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

Objective To report a peliosis hepatic in child and review literature and discuss.Methods Case history was inquired.Physical,labtoratory,imagement and histopathology of liver biopsy(HE staining) were examed.Results A 4-year old girl appeared dermatitis with erythema and herpes at local skin where was bit by insect before onset.The girl appeared fever,cough,then abdominal pain,hepatomegaly,pleural effusion and ascites.Lab examination revealed slight elevation of aspartate transaminase,?-glutamyltranspeptidase and alkaline phosphatase.The liver B-mode ultrasonography and CT scan revealed hepatomegaly with density heterogeneity of the parenchyma.The liver biopsy revealed many small capsule filled with blood cells.Conclusions Clinical characteristics of the disease are fever,upper abdomen pain,janundice,ascites and hepatomegaly.The diagnosis shall be combined with the pathologic biopsy of liver.

Objective To explore the feasibility of excluding oral 75 g glucose tolerance test (OGTT)in pregnant women with fasting plasma glucose (FPG) ＜4.4 mmol/L in middle and late trimester.Methods From February 1,2012 to August 31,2013,18 851 pregnant women without pre-gestational diabetes mellitus who received 75 g OGTT in Maternal and Child Health Hospital of Hubei Province,China,at 24-28 weeks of gestation were enrolled.The criteria for gestational diabetes mellitus (GDM) were FPG ＞5.1 mmol/L and/or 1 h plasma glucose ＞10.0 mmol/L and/or 2 h plasma glucose ＞8.5 mmol/L in OGTT.The values of FPG in predicting GDM were analyzed with receiver operating characteristic (ROC) curve.The differences of detection rates for GDM among women of different ages,women with different FPG levels,and those with or without risk factors of GDM were compared by x2 test and Fisher's exact test.Results The overall detection rate of GDM was 9.11％(1 718/18 851).The detection rate of GDM was lower in women aged ＜ 25 years than women aged 25-,30-and ≥ 35 years [4.77％ (137/2 875) vs 7.76％ (803/10 350),12.43％ (552/4 440)and 19.06％ (226/1 186),respectively,x2=30.53,120.24 and 210.66,all P＜0.01].The sensitivity and specificity were 55％ and 68％,respectively,when the cutoff value of FPG was 4.4 mmol/L,and the Youden index was 0.23 and the area under the ROC curve was 0.61 (95％CI:0.59-0.63,P＜0.01).The sensitivity and specificity were 40％ and 80％,respectively,when the cutoff value was 4.5 mmol/L,and the Youden index was 0.20 and the area under the ROC curve was 0.61 (95％CI:0.59-0.63,P＜0.01).The missed diagnosis rate was lower when the cutoff point of FPG was defined as 4.4 mmol/L.The detection rate for GDM was 3.45％ (384/11 121) in women with FPG ＜4.4 mmol/L,significantly lower than in those with FPG ≥ 4.4 but ＜5.1 mmol/L and ≥ 5.1 mmol/L [8.06％ (561/6 957) and 100.00％ (773/773),x2=183.66 and 7 672.08,all P＜0.01].When FPG was ＜4.4 mmol/L or ≥ 4.4 but ＜5.1 mmol/L,the detection rate for GDM was significantly higher in women with GDM risk factors than in those without [5.09％ (118/2 318) and 10.75％ (184/1 712) vs 3.02％ (266/8 803) and 7.19％ (377/5 245),x2=23.56 and 22.06,P＜0.01].Conclusion OGTT may not be included in GDM screening in the pregnant women with FPG＜4.4 mmol/L and without GDM risk factors in the areas lack of medical resources.

Objective To observe the expression of hypoxia inducible faetor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First, control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber, and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1, 3, 7 and 14 after retinal ischemla-reperfusion, respectively. Results No cells with HIF-la positive expression were observed in the retina of the control group. Ceils with HIF-1α positive expression in the model group outnumbered those in the control group (P < 0. 01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure, which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.

Objective To investigate the clinical and molecular pathological features of dysferlinopathy in China.Methods Four patients with limb-girdle muscular dystrophy2B(LGMD2B)and 4 patients with Miyoshi-type distal muscular dystrophy(MMD)were clinically analyzed, their skeletal muscle were biopsied and immunohistochemical stained.Four cases of each Duchenne-Aran muscular atrophy and myotis were served as controls.Results The clinical situation of dysferlinopathy was characterized by progressive muscle weakness and atrophy, consistent with progressive muscular dystrophy.Histochemical staining revealed muscle fibers degenerating, regenerating and necrosis in a varying degree.Connective tissue was seen proliferated and inflammatory cells infiltrated in the majority of cases.Immunohistochemical staining with anti-dysferlin monoclonal antibody identified the deficiency of dysferlin on the sarcolemma and in the sarcoplasm of 8 cases with dysferlinopathy.Conclusions(1)The clinical and pathological characters of dysferlinopathy are consistent with progressive muscular dystrophy;(2)Anti-dysferlin monoclonal antibody immunohistochemical staining is a reliable method to diagnose dysferlinopathy, which is worth of wide application in clinic.

Objective To explore the changes of S-100 protein(S-100) levels in blood in newborn rats with bilirubin encephalopathy.Methods The model was established by administered bilirubin intraperitoneally(200 mg/kg) in newborn rats.The blood and brains samples were taken from 8 rats at the sequential time points of 6,12,24,48,72 and 96 h after the model established.Eight normal rats were used as the control.The dynamic changes of S-100 were detected by enzyme linked immunosorbent assay(ELISA) and immunohistochemical technique.Results S-100 significantly increased in blood of bilirubin encephalopathy newborn rats compared with controls(P

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.
Cell Nucleus ; Doxorubicin ; analogs & derivatives ; chemistry ; Endosomes ; Formates ; chemistry ; Humans ; Liposomes ; chemistry ; MCF-7 Cells ; Microscopy, Confocal ; Particle Size ; Phosphatidylethanolamines ; Polyamines ; chemistry ; Polyethylene Glycols ; chemistry

OBJECTIVETo discuss the trend of displacement on the side of nondistraction when distraction osteogenesis with unilateral incomplete osteotomy of canine mandible.

METHODSThe method of finite element analysis was used to simulate distraction osteogenesis with unilateral incomplete osteotomy and the displacement of six marked point such as the temporomandibular joint and the angle of mandible and coracoid process and teeth were observed on nondistractional side when the transport disc was distracted with a distance and without a distance.

RESULTSWhen the transport disc was distracted without a distance, the Von Mises stress was 0 in the six marked point of nondisractional side and their displacement in 3 dimensions (X, Y, Z axis) was 0. When the transport disc was distracted with 1 mm width, all marked point had some displacement.

CONCLUSIONWhen distracted and observed from the side of distraction, the mandible at the side of nondistraction has the trend of contrarotation round the center of the transverse ridge mid-point of condyle process on the plane of sagittal, whereas it has the trend of parallel movement approximately in the direction of opposite side on the plane of coronary.

Finite Element Analysis ; Humans ; Mandible ; Osteogenesis, Distraction ; Osteotomy ; Temporomandibular Joint

OBJECTIVEThe study aimed to investigate the relationship between arrhythmia occurrence and nerve remodeling of thoracic spinal cord 1-5 nerves as well as myocardial electrophysiological remodeling in a metal stress rat model.

METHODSThirty SD rats (weight 180-250 g) were randomly divided into control group (n = 10), stress group (n = 10) and fluoxetine group (n = 10, 10 mg/kg i.p. for 3 weeks). Stress model (given by unpredicted chronic mild stress) was established according to Cronli's protocol. Following parameters were observed:(1) ECG waveform change and arrhythmias;(2) tissue field action potential duration (FAPD) of thoracic spinal cord 1-5 and cardiac tissue mapped by microelectrode arrays (MEA) technique;(3) myocardial growth-associated protein (GAP-43), tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) distribution observed by immunofluorescence and confocal laser scanning microscope (LSCM).

RESULTSThree weeks later: (1) The body weight, food intake, consumption of sugar water, the horizontal and vertical movement score, cleaning action of rats were significantly decreased, and fecal grains significantly increased, P-wave, P-R interval, QRS-wave and Q-T interval were significantly prolonged and heart rate was significantly reduced in stress group compared with control group (all P < 0.05). Incidence of ventricular premature beat was 80% in stress group and 0% in control group (P < 0.05). The FAPD of thoracic spinal cord 1-5 nerves [(144.25 ± 12.63)ms vs (79.56 ± 8.01)ms] and of cardiac tissue [LA(122.43 ± 19.34)ms vs (92.59 ± 7.61)ms, RA(149.89 ± 14.68)ms vs (105.18 ± 15.94)ms, LV(162.62 ± 7.04)ms vs (110.45 ± 6.92)ms, RV(152.21 ± 30.49)ms vs (131.06 ± 12.04)ms] were significantly prolonged, FAPD dispersion (FAPDd) significantly increased [thoracic spinal cord 1-5(13.3 ± 9.11)ms vs (9.36 ± 7.01)ms] in stress group compared with the control group. Disarrangement of myocardial cells, proliferation of collagen fiber, infiltration of neutrophil and lymphocytes in the cardiac tissue were also observed and distribution of GAP-43, TH and CHAT was significantly increased in stress group. (2) All these changes could be partly reversed by the treatment with fluoxetine.

CONCLUSIONMetal stress induced cardiac autonomic nerve and myocardial electrophysiological remodeling and ventricular arrhythmia in rats which could be significantly attenuated by fluoxetine in this model.

Animals ; Arrhythmias, Cardiac ; etiology ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Fluoxetine ; therapeutic use ; GAP-43 Protein ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; physiopathology ; Stress, Psychological ; complications ; physiopathology ; Thoracic Nerves ; physiopathology ; Tyrosine 3-Monooxygenase ; metabolism ; Ventricular Remodeling

Adult ; China ; Female ; Hepatitis B ; prevention & control ; transmission ; Hepatitis B Vaccines ; Humans ; Immunization ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Retrospective Studies