To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Immunoglobulin M ; blood ; Liposomes ; administration & dosage ; blood ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Mitoxantrone ; administration & dosage ; blood ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.

Objective To establish high-performance liquid chromatography with electrochemical detector(HPLC-ECD) method for the determination for metanephrine and normetanephrine in 24 h urine, and provide a superior test for the diagnostic of pheochromocytomas over plasma/urine catecholamine.Methods MCX solid-phase cartridge was used for extraction of metanephrine and normetanephrine,HPLC-ECD was used for their measurements.The intra-assay CVs,interassay CVs and recoveries of metanephrine and normetanephrine were also calculated.104 hypertensive patients without pheochromocytomas and 5 pheochromocytomas patients were selected in this study.The concentrations of metanephrine and normetanephrine were compared with the plasma and 24h urinary catecholamines concentrations.Results The intra-assay CV,inter-assay CV and recovery of metanephrine were 5.9%, 7.5%,91.1% respectively;the intra-assay CV,inter-assay CV and recovery of normetanephrine were 6.3%,6.6%,88.5%,respectively.The MN,NMN,plasma CA and urine CA of all pheochromocytomas patients were positive.MN and NMN were negative in controls,while plasma CA and urine CA are false positive in 15 patients and 14 patients in controls,respectively.Conclusions The study establish a fast and accurate method for quantification of metanephrine and normetanephrine in 24 h urine by HPLC-ECD.These findings also prove that it is the best biochemical assays for pheochromocytomas at present.

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

This systematic review aimed to evaluate the efficacy and safety of assisted hatching (AH) performed in couples with advanced maternal age.We searched for randomized controlled trials (RCTs) in electronic databases,including MEDLINE,EMBASE and CENTRAL (from inception to January 2018);in addition,we hand-searched the reference lists of included studies and similar reviews.We included RCTs comparing AH versus no treatment (control).The meta-analysis was performed by RevMan 5.3 software.The search retrieved 943 records and 8 RCTs were included,comprising 870 cycles (n=440 for AH,and n=430 for control).There was no significant difference in the rates of live birth (RR 0.88,95％ CI 0.65 to 1.18,3 RCTs,n=427,I2=0％),clinical pregnancy (RR 1.00,95％ CI 0.83 to 1.19,8 RCTs,n=870,I2=22％),implantation (RR 1.07,95％ CI 0.83 to 1.39,4 RCTs,n=1359,I2=0％),miscarriage (RR 1.13,95％ CI 0.66 to 1.94,2 RCTs,n=116,I2=0％) and multiple pregnancy (RR 0.89,95％ CI 0.31 to 2.52,1 RCT,n=97,I2=not applicable) between the treatment group and control group.No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses.Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Objective? To explore the effects of health education based on theory of planned behavior on treatment compliance among maintenance hemodialysis (MHD) patients. Methods? We selected 68 patients with regular MHD in the First Affiliated Hospital of Zhengzhou University from January 2017 to April 2018 as subjects by convenience sampling, 34 cases in control group and observation group respectively. Control group carried out routine health education. On the basis of that in control group, observation group implemented health education based on the theory of planned behavior for three months. Finally, we compared the treatment compliance before and after intervention, and patient satisfaction with health education after intervention between two groups. Results? Before intervention, there were no statistical differences in the dimension scores and total score of treatment compliance in two groups (P＞0.05). Three months after intervention, the dimension scores and total score of treatment compliance of observation group were statistically higher than those of control group (t=5.711, 5.523, 2.952, 4.396, 6.767;P＜ 0.01). After intervention, patient satisfaction with health education of observation group was 100.00%, higher than that of control group with a statistical difference (χ2=9.067, P＜0.01). Conclusions? Health education based on theory of planned behavior can improve the treatment compliance and satisfaction with health education among MHD patients, which could be widely used in clinical application.

Objective:To explore application effects of PDCA-based nursing management in patients with hematopoietic stem cell transplantation complicated by oral mucositis.Methods:By the convenience sampling method, 120 patients who underwent hematopoietic stem cell transplantation in the First Affiliated Hospital of Zhengzhou University from January 2016 to January 2017 were selected. According to the random number table method, they were divided into the control group and the observation group, with 60 cases in each group. The control group was given traditional nursing management while the observation group was given PDCA-based nursing management on basis of the control group. The occurrence of oral mucositis, the time of complete healing of oral mucositis, the disappearance time of pain due to oral mucositis and satisfaction with nursing service were compared between the two groups.Results:After the intervention, the incidence of mucositis of grade Ⅰ to Ⅳ in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . The time of complete healing of patients with grade Ⅰ to Ⅳ mucositis in the observation group was shorter than that in the control group, and the difference was statistically significant ( P<0.05) . The disappearance time of pain of patients with grade Ⅰ to Ⅳ mucositis in the observation group was shorter than that in the control group, and the difference was statistically significant ( P<0.05) . The satisfaction rate of nursing service in the observation group was 76.67% (46/60) , higher than 53.33% (32/60) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:PDCA-based nursing management can effectively reduce the incidence of oral mucositis in patients with hematopoietic stem cell transplantation, promote the healing of oral mucositis, relieve patients' pain and improve nursing satisfaction.

BACKGROUNDThe use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. Reactive oxygen species (ROSs) play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.

METHODSWe used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst33258 staining and measurement of lactate dehydrogenase (LDH) release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay.

RESULTSThe results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 microg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.

CONCLUSIONChrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Cell Line ; Cell Survival ; drug effects ; Doxorubicin ; pharmacology ; Flavones ; Flavonoids ; chemistry ; pharmacology ; Glutathione Peroxidase ; metabolism ; HeLa Cells ; Heart ; drug effects ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Molecular Structure ; Myocytes, Cardiac ; drug effects ; Rats ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

Objective:To explore the relationship between single nucleotide polymorphism (SNP) rs4977574 in CDKN2B-AS1 gene and female premature coronary artery disease (pCAD) occurrence. Methods: Our research included 2 groups: pCAD group, n=226 consecutive patients≤65 years of age and Control group, n=79 subjects with matched age,without CAD. The genotype of CDKN2B-AS1 SNP rs4977574 was detected by SNaPshot. Blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), uric acid (UA), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were examined; relationships between rs4977574 polymorphism and the above parameters were assessed. Results: Compared to Control group, pCAD group had increased blood levels of TG, UA, FPG and HbA1c, P<0.05. With adjusted age, body mass index (BMI), relevant disease history and risk factors, elevated HbA1c (HbA1c>6.2%) obviously increased the risk of female pCAD occurrence (OR=3.35, 95%CI 1.41-8.00, P=0.006). The genotype and allele frequency of rs4977574 were different between pCAD group and Control group, P<0.05. Compared to Control group, pCAD group had the higher frequency of G allele(OR=1.24, 95%CI 1.05-1.48, P=0.019); further analysis found that rs4977574 polymorphism was related to high HbA1c. Compared to AA genotype, GG+GA genotype had the increased incidence of high HbA1c(OR=2.08, 95%CI 1.11-3.89, P=0.022). Conclusion: CDKN2B-AS1 SNP rs4977574 was related to female pCAD occurrence and it was also related to high HbA1c.

Background The use of doxorubicin(DOX)is limited by its dose-dependent cardiotoxicity.Reactive oxygen species (ROSs)play an important role in the pathological process of DOX-induced cardiotoxicity.The aim of this study was to evaluate the protective effect of chrysoeriol,a flavone compound,against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.Methods We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)assay,Hoechst33258 staining and measurement of lactate dehydrogenase(LDH)release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells.To find out the mechanism of this protective effect,we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GPx).Furthermore,we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTI assay.Results The results of MTT assay,Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death.Chrysoeriol at a dose of 20 pg/ml notably reduced intracellular ROS,decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels.Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.