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

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 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.

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.

OBJECTIVETo study and analyze the factors affecting the recovery of posterior communicating artery aneurysm-induced oculomotor nerve palsy (ONP).

METHODSThe clinical and follow-up data of posterior communicating artery aneurysm-induced ONP in 23 patients from May 2005 to May 2009 were retrospectively compared. There were 7 male and 16 female with a mean age of 50.4 years. Among the 23 patients, 13 patients underwent endovascular coiling (endovascular group) and 10 patients underwent surgical clipping (surgical group).

RESULTSOf the patients with 2 year of follow-up, 6 patients recovered completely and 7 patients recovered partially in the endovascular group, compared with 6 patients recovered completely and 4 patients recovered partially in the surgical group (P = 0.407). Compared to the patients with preoperative complete ONP, the rate of complete recovery was higher in the patients with preoperative partial ONP, while the results did not reach the significance (P = 0.095). Patients accepted treatment in 14 days since the onset of symptoms recovered significantly than who accepted treatment after 14 days since the onset of symptoms (P = 0.045).

CONCLUSIONSThere is no significant difference in recovery from ONP between endovascular coiling and surgical clipping as treatment for posterior communicating artery aneurysm patients with ONP. Timing of treatment after onset of symptoms is a factor affects the recovery of ONP.

Adult ; Aged ; Embolization, Therapeutic ; Female ; Follow-Up Studies ; Humans ; Intracranial Aneurysm ; complications ; surgery ; therapy ; Male ; Middle Aged ; Oculomotor Nerve Diseases ; etiology ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore the roles of hypertension and serum leptin in obstructive sleep apnea hypopnea syndrome (OSAHS).

METHODSTotally 60 patients with OSAHS (OSAHS group) and 40 age- and body mass index (BMI)-matched non-OSAHS individuals (non-OSAHS group) were enrolled in this study. The neck circumference (NC), waist/hip rate (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), leptin, fasting blood glucose (FBG), triglyceral (TG), cholesterol (Chol), and true insulin (TI) were measured before and after sleep . The correlations between hypertension/serum leptin level and OSAHS were analyzed.

RESULTSThe blood pressure(in the morning), especially DBP was significantly higher in OSAHS group than in non-OSAHS control group (89.75+/-2.04) mmHg vs. (81.63+/-1.91) mmHg, P<0.01. DBP in OSAHS group was positively correlated with serum leptin and apnea hypopnea index (AHI) (r=0.282, P<0.05; r=0.318, P<0.01). Logistic regression analysis showed that BMI (P=0.029), heart rate in the morning (P =0.030), and leptin (P=0.049) were independently correlated with the development of hypertension.

CONCLUSIONSOSAHS may independently affect blood pressure, especially DBP, after waking up. BMIHR in the morning and serum leptin may be the independent correlates of hypertension.

Adult ; Case-Control Studies ; Humans ; Hypertension ; etiology ; Leptin ; blood ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; blood ; complications ; physiopathology

BACKGROUNDBronchial carcinoids are rare malignant neuroendocrine neoplasms. Some issues regarding surgical treatment of bronchial carcinoids remain controversial, including the role of bronchoplastic surgery and necessity of systematic lymphadenectomy.

METHODSThis retrospective study involved 131 consecutive patients surgically treated for carcinoid tumors at Shanghai Chest Hospital between March 1990 and August 2010.

RESULTSEighty-nine (67.9%) of the patients were male, and the mean age was 46 years, ranging from 17 to 81 years. Preoperative fiberoptic bronchoscopy was performed in all patients. Endoscopic biopsy was performed in 100 patients with central tumors, and 70 (70%) patients were diagnosed as bronchial carcinoid. The resections performed consisted of 31 pneumonectomie, 32 lobectomies, 26 bilobectomies, 34 sleeve lobectomies, six bronchoplastic procedures without lung resection, and two segmentectomies. During a median of 87 months follow-up, there were nine recurrences including three local recurrences and 6 distant recurrences. No bronchial recurrences were observed. The 3-, 5- and 10-year overall survival rates of pneumonectom and bronchoplastic surgery (including sleeve lobectomy and bronchoplastic procedure without lung resection) were 93.2%, 81.0% and 69.4%, 97.5%, 91.9% and 70.0%, respectively. Multivariate Cox regression indicated that histology and nodal status were significant independent prognostic factors.

CONCLUSIONSBronchoplastic surgery should be considered whenever possible for central carcinoids. Systematic lymphadenectomy is recommended for bronchial carcinoid patients. Histology and nodal status were significant independent prognostic factors of overall survival of patients with bronchial carcinoid.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoid Tumor ; mortality ; surgery ; Female ; Humans ; Lung Neoplasms ; mortality ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome