Objective: To investigate the function and mechanism of phospholipase Cγ1 (PLCγ1) in cell-matrix adhesion in colorectal cancer. Methods: Highly metastatic colorectal cancer cell line LoVo and lowly metastatic colorectal cancer cell line SW480 were subjected to cell-matrix adhesion assay. U73122 (a specific inhibitor of PLC) and pyrrolidine dithiocarbamate (PDTC) (an inhibitor of NF-κB) were used to study the effect of PLCγ1 and NF-κB on cell-matrix adhesion. Furthermore, Western blot and gel electrophoresis mobility shift assay (EMSA) were performed to detect the mechanism of PLCγ1 in colorectal cancer cell adhesion to matrix. Results: Inhibition of PLCγ1 or NF-κB resulted in reduction of cell-matrix adhesion in a dose-dependent manner in LoVo cells(P<0.05), but had no marked effect on SW480 cells. Western blot analysis showed that epidermal growth factor (EGF) stimulated the phosphorylation of PLCγ1 in LoVo. The results of EMSA indicated that inhibition of PLCγ1 signaling pathway also down-regulated the activity of NF-κB while EGF reversed the function. Conclusion:These data suggest that PLCγ1 plays a pivotal role in the EGF-induced cell-matrix adhesion of highly metastatic colorectal cancer cells and that NF-κB is also functional in this signaling pathway.

ObjectiveTo investigate the clinical characteristics and pathogenic microorganisms in culture-positive sepsis, to identify its risk factors, and evaluate the prognosis on polymicrobial infection in intensive care unit (ICU).Methods A descriptive retrospective study was conducted. Clinical data of patients aged≥ 18 years, diagnosed as culture-positive sepsis, and admitted to six ICUs of Guangdong General Hospital from October 12th, 2012 to December 1st, 2014 were enrolled. Based on the number of isolated pathogens, patients were divided into polymicrobial infection group (≥two pathogens) and monomicrobial infection group (one pathogen) to investigate the clinical characteristics of patients with culture-positive sepsis and the causative pathogens. Multiple logistic regression was conducted to identify the risk factors for polymicrobial infection. Kaplan-Meier curve was plotted to analyze a 90-day survival rate from the onset of positive blood culture.Results 299 patients with positive blood culture were enrolled. A total of 450 strains of pathogens were isolated including 246 gram-positive cocci (54.67%), 167 gram-negative bacilli (37.11%) and 37 fungi (8.22%). Ninety-one patients had polymicrobial infection, and 208 with monomicrobial infection. Compared with monomicrobial infection group, patients suffering from polymicrobial infection had more advanced age (years: 73.19±18.02 vs. 60.83±18.06,t = -5.447,P = 0.000), also with higher incidence of cerebrovascular diseases [39.56% (36/91) vs. 17.79% (37/208),χ2 = 16.261,P = 0.000] or chronic renal insufficiency [15.38% (14/91) vs. 7.21% (15/208),χ2 = 4.828,P = 0.028], higher incidence of recent hospital stay (≥2 days) within 90 days [73.63% (67/91) vs. 61.54% (128/208),χ2 = 4.078,P = 0.043], longer mechanical ventilation duration [days: 4 (0, 17) vs. 1 (0, 6),U = 7 673.000,P = 0.006], longer length of hospital stay before blood was drawn for culture [days: 21 (7, 40) vs. 9 (3, 17),U = 6 441.500,P = 0.006], and higher incidence of pre-admission intravenous use of antibiotics [84.62% (77/91) vs. 66.83% (139/208),χ2 = 9.989,P = 0.002]. Multiple logistic regression analysis showed that advanced age [odd ratio (OR) = 1.032, 95% confidential interval (95%CI) = 1.015-1.050,P = 0.000], cerebrovascular diseases (OR = 2.247, 95%CI = 1.234-4.090,P = 0.008), prolonged mechanical ventilation (OR =1.041, 95%CI = 1.014-1.069,P = 0.003), and recent hospital stay (≥2 days) within 90 days (OR = 1.968, 95%CI =1.079-3.592,P = 0.027) were the independent risk factors for polymicrobial infection. In the polymicrobial infection group, the length of ICU stay [days: 46 (22, 77) vs. 13 (7, 22),U = 3 148.000,P = 0.000] and hospital stay [days:81 (47, 118) vs. 28 (17, 46),U = 3 620.000,P = 0.000] were significantly longer, and the ICU mortality [65.93%(60/91) vs. 43.75% (91/208),χ2 = 12.463,P = 0.000] and hospital mortality [68.13% (62/91) vs. 45.67% (95/208),χ2 = 12.804,P = 0.000] were significantly higher, and on the other hand the 90-day survival rate was significantly lower than that in the monomicrobial infection group (χ2 = 8.513,P = 0.004).Conclusions The most common pathogen of ICU sepsis is gram-positive cocci. Independent risk factors for polymicrobial infections were found to be advanced age, occurrence of cerebrovascular disease, prolonged mechanical ventilation, and recent hospitalization. Polymicrobial infection is associated with longer length of ICU and hospital stay, as well as higher mortality.

[ ABSTRACT] AIM:To explore whether IL-1βinhibits the oligodendrocyte precursor cell ( OPCs) differentiation and affects axonal myelination.METHODS:One-day-old SD rats were randomly divided into control group and LPS group ( 48 rats in each group) .The rats in LPS group were intraperitoneally injected with 1 mg/kg LPS.The rats in control group were injected with an equal volume of PBS.The rats in each group were further divided into 3 h, 24 h, 3 d, 7 d, 14 d and 28 d subgroups after injection.The expression of IL-1βand IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d was determined by double immunofluorescence and Western blotting.The myelin basic protein( MBP) expression in the rat cor-pus callosum at 14 d, 28 d after injection was also measured.In vitro, primary OPCs culture was performed and divided in-to control group, 30 μg/L IL-1βgroup, 30 μg/L IL-1β+IL-1Ra group and 30 μg/L IL-1Ra group.The expression of MBP in the OPCs induced differentiation for 3 d was observed by double immunofluorescence and Western blotting.RE-SULTS:The expression of IL-1βand IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d after LPS injection was ob-viously increased and the expression of MBP in the rat corpus callosum at 14 d, 28 d in LPS group was obviously decreased compared with control group in vivo.The level of MBP was significantly decreased after IL-1βtreatment for 3 d in vitro. However, IL-1Ra (IL-1R inhibitor) reversed the down-regulation of MBP expression.IL-1βinhibited the expression of p-ERK, ERK over-expression reversed the down-regulation of MBP expression compared with IL-1βgroup.CONCLUSION:IL-1βinhibits the differentiation of OPCs, which may be involved in ERK pathways, thus leading to axonal hypomyelination in the corpus callosum of septic neonatal rats.

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".

Objective: To investigate the function and mechanism of phospholipase C?1 (PLC?1) in cell-matrix adhesion in colorectal cancer. Methods: Highly metastatic colorectal cancer cell line LoVo and lowly metastatic colorectal cancer cell line SW480 were subjected to cell-matrix adhesion assay. U73122 (a specific inhibitor of PLC) and pyrrolidine dithiocarbamate (PDTC) (an inhibitor of NF-?B) were used to study the effect of PLC?1 and NF-?B on cell-matrix adhesion. Furthermore, Western blot and gel electrophoresis mobility shift assay (EMSA) were performed to detect the mechanism of PLC?1 in colorectal cancer cell adhesion to matrix. Results: Inhibition of PLC?1 or NF-?B resulted in reduction of cell-matrix adhesion in a dose-dependent manner in LoVo cells(P

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".
Antineoplastic Agents ; chemistry ; Drug Carriers ; chemistry ; Liposomes ; chemistry ; Polyethylene Glycols ; chemistry

Animals ; Cells, Cultured ; Electrophysiology ; Mice ; Mice, Inbred Strains ; Neurons ; physiology ; Potassium Channels ; physiology ; Spiral Ganglion ; physiology

Child, Preschool ; Humans ; Male ; Nevus, Blue ; pathology ; Skin Neoplasms ; pathology

Objective To explore the possibility of rapamycin to up-regulate radiosensitivity of nasopharyngeal carcinoma (NPC) and its molecular mechanism.Methods In vitro,with untreated cells as the control,NPC cells were treated with rapamycin,irradiation (IR),or both rapamycin and IR.Phosphorylation of S6 and GSK3β,expression of Cyclin D1,clonogenic survival,number of residual γH2AX foci,and cell cycle status between study groups were compared.In vivo,athymic mice bearing CNE1 tumor were similarly treated.Tumor weight,Cyclin D1 and phosphorylated S6 in the xenograft model were compared between study groups.Results The results showed that rapamycin alone decreased the phosphorylation of S6 and glycogen synthase kinase 3 β (GSK3β),and the expression of Cyclin D1 in NPC cells.Thus,rapamycin-treated NPC cells had lower cell viability,higher DNA damage and more G1 arrest than the control,which was reflected by the in vivo study that rapamycin significantly attenuated tumor growth and decreased the levels of Cyclin D1 and phosphorylated S6.Moreover,the combination of rapamycin and IR caused the highest cell death,DNA damage,G1 arrest and tumor regression compared to those treated either alone.Conclusions Rapamycin up-regulate NPC radiosensitivity by inhibiting signal transduction of Akt/mammalian target of rapamycin (mTOR)/S6 pathway and Akt/GSK3β pathway,and by downregulating Cyclin D1 expression.

Objective: To discuss the conversion coefficient of morphine injection with continuous intravenous pump delivery or subcutaneous injection for the patients with advanced cancer pain demanding high dose of opioids.Methods: Using a retrospective survey, the patients with advanced cancer pain demanding high dose of opioids with poor efficacy were divided into 3∶1 group and 2.5∶1 group, and the conversion coefficient of 3∶1 or 2.5∶1 was used for the opioids equivalently conversed to intravenous or subcutaneous injection of morphine.After the conversion, the degree of pain relief, the analgesic efficiency in the conversion process, titration time, daily oral morphine equivalent amount at stable pain, morphine related adverse reactions and the other indicators were studied to evaluate the analgesic effect of morphine injection with different conversion coefficient.Results: There was no statistical significant difference between the two groups in the degree of pain relief, the effective rate of analgesia and the daily oral akministration amount of morphine at sable pain(P>0.05).The adjustment times for morphine in the two groups was (1.57±0.93) and (1.0±0.00), respectively, and the difference was statistically significant (P<0.05).The daily oral administration amount of morphine at stable pain in the two groups respectively was (226.67±69.74) mg and (258.67±101.34) mg;the morphine related adverse reactions were mainly constipation, and there was no significant difference in the incidence (P>0.05).Conclusion: Giving morphine injection to the patients with terminal cancer pain demanding high dose of opioids with poor effect, the use of PCA pump through intravenous or subcutaneous injection can effectively relieve pain.Using the conversion coefficient of 2.5:1 can quickly complete the titration process, and safely achieve the effective analgesia.