significant effects on these pathways.

CONCLUSIONAdministered alone, both sorafenib and 5-FU exert anti-tumoral activity on in vitro cultured HCC cells. The sorafenib + 5-FU combination treatment produces antagonistic, rather than synergistic, effects. Sorafenib-inhibited RAF/MEK/ERK and STAT3 signaling and cyclinD1 expression may have induced the observed G1phase arrest and S phase reduction, thereby reducing the cells' sensitivity to 5-FU.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Drug Antagonism ; Fluorouracil ; pharmacology ; Humans ; Niacinamide ; analogs & derivatives ; pharmacology ; Phenylurea Compounds ; pharmacology ; STAT3 Transcription Factor ; metabolism ; Signal Transduction

OBJECTIVETo investigate the changes of pulmonary function and fractional exhaled nitric oxide (FeNO) in the standardized treatment of bronchial asthma in children.

METHODSA total of 254 children who were newly diagnosed with acute exacerbation of bronchial asthma were selected as asthma group, and they were divided into two subgroups: asthma with concurrent rhinitis and asthma without concurrent rhinitis. All patients received the standardized management and treatment for one year. The pulmonary function parameters included forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), and mid-expiratory flow at 25%, 50%, and 75% of vital capacity (MEF25, MEF50, and MEF75). The FeNO levels were measured before treatment and at 3, 6, 9, and 12 months after treatment. Another 62 healthy children were selected as the control group, and the pulmonary function and FeNO levels were measured only once.

RESULTSDuring one year of standardized treatment, FEV1, PEF, MMEF, MEF25, MEF50, and MEF75 gradually increased, and FeNO levels gradually decreased (P<0.05). Indicators of large airway function, such as FEV1 and PEF, almost returned to normal after 6 months of treatment; indicators of small airway function, such as MMEF, MEF25, MEF50, and MEF75 almost returned to normal after 9 months of treatment; there were no significant differences in the above indices between the asthma group and the control group after one year of treatment (P>0.05). However, the asthma group had a significantly higher FeNO levels than the control group after one year of treatment (P<0.05). The asthmatic patients with concurrent rhinitis had significantly higher FeNO levels than those without concurrent rhinitis before treatment and 3 months after treatment (P<0.05). Before treatment, there was a significant negative correlation between FeNO levels and pulmonary function parameters (P<0.05).

CONCLUSIONSWith the standardized treatment of bronchial asthma in children, pulmonary function parameters gradually increase and FeNO levels gradually decrease. The recovery of large airway function occurs earlier than the recovery of small airway function. Furthermore, the effect of rhinitis on airway responsiveness should be noted.

Asthma ; physiopathology ; therapy ; Breath Tests ; Child ; Female ; Forced Expiratory Volume ; Humans ; Lung ; physiopathology ; Male ; Maximal Midexpiratory Flow Rate ; Nitric Oxide ; analysis ; Rhinitis ; physiopathology

OBJECTIVETo compare the 2-DE profiles for serum proteins of different pathological stages during hepatocarcinogenesis.

METHODSSera from hepatocellular carcinoma patients, cirrhosis patients, chronic hepatitis patients and healthy controls were collected. After sonication, albumin and immunoglobulin (IgG) depletion, and desalination, sera were subjected to 2-DE, the differential protein spots were identified by MALDI-TOF-MS. Western blot was used to validate these differentially expressed proteins.

RESULTS2-DE sera protein profiles were obtained from the patient suffering from HCC, liver cirrhosis, chronic hepatitis, healthy controls in each group. From optimized 2-DE gel images of the above groups, 96 protein spots with more than 2-fold difference in intensity between the two groups were selected by image master 6.0 software, differential proteins including haptoglobin, SAA1 and SP40 were identified by MALDI-TOF-MS/MS. 7 different spots within more than 30 protein spots belonged to the same haptoglobin family. The differential expression of haptoglobin was confirmed by western blot.

CONCLUSIONSFour protein expression patterns have been identified during the pathological stages of hepatocarcinogenesis. Haptoglobin is significantly increased from liver cirrhosis to HCC. It implies that haptoglobin might be a potential biomarker in the early diagnosis of liver cancer.

Adult ; Biomarkers, Tumor ; blood ; Blood Proteins ; analysis ; Blotting, Western ; Electrophoresis, Gel, Two-Dimensional ; methods ; Female ; Haptoglobins ; analysis ; Hepatitis, Chronic ; blood ; pathology ; Humans ; Liver Cirrhosis ; blood ; pathology ; Liver Neoplasms ; blood ; pathology ; Male ; Middle Aged ; Proteome ; metabolism ; Proteomics ; methods ; Young Adult

Objective To investigate the metabolomics characteristic of neuromyelities optica spectrum disorder (NMOSD) in plasma and cerebrospinal fluid.Methods Ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify plasma metabolites in 16 patients with NMOSD and 8 healthy controls.At the same time,the identification of metabolites in cerebrospinal fluid of 8 NMOSD patients and 5 healthy controls was completed.Differential metabolites screening and metabolomic pathway analysis were performed by diversified data analysis methods.Results Compared with healthy control group,the content of 8 substances such as Cis.8.11.14.Eicosatrienoic acid in the plasma of NMOSD patients was increased.The content of 8 substances such as L-glutamine acid were decreased.There was no significant difference in the metabolites between Aquaporin 4 (AQP-4) antibody positive and negative NMOSD plasma.The content of 6 substances such as 3-hydroxybutyric acid in cerebrospinal fluid of patients with NMOSD was reduced.Conclusions The distribution of metabolites in plasma between NMOSD patients and healthy controls was significantly different.There was no significant difference in metabolites between AQP-4 antibody positive and negative NMOSD plasma.There are some differences in metabolites between cerebrospinal fluid of NMOSD patients and healthy controls.A variety of amino acid abnormalities,sphingomyelin dysfunction,energy metabolism and mitochondrial dysfunction were involved in the pathogenesis of NMOSD.

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.