Fraxinellone, the major component of Cortex Dictamni, is naturally degraded limonids compound. Fraxinellone has significant anti-inflammatory activity in acute liver injury model. However, the low solubility and permeability of fraxinellone limited its potential application and even therapeutic effects. The aim of the paper is to increase oral bioavailability of fraxinellone, thus improving its hepatoprotection effect in vivo. We evaluated the effects of different pH values and different solubilizer (PEG 6000, PVP K30, HP-beta-CD, F68 and SDS) on the solubility of fraxinellone. The results showed that HP-beta-CD increased solubility of fraxinellone up to 155 times compared to that of water. More than 2. 1 mg mL1 fraxinellone can be resolved when adding 20% HP-beta-CD. Mouse acute liver injury model induced hy CCl4 was used to evaluate in vivo activity of fraxinellone with or without HP-beta-CD. The result shows that the hepatoprotective activity of fraxinellone in 20% HP-beta-CD solution has been significantly improved compared with that of fraxinellone solution without HP-beta-CD: the former inhibited 59 percent the increase of enzyme activity of ALT in liver, while the latter only inhibited 20 percent. A LC-MS/MS method was also developed to determine the oral bioavailability of fraxinellone. Fraxinellone solution with or without HP-betaCD were administered intra-gastrically to rats, and it was found that the bioavailahility of fraxinellone with HP-beta-CD was 23%, while only 5% without HP-beta-CD. The result showed that HP-beta-CD can significantly increase the solubility and permeability of fraxinellone, and improve bioavailability 3. 5 fold in vivo acute liver injury model as well as administration.
Animals ; Benzofurans ; chemistry ; pharmacokinetics ; pharmacology ; Biological Availability ; Carbon Tetrachloride ; toxicity ; Female ; Hydrogen-Ion Concentration ; Liver ; drug effects ; Male ; Mice ; Mice, Inbred ICR ; Rats ; Rats, Sprague-Dawley ; Solubility

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
Adenocarcinoma ; genetics ; metabolism ; Apoptosis ; genetics ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; DNA Methylation ; Exons ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Insulin-Like Growth Factor Binding Proteins ; genetics ; metabolism ; Transfection ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo investigate the clinical therapeutic effect of methylprednisolone combined with cyclophosphamide and Etanercept method on acute paraquat poisoning.

METHODS136 patients with acute paraquat poisoning were divided into the normal therapy group and the intensive therapy group randomly. Methylprednisolone, cyclophosphamide and Etanercept were used in the intensive therapy group. Methylprednisolone 500 mg was given intravenously per day for continuous three days followed by 200 mg intravenous per day. Then methylprednisolone was decreased gradually 14 d or 21 d later according to the patient's condition. Cyclophosphamide 600 mg was given intravenously twice weekly for 2 weeks and Etanercept 25 mg was given hypodermic injection twice weekly for 3 weeks. Curative effect evaluation was done at 7, 14, 21 d and 12 weeks after therapy.

RESULTSThe survival rate of the intensive therapy group was obviously higher than that of the normal therapy group (P<0.01) on 7, 4, 21 d and 12 weeks. The cure rate of the intensive group were 94.6% (intake dose<50 ml 20% paraquat solution), 75.0% (intake dose 50 approximately 100 ml 20% paraquat solution), 12.5% (intake dose>100 ml 20% paraquat solution) respectively, while the cure rate of the normal group were 16.7% (intake dose<50 ml 20% paraquat solution), 8.3% (intake dose 50 approximately 100 ml 20% paraquat solution), 0% (intake dose>100 ml 20% paraquat solution) respectively. The total cure rate of the intensive therapy group (78.3%) 12 weeks later was higher than that of the normal group (11.9%).

CONCLUSIONMethylprednisolone combined with cyclophosphamide and Etanercept intensive therapy has the curative effect on acute paraquat poisoning.

Acute Disease ; Adolescent ; Adult ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Etanercept ; Female ; Humans ; Immunoglobulin G ; administration & dosage ; therapeutic use ; Male ; Methylprednisolone ; administration & dosage ; therapeutic use ; Middle Aged ; Paraquat ; poisoning ; Poisoning ; drug therapy ; Receptors, Tumor Necrosis Factor ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult

Objective To fulfill standardized and precision management of medical consumables purchasing. Methods Medical consumables purchasing was executed based on the e-commerce platform in the drug exchange facility, the access process was standardized for medical consumables, and the monitoring and supervision were implemented for price inquiry, purchasing ways, introduction flow of new products, qualification inspecting of suppliers and etc. Results The improved medical consumables purchasing flow based on drug exchange mode contributed to decreasing purchasing cost, avoiding bidding risks as well as precision management. Conclusion The purchasing based on drug exchange is of great value for hospital medical consumables purchasing management.

ObjectiveTo explore the predictive role of the degree of prospective memory impairment on the treatment response to Selective Serotonin Reuptake Inhibitors （SSRIs） in patients with obsessive-compulsive disorder. MethodsA total of 30 patients with obsessive-compulsive disorder who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fourth edition， text revision （DSM-IV-TR） were selected， and all patients were treated with SSRIs for 4 weeks. The severity of obsessive-compulsive symptom was assessed using Yale-Brown Obsessive Compulsive Scale （Y-BOCS）， and the efficacy was evaluated by the reduction rate of Y-BOCS score. Moreover， the performance of event-based， time-based and activity-based prospective memory tasks were compared before and after treatment. ResultsAfter treatment， the total Y-BOCS score of patients was lower than before treatment ［（27.07±4.63） vs. （24.87±5.93）， F（1，29）=4.984， P=0.033］， meantime， the performance of event- and time- based prospective memory tasks was improved ［（0.78±0.21） vs. （0.88±0.11）， F（1，29）=9.022， P=0.005； （0.81±0.17） vs. （0.91±0.11）， F（1，29）=9.063， P=0.005］. Correlation analysis showed that the performance of event-based prospective memory at baseline was positively correlated with the reduction of Y-BOCS score （r=0.478， P=0.014）. The event-based prospective memory performance at baseline could positively predict the treatment response to SSRIs treatment in patients （β=0.441， P=0.014）. ConclusionThe event-based prospective memory function of patients with obsessive-compulsive disorder can positively predict SSRIs treatment outcome， and patients with better prospective memory performance yield better treatment responses.

ObjectiveTo study the prospective memory deficits of obsessive-compulsive disorder patients and unaffected first-degree relatives of patients， so as to validate the possibility of prospective memory as an endophenotype of obsessive-compulsive disorder. MethodsHealthy controls， obsessive-compulsive disorder patients and unaffected first-degree relatives of patients， each with 25 cases， matched for age， education， gender， IQ and marriage status were enrolled. The standardized prospective memory paradigm with a multi-trial design was conducted， and the accuracy was used as an indicator of prospective memory function. ResultsThe accuracy of event- and time-based prospective memory tasks of obsessive-compulsive disorder patients was lower than that of healthy controls， with statistical differences ［（0.74±0.24） vs. （0.88±0.13）， d=-0.140， P=0.044； （0.77±0.21） vs. （0.93±0.10）， d=-0.164， P=0.011］. The accuracy of event-based prospective memory task of unaffected first-degree relatives was also lower than that of healthy controls， with statistical difference ［（0.73±0.20） vs. （0.88±0.13）， d=-0.144， P=0.036］. ConclusionObsessive-compulsive disorder patients has extensive prospective memory deficits， indicating that prospective memory may be an endophenotype of obsessive-compulsive disorder.