The preparation method, serum stability, efficiency of cellular uptake and apoptosis induction of the cell penetrating peptide TAT and cleavable PEG co-modified liposomes loaded with paclitaxel (C-TAT-Lipo) were investigated. The best preparation procedure was performed by orthogonal test based on single factor screening method. First, the paclitaxel (PTX)-loaded liposomes were prepared by filming-rehydration method, evaluated with entrapment efficiency and polydispersity index. The morphology of C-TAT-Lipo was characterized by transmission electron microscopy. Turbidity variations were monitored in the presence of fetal bovine serum (FBS) to evaluate the serum stability of the liposomes developed here. Next, the efficiency of cellular uptake of different Rho-PE-labeled liposomes on B16F1 cells in vitro was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry. The quantitative analysis of apoptosis induced by different PTX-loaded liposomes was performed by Annexin V-FITC/PI double staining. The optimal formulation was as follows: Chol : lipid: 1 : 8 (molar ratio); drug : lipid: 1 : 40 (mass ratio); lipid concentration: 3 mmol x L(-1); temperature of hydration: 25 degrees C. The mean size and polydispersity index of C-TAT-Lipo were about (97.97 +/- 3.68) nm and 0.196 +/- 0.037, the zeta potential was (-0.89 +/- 0.45) mV, the entrapment efficiency of paclitaxel was (90.16 +/- 1.53)%. The particle sizes did not exhibit significant variations in 50% FBS over 24 h at 37 degrees C. The efficiency of cellular uptake of the C-TAT-Lipo increased 1.40 fold following the cleavage of PEG. Apoptosis analysis showed 59.3% increase of the apoptosis and necrosis profile of C-TAT-Lipo after the detachment of PEG shells, which was markedly higher than that of N-TAT-LP with or without glutathione and SL, respectively. The results indicate that the C-TAT-Lipo is successfully prepared by filming-rehydration method and shows significant antitumor activities.
Animals ; Annexin A5 ; Apoptosis ; Cell Line, Tumor ; Cell-Penetrating Peptides ; pharmacology ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Liposomes ; chemistry ; Melanoma, Experimental ; Mice ; Microscopy, Confocal ; Paclitaxel ; pharmacology ; Particle Size ; Polyethylene Glycols ; chemistry

Objective: To investigate the status of electronic cigarette use among adolescents in Ningxia Hui Autonomous Region, and to provide evidence for tobacco control in adolescents. Methods: Based on the 2019 National Youth Tobacco Epidemic Monitoring Program, multistage proportional sampling method was used to select middle school students from Ningxia Hui Autonomous Region. A questionnaire revised by Chinese CDC was used to collect the general information, the cognition and use of electronic cigarettes, and the access to advertising of electronic cigarettes and related products. Results: Totally 9 019 questionnaires were distributed, 8 401 valid ones were recovered, and the response rate was 93.2%. The rates of electronic cigarette use and attempt among students were 4.3% and 13.4%. The rates of electronic cigarette use and attempt in male students were 7.7% and 22.9%, which were higher than that in female students (0.8% and 3.8%, P<0.05) . The rates of electronic cigarette use and attempt varied in different schools ( P<0.05 ), which were higher in vocational high school students ( 11.5% and 26.8% ). Among 246 students who used electronic cigarettes, 30.1% did not thought electronic cigarettes contained nicotine, while 60.2% did not know whether electronic cigarettes contain nicotine. In the past 30 days, 27.0% of the students had seen the advertisements of electronic cigarettes and related products, mainly through TV, store, supermarket, convenience store, grocery store, electronic cigarette experience store or retail store. Conclusions The rates of electronic cigarette use and attempt among adolescents in Ningxia Hui Autonomous Region are 4.3% and 13.4%. Boys and vocational high school students have higher rates. Students generally know electronic cigarette and have more access to it.

Background Researches showed that multifocal electroretinogram (mfERG) is able to assess the retinal function in the eyes with acute Vogt-Koyanagi-Harada ( VKH ) syndrome. But the mfERG characteristics of convalescence stage of VKH are still below clear. Objective Present study was to compare and follow up the variation process of visual acuity and mfERG in acute and recovery stages of VKH syndrome. Methods This was a clinic-based retrospective study. Visual acuity, mfERG and fundus fluorescence angiography ( FFA ) were recorded from 35 eyes of 18 acute VKH cases. The period of follow-up in recovery stage lasted about 18 months with the repetitive recording results for 4 times. Results In this study, the visual acuity range in acute stage VKH was 0. 01 to 1.0, and 91.4% (32/35 eyes) was below 0.6. Compared with normal control group, the visual acuity was significantly decreased (P＜0.01). The response densities (amplitudes) of N1 ,P1 waves of the first-order kernel were significantly lowed in all the 6 rings,and the implicit times of 1-4 rings of both waves were significantly prolonged in acute VKH eyes(P＜0. 05). The abnormalities of retinal function showed a regional difference at the posterior pole retina with the dominant change in the first ring,showing a cutting off78% in the P1 amplitude. The abnormal degree of mfERG was more serious as the the increase of retinal eccentricity. In 2 months of convalescence after glucocorticosteroids therapy,the range of visual acuity were 0. 1-1.2 ,and the amplitudes of N1, P1 of 1-2 rings were greatly elevated in comparison with acute on-set (P＜0. 05 ). However, there was still a remarkable difference in the amplitudes of from 1 through 6 rings,comparing with normal. The response density of P1 wave from whole recording region was only 44% of normal. Though the visual acuity was stable during the follow-up duration, a decreasing tendency in N1 and P1 amplitudes were seen. The implicit times of both wave shortened only in 1-3 rings in recovery stages of VKH (P＜0.05). Conclusion VKH syndrome cause serious damage of posterior retinal function.Macular region is the site with greater retinal functional lesion and restore before and after medication. This hardly recovery of retinal function can last over one and half year,even satisfied visual acuity is stable after proper treatment.

AIM:To investigate the changes of choroidal thickness in patients with severe non-proliferative diabetic retinopathy (NPDR) after vitreous injection of ranibizumab,and to analyze the relationship between the thickness of choroid and the visual acuity of the patients.METHODS:Eighty patients with severe non-proliferative diabetic retinopathy were selected from January 1,2014 to January 1,2017.All patients were divided into observation group and control group according to the random number table,40 cases in each group.The control group was treated in a conventional manner,and the observation group was injected with ranibizumab in the vitreous.The thickness of the choroid in the macular area and the thickness of the retinal neuroepithelium in the macular area were compared between the two groups before and after treatment.The changes of the corrected visual acuity were analyzed at 1mo before and after treatment.The relationship between the thickness of the choroid and the thickness of the retinal neuroepithelium and the best corrected visual acuity were compared.The complications and adverse events were compared between the two groups after 6wk of treatment.RESULTS:The thickness of the choroid and the retinal neuroepithelium in the macular area before were 219.57± 51.24μm and 474.76 ± 95.56μm,respectively,in the observation group and the control group,217.56± 50.36μm and 473.27 ± 96.48μm,respectively.The thickness of the choroid and the thickness of the retinal neuroepithelium in the macular area after treatment were 180.15±42.06μm and 382.18±84.26,202.48±48.28μm and 407.88± 44.25μm,respectively.The difference between the two groups was statistically significant (P＜0.05).The best corrected visual acuity in the observation group and the control group were 0.47±0.19 and 0.53±0.25 respectively (P＜0.05).There was a positive correlation between the choroidal thickness and the best corrected visual acuity in the macular fovea (regression coefficient=1.12,S=0.48,OR=1.376,P＜ 0.05).There was a positive correlation between retinal neuroepithelial thickness and best corrected visual acuity in the macular area (regression coefficient =0.95,S=0.27,OR=1.020,P＜ 0.05).There were 2 eyes (5％) with subconjunctival hemorrhage,1 eyes (2.5％) of glaucoma,1 eyes (2.5％) of vitreous hemorrhage,0 of choroidal detachment,retinal detachment in 0 in observation group at 6wk after treatment.There were 4 eyes (10％) with subconjunctival hemorrhage,2 eyes (5％) of glaucoma,2 eyes of vitreous hemorrhage (5％),2 eyes of choroidal detachment (5％),retinal detachment in 2 eyes (5％) in the control group,and the difference between the two groups on the complications and adverse reactions was statistically significant (P＜0.05).CONCLUSION:The choroidal thickness of patients with macular edema in severe non-proliferative diabetic retinopathy is correlated with the best corrected visual acuity.Intravitreal injection of ranibizumab can effectively reduce the macular fovea choroidal thickness,reduce macular edema and improve vision,and less complications.

AIMTo investigate the influence and mechanisms of 17beta-estradiol on the CTP: phosphorylcholine cytidylyltransferase (CCT) activity from cultured lung explants without serum.

METHODSWe detected the amount of [M-14C] choline incorporation into phosphatidylcholine so as to reflect CCT activity by liquid scintillation.

RESULTS(1) 17beta-estradiol increased the CCT activity in dose-dependence and time-dependence. (2) Both the protein kinase C inhibitor H-7 and calmodulin antagonist W-7 abolished the stimulatory effect of 17beta-estradiol (3 x 10(-6) mol/L) on the CCT activity.

CONCLUSION17beta-estradiol can increase CCT activity in cultured lung explants, its mechanism is related to protein kinase C and calmodulin.

Animals ; Calmodulin ; metabolism ; Choline-Phosphate Cytidylyltransferase ; metabolism ; Culture Media, Serum-Free ; Estradiol ; pharmacology ; In Vitro Techniques ; Lung ; drug effects ; enzymology ; Male ; Protein Kinase C ; metabolism ; Rats ; Rats, Wistar

OBJECTIVE: Explore the affecting factors of mentally prisoner's competency to serve a sentence (CSS), establish the base of quantitative study of CSS. METHODS: Firstly, the researchers compile a questionnaire named legal-psycho ability of competency to serve a sentence questionnaire, then the researchers scaling the object with RTHD, and ask all object complete the questionnaire. there a hypothesis, that the object who are cured in cured ward is incompetent to serve a sentence (ISS), and the other who are stay in rehabilitated ward is competent to serve a sentence (CSS). RESULTS: There are 185 object admitted the study, the ISS group the CSS group have significance between psychiatric and legal aspects. CONCLUSION At the influence of psychiatric symptoms, the mentally prisoner's competency to serve a sentence had been impaired, and they should been transferred from prison to hospital.
Adult ; Expert Testimony/standards* ; Female ; Forensic Psychiatry ; Humans ; Male ; Mental Competency ; Mental Disorders/psychology* ; Mentally Ill Persons/psychology* ; Middle Aged ; Prisoners/psychology* ; Surveys and Questionnaires

OBJECTIVETo investigate the changes in the activity of Escherichia coli asparaginase (L-asp) and the concentration of asparagines (ASN) in the plasma of the acute lymphoblastic leukemia (ALL) children receiving L-asp containing chemotherapeutic protocol to explore more reasonable usage of L-asp in the treatment of childhood ALL.

METHODSL-asp containing hemotherapy regimen of VDLP was used, in which L-asp (10,000 U/m(2)) was administered intravenously every other day for 10 doses in 15 children with ALL. A total of 340 peripheral blood samples were collected at scheduled time points during the therapy and plasma L-asp activity (by spectrophotometric assay) and asparagines concentration (by RP-HPLC) were measured.

RESULTSDuring the administration of L-asp, the plasma L-asp activity was increasing gradually peaked after eight doses and then decreased gradually, while the plasma concentration of asparagines maintained in complete or nearly complete depletion status. After the therapy courses finished, a plasma L-asp activity above 100 U/L with asparagines almost complete depletion status was lasting for about seven days.

CONCLUSIONThe current L-asp containing chemotherapeutic protocols in which L-asp was administered in a dose of 10 000/m(2) intravenously every other day, are efficient enough for the depletion of plasma ASN.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; blood ; pharmacokinetics ; therapeutic use ; Asparaginase ; administration & dosage ; blood ; pharmacokinetics ; Asparagine ; blood ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Humans ; Infusions, Intravenous ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Treatment Outcome

To investigate the influence of vasoactive intestinal peptide (VIP) on chemotaxis of bronchial epithelial cells (BECs). Rabbit chemotactic migration of primary BEC was assessed in a blind-well Boyden chamber. Radioimmunoassay and radio-ligand affinity analysis were used for determining VIP secretion and vasoactive intestinal peptide receptor (VIPR) expression. The results showed: (1) the method for determining chemotaxis of BECs by using insulin as chemotactic factor was stable and reproducible (r=0.9703, P<0.01). (2) VIP (0.001-1 micromol/L) elicited chemotaxis of BECs which was substantial and concentration-dependent. The effects of VIP were inhibited by W-7 and H-7 (P<0.01). (3) Heat stress enhanced the secretion of VIP (P<0.01) and upregulated the expression of VIPR on BECs (P<0.05). These results indicate that VIP in the lungs may play an important role in the repair of damaged epithelium, accelerating restoration of the airway to its normal state. Calmodulin and protein kinase C may be involved in the signal transduction of VIP effects.
Animals ; Bronchi ; cytology ; Cells, Cultured ; Chemotaxis ; drug effects ; physiology ; Epithelial Cells ; drug effects ; physiology ; Female ; Insulin ; pharmacology ; Male ; Rabbits ; Receptors, Vasoactive Intestinal Peptide ; biosynthesis ; Vasoactive Intestinal Peptide ; pharmacology

OBJECTIVETo explore the impacts of electroacupuncture on embryo implanted potential and its molecular mechanism in the patients with infertility of different symptom complex.

METHODSAmong the patients with infertility treated with electroacupuncture and in vitro fertilization and embryo transplantation (IVF-ET), 82 cases of kidney deficiency (group A), 74 cases of liver qi stagnation (group B) and 54 cases of phlegm dampness (group C) were selected. All of the patients in three groups received long-program ovarian hyper-stimulation. Additionally, electroacupuncturecan was applied before controlled ovarian hyper-stimulation (COH) and in the process of ovarian hyper-stimulation. The levels of human leukocyte antigen-G (HLA-G) in the serum were determined on the 2nd day of the menstruation (M2), on the day of human Chorionic Gonadotropin (hCG) injection and on the day of embryo transplantation in the culture solution in three groups separately. The fertilization rate, implantation rate and clinical pregnancy rate were observed for the patients in three groups.

RESULTSThe levels of HLA-G in the serum on hCG injection day and in the culture solution on embryo transplantation day in group A and B were significantly higher than those in group C (all P < 0.05). But, there was no significant difference in serum HLA-G levels on M2 day among three groups. The high-quality embryo rate in either group A (73.6%, 352/478) or group B (70.6%, 379/537) was higher significantly than that in group C (54.2%, 208/384) separately, presenting statistical significant difference (all P < 0.01). But there were no significant differences in clinical pregnancy rate, fertilization rate and cleavage rate among three groups.

CONCLUSIONElectroacupuncture can increase the contents of HLA-G in the body and the level of HLA-G secreted in embryos for the patients in the process of IVF-ET. Eventually, the pregnancy outcome and the pregnancy rate are improved. The clinical effects of electroacupuncture for the patients of kidney deficiency and liver qi stagnation are better than those for the patients of phlegm dampness.

Chorionic Gonadotropin ; administration & dosage ; Electroacupuncture ; Embryo Implantation ; Embryo Transfer ; Female ; Fertilization in Vitro ; HLA-G Antigens ; blood ; Humans ; Infertility ; blood ; drug therapy ; physiopathology ; therapy ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate

Aim To demonstrate that bigelovii E,one of the triterpenoid compounds isolated from Salicornia bigelovii Torr. ,induced apoptosis and inhibited prolif-eration of human breast cancer cells MCF-7. Methods MTT and Clonogenic were used to detect the anti-proliferative effect of bigelovii E on human tumor cells. Hoechst 33258 staining was used to observe the chan-ges of cell morphology in the treatment with bigelovii E. The effect of bigelovii E on cell apoptosis,cell mi-tochondrial membrane potential and the ROS level was analyzed by flow cytometry. The expression of mito-chondrial apoptotic pathway and its regulated proteins were analyzed by Western blot. Results Bigelovii E was most sensitive to MCF-7;bigelovii E had lower toxicity to normal cells HLF1;bigelovii E inhibited the colony formation of breast cancer MCF-7;the apoptosis pattern induced by bigelovii E was detected by Hoechst 33258;Western blot showed that bigelovii E could down-regulate the phosphorylation of mTOR,p70S6K and 4-EBP,up-regulate the expression of Bcl-xl and Mcl-1 proteins,promote the mitochondrial apoptosis pathway,reduce the mitochondrial membrane poten-tial,and induce ROS,leading to mitochondrial func-tion damage,and ultimately inducing apoptosis. Con-clusion Bigelovii E regulates mitochondrial apoptosis pathway through mTOR pathway,induces apoptosis and has a good anti-tumor effect.