With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.
Administration, Oral ; Biological Availability ; Biological Products ; administration & dosage ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; methods ; trends ; Solubility ; Technology, Pharmaceutical ; methods ; trends ; Water

Exosome is a self-secreted phospholipid bilayer nanovesicles, and has shown great potential in drug delivery field due to the important advantages of low immunogenicity and homologous targeting. Phototherapy, mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), utilize light to activate photoactive drug for tumor cell killing. The advanced therapeutic strategy shows low toxic side-effect and non-invasion precise advantages, and thus has made great progress in tumor treatment over the past few years. Therefore, using exosomes as a drug delivery system to deliver phototherapeutic agents can improve therapeutic performances with a reduced side-effect, and further enhance their application potential for clinical tumor therapy. This review focus on the rising cross-subjects field involving exosomes and phototherapy, and mainly introduce the research progress and relative case of exosomes-based delivery system for cancer phototherapy. Additionally, the advantages and challenges of exosome-based phototherapy are also discussed and proposed.

OBJECTIVETo evaluate the efficacy and safety of three different spinal rotation manipulations for the treatment of lumbar disc herniation.

METHODSFrom September 2011 to April 2013,180 patients diagnosed as lumbar disc herniation were randomly divided into seat fixed rotation group (A), lateral position rotation group (B) and supine position rotation group (C) by using a digital table. Finally 10 patients were excluded and dropped, 170 patients were included in the study. There were 57 patients in group A, 57 patients in group B and 56 patients in group C. Baseline demographic characteristics of patients, clinical findings and indexes of health status had no statistically differences among three groups (P > 0.05). The manipulation was performed every other day, and the treatment duration for all patients was 3 weeks. Body pain (BP), Physical function (PF) in SF-36, Oswestry Disability Index (ODI) and adverse reactions were observed statistically 6 weeks, 3 months, 6 months, one year and two years after finishing treatment.

RESULTSBP, PF scores in 3 groups were significantly improved and ODI scores were significantly lower than those before treatment and the differences were statistically significant (P < 0.05); However, there was no significant difference among three groups in the BP, PF and ODI scores (P > 0.05). There were no obvious and serious adverse reactions among these groups.

CONCLUSIONBased on the theory of dislocation of bone joints in TCM, three kinds of spinal rotation manipulations can be used safely for the treatment of lumbar disc herniation, and the efficacy was similar.

Adolescent ; Adult ; Case-Control Studies ; Female ; Humans ; Intervertebral Disc Displacement ; physiopathology ; therapy ; Male ; Manipulation, Spinal ; methods ; Middle Aged ; Rotation ; Treatment Outcome ; Young Adult

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.

Background and purpose:Ionizing radiation(IR) activates the early growth response- I(Egr1) promoter through specific cis-acting sequences termed CArG elements by production of radical oxygen intermediates(ROls).Egr-EG,an expression vector pCIneo containing CArG elements cloned upstream of the cDNA for human recombinant GM-CSF,was used to treat hematopoietic damage due to chemotherapy.Commonly used chemotherapeutic agents can cause tumor cell death by producing DNA damage and generating ROIs.We therefore hypothesized that clinically employed chemotherapeutic agents that increase ROIs could also be employed to activate Egr-EG in a chemoinducible gene therapy strategy.This study was done to explore the chemo-protective effect of the expression of hematopoietic growth factors regulated by Egr-1 promoter on chemotherapy induced damage. Methods:The human GM-CSF cDNA and EGFP cDNA were linked together with internal ribosome entry site(IRES) and then inserted into the eukaryotic expression vector pCI-neo with the Egr-1 promoter(Egr-EG),and was further transduced into human bone marrow stromai cell lines HFCL(HFCL/EG).The HFCL/EG cells were transplanted i.v.into BI6 melanoma in C.B-17 combined immunodeficient(SCID) mice.5-FU was given i.p.on day 3 and 4.The white blood cell amount in peripheral blood,the expression of EGFP and GM-CSF in human stromal cell engrafted in recipient mice were detected by flow cytometry,RT-PCR,Western blot and colony-forming units for granulocytes and macrophages(CFU-GM),respectively.Results:In contrast to the two control groups,HFCL/EG(the Egr-regulatory element-derived expression of GM-CSF gene therapy) resulted in a proportional increase in the number of the white blood cell after chemotherapy,no significant diifferences were found for CFU-GM in bone marrow cells and the inhibition ratio on tumor in recipient mice.Chemotherapy could markedly increase the expression of EGFP and GM- CSF mRNA/protein as compared with that of non-chemotherapy control groups and HFCL group.Conclusion: Chemoinducible GM-CSF gene therapy regulated by Egr-1 promoter can ameliorate the toxic effect on 5-FU chemotherapy-inducible hematopoietic damage.

Objective: To learn the status of knowledge,attitude and behaviors of road traffic safety in primary and secondary school students in Xiacheng District of Hangzhou. Methods: The students of fourth to seventh grade from seven schools in Xiacheng District were selected and surveyed for their knowledge,attitude and behaviors of road traffic safety by self-designed questionnaires. Results: Totally 4 006（99.98%）students completed the survey,who mostly had awareness rates of over 90% in knowledge about safe behaviors when walking,walking across the road and riding a bicycle or an electric bicycle. The awareness rates of"should not run across the road","should not ride side by side"and"should not ride on the motorway"were relatively low,which were 81.65%,85.72% and 82.78%,respectively. About 68.47% of students thought it necessary to wear a helmet when riding a bicycle or an electric bicycle,72.22% of students thought it necessary to wear seatbelt or use child safety seat when taking a car. The two rates were significantly higher in girls than boys and in primary school students than secondary school students（P<0.05）. The top three unsafe behaviors the students did in the past six months were"not wear a helmet when riding a bicycle or an electric bicycle","run across the road"and"ride on the motorway",the rates of which were 86.84%,10.06% and 7.91%,respectively. Conclusion The knowledge of road traffic safety among primary and middle school students in Xiacheng District is mastered well. Interventions should be focused on unsafe behaviors including not wearing a helmet when cycling,riding on the motorway and running cross the road.

Objective: To investigate the pedestrian traffic safety behaviors of primary and secondary school students in Xiacheng District of Hangzhou,and to provide reference for formulating traffic safety strategy. Methods: In October 2015,nine campuses of six schools in Xiacheng District were selected to observe the pedestrian traffic safety behaviors of the primary and secondary school students walking to and from school,such as taking the zebra crossing,observing the traffic condition,running and playing with cellphones when walking across the road. Results: Totally 2 585 students were investigated,and 2 580 students were valid（99.81%）. When walking across the road,1 887 people took the zebra crossing,accounting for 73.14%;71.89% of boys and 74.51% of girls took the zebra crossing,and there was no significant difference（P>0.05）;64.76% and 81.32% of the students took the zebra crossing on the way to school and home,with a significant difference（P<0.05）. When walking across the road,1 683 students people observed the traffic conditions,accounting for 65.23%;63.61% of boys and 67.02% of girls observed the traffic conditions,and there was no significant difference（P>0.05）;64.05% and 66.39% of the students observed the traffic conditions on the way to school and home,with a significant difference（P<0.05）.There were 362 students running across the road, accounting for 14.03%;15.31% of boys and 12.62% of girls ran across the road,and there was no significant difference（P>0.05）;9.26% and 18.68% of the students ran across the road on the way to school and home,with a significant difference（P<0.05）. There were 53 students playing with cellphones when crossing the road,accounting for 2.05%;2.29% of boys and 1.79% of girls played with cellphones,and there was no significant difference（P>0.05）;1.41% and 2.68% of the students played with cellphones on the way to school and home,with a significant difference（P<0.05）. Conclusions Primary and secondary school students have dangerous behaviors when walking across the road. We should focus on the intervention of not taking the zebra crossing and not observing traffic conditions when crossing the road on the way to school,and playing with cellphones on the way home.

To study the effect of cytochrome C on HL-60 cells in vitro and the mechanism of expression changes of relevant apoptotic genes, the inhibition rate of cytochrome C on HL-60 cells was detected by MTT, the morphology of HL-60 cells was observed by light microscopy and fluorescence microscopy, the changes of apoptosis rate and cell cycle were assayed by flow cytometry (FCM), DNA ladder was investigated on electrophoresis, the expression changes of bax and bcl-2 mRNA were examined by RT-PCR, when HL-60 cells were treated with different concentrations of cytochrome C for 24 hours. The results showed that the inhibition rate increased with increase of the cytochrome C concentration within 0 - 150 mg/L; when treated with 0 - 37.5 mg/L cytochtome C for 24 hours, the percentage of apoptotic HL-60 cells increased with the dose increasing, and the typical apoptotic cells and the apoptotic DNA ladder were observed. At the same time, within this range of concentration, the expression of bcl-2 mRNA decreased gradually and the expression of bax increased gradually. When the cytochrome C concentration was higher than 37.5 mg/L, the percentage of apoptotic HL-60 cells not increased, but decreased, while the cells necrosed. The above metioned results suggested that at certain range of concentration of cytochrome C, apoptosis or necrosis can be induced by cytochrome C, and cell cycle arrests at G(1) phase in HL-60 cells, the percentage of apoptotic cells and the changes of expression of bax and bcl-2 depend on the dose of cytochrome C. The mechanism that cytochtome C induced apoptosis in HL-60 cells may be related to the activation of bax and inhibition of bcl-2.
Apoptosis ; drug effects ; Cytochromes c ; pharmacology ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gene Expression Regulation, Leukemic ; drug effects ; HL-60 Cells ; Humans ; Microscopy, Fluorescence ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; bcl-2-Associated X Protein ; genetics

The purpose was to study the responses of AML cell treated with cytochrome C and to explore the influence of cytochrome C on apoptosis of AML cell induced by daunorudicine (DNR). The differentiation of AML cell was detected by Wright-Giemsa staining and NBT test, the apoptosis of AML cell was assayed by flow cytometry and fluorescence microscopy. The results showed as follows: (1) different concentrations of cytochrome C could induce different effects on AML cells. Concentration of cytochrome C for differentiation was 10 microl/ml, for apoptosis was 20 microl/ml, and for necrosis was 40 microl/ml. (2) the apoptosis of AML cells decreased with the administration of cytochrome C in 10.0 microg/ml before treating AML cells with DNR (P < 0.01), but no change was shown with the administration of cytochrome C in 20.0 microg/ml (P > 0.05). (3) in reverse sequence, administrating of cytochrome C in 10 microl/ml and 20 microl/ml after treating AML cells with DNR, two different concentrations of cytochrome C could increase the apoptosis of AML cells (P < 0.01). It is suggested that cytochrome C may probably affect the apoptosis of AML cells induced by DNR.
Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Cytochromes c ; pharmacology ; Daunorubicin ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; pathology ; Microscopy, Fluorescence ; Tumor Cells, Cultured

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Echinococcosis ; surgery ; Female ; Humans ; Lung Diseases, Parasitic ; surgery ; Male ; Middle Aged