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

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".

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.

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

Abstract LRR-RLKs plays an important role in multiple signal transduction in plant.One full-length cDNA encoding a LRR-RLKs homologue was isolated from maize through in silico cloning and named as ZmLRRPK1(GenBank accession:EU873320).The predicted ZmLRRPK1 protein has 594 amino acids with an estimated molecular mass of 66kDa and an isoelectric point of 5.42.ZmLRRPK1 has the typical domain of LRR-RLKs.RT-PCR analysis indicated that ZmLRRPK1 expression was induced by ABA,mannitol and salt in coleoptiles of maize and kept high level during 24 hours.

Objective: To establish an efficient expression system for human truncated insulin like growth factor 1 〔Des(1 3)IGF1〕as fusion protein in Escherichia coli(E.coli). Methods: The cDNA of Des(1 3)IGF1 was cloned into an fusion protein expression plasmid, pMTY4, using gene recombinant technique. The protein was purified by ion exchange chromatography and identified by SDS polyacrylamide gel electrophoresis, radioimmunoassay(RIA), N terminal amino acid sequence and biological activity. Results: A prokaryotic expression vector was constructed and the fusion protein containing MS2 polymerase fragment, thrombin recognition site and human Des(1 3)IGF1 was expressed in E.coli at high level. It was showed that the purified recombinant Des(1 3)IGF1 released from the fusion protein after digestion with thrombin was identical to the native Des(1 3)IGF1.Conclusion:This is an effective method for obtaining human recombinant Des(1 3)IGF1 and it is very important for further study of Des(1 3)IGF1.

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.

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

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

Objective To investigate the characteristics of children′s recurrent abdominal pain(RAP) with gastroscopy and analyze the etiology.Methods Three hundred and thirteen children were investigated with gastroscopy.Gastric antrum mucosa was taken for histo-pathology and the determination of helicobacter pylori(Hp) antibody.Results Ninty-nine point six eight percent of the cases had lesions under the gastroscope.The former 4 cases had chronic superficial gastritis(CSG),CGS and bile reflux,CGS and duodenitis,CGS and bulb ulcer,and Hp infection rate was 31.36%,25%,38.64%,60.61%.Hp infection rates of active gastritis and inactive gastritis were 92% and 23.19%,which showed significant differences in 2 groups(P