Objective To prepare stable silybin oral microemulsion. Methods The formulation of the silybin oral microemulsion was optimized by the combination of surface tension measure, pseudo-ternary phase diagram drawing and orthogonal design. Results Microemulsion type was identified. Average particle diameter was measured. Distribution of silybin in microemulsion was measured by ultracentrifugation. The centrifugalization and influencing factors experiment of microemulsion were carried out,which could keep homogeneous and stable for three months on the storage condition of room temperature. Meanwhile,the influence of high-temperature and illumination was a little. Conclusion Stable oral microemulsion silybin can be prepared in this formulation, with fine-looking and desirable stability which is better for the further studies.

Objective To explore the value of urinary N-terminal telopeptide of type Ⅰ collagen (uNTX) combined with bone scintigraphy (BS) for the diagnosis of bone metastases.Methods A total of 227 patients suspected of bone metastases by BS were selected from Jan to May of 2012.UNTX was tested for each subject.The threshold of uNTX was chosen as 65 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr) for the diagnosis of bone metastasis.Patients with uNTX greater than 65 nmol BCE/mmol Cr would be diagnosed as having bone metastasis.Other examinations (CT,MRI,PET/CT or bone biopsy) were also performed to confirm the diagnosis.The uNTX values of benign and malignant bone lesions were compared using two-sample t test.The diagnostic efficacy of uNTX combined with BS was evaluated.A ROC curve was analyzed to evaluate the cut-off value of uNTX for the diagnosis of bone metastasis.Results The mean value of uNTX of all 227 patients was (84.30± 13.29) nmol BCE/mmol Cr,which was significantly higher than the upper limit of normal range (t =21.875,P＜0.01).Using 65 nmol BCE/mmol Cr as the threshold,197 cases were diagnosed as with and 30 without bone metastases,in which 188 and 27 were respectively confirmed by other examinations.The mean uNTX was (88.73 ± 8.37) and (60.76± 9.14) nmol BCE/mmol Cr in patients with and without bone metastases,respectively (t =-18.134,P＜0.01).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index of uNTX combined with BS were 98.4％ (188/191),75.0％ (27/36),95.4％ (188/197),90.0％ (27/30),94.7％ (215/227) and 73.4％ respectively.The cut-off value by ROC curve analysis was 78.88 nmol BCE/mmol Cr and the area under the curve was 0.982.Using 78.88 nmol BCE/mmol Cr as threshold,the corresponding sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index were 97.4％(186/191),94.4％(34/36),98.9％(186/188),87.2％(34/39),96.9％(22/227) and 91.8％ respectively.Conclusions Using the cut-off value of 78.88 nmol BCE/mmol Cr,uNTX may have clinical value in helping the differential diagnosis of bone scintigraphy for patients suspected of metastatic bone disease.

OBJECTIVE:To establish a method for the contents determination of 9 components in Guizhi decoction,and com-pare the effects of traditional decoction method and the extracting machine decoction method on these contents in Guizhi decoction. METHODS:HPLC was performed on the column of Agilent Zorbax SB-C18 with mobile phaseof acetonitrile- 0.1% phosphoric ac-id(gradient elution)at a flow rate of 1.0 ml/min,the detection wavelength was 230 nm,254 nm and 280 nm,the column tempera-ture was 25℃,and the injection volume was 10μl. RESULTS:The linear range was 0.410 2-210.0μg/ml for gallic acid(r=0.999 9), 0.994 0-254.5μg/ml for albiflorin(r=0.999 9),1.636 0-1 675.0μg/ml for paeoniflorin(r=0.999 9),0.988 3-506.0μg/ml for liquiri-tin(r=0.999 6),0.987 3-31.59 μg/ml for coumarin(r=0.999 5),0.486 8-124.6 μg/ml for cinnamic acid(r=0.999 5),2.458 0-314.6μg/ml for cinnamaldehyde(r=0.999 5),0.034 3-1.096 μg/ml for 2-methoxy cinnamaldehyde(r=0.999 8),and 1.711 0-219.0 μg/ml for glycyrrdhizic acid (r=0.999 7);RSDs of precision,stability and reproducibility tests were lower than 5%,recoveries were 93.56%-103.19%(RSD=4.00%,n=9)、101.51%-107.32%(RSD=2.21%,n=9)、95.08%-103.76%(RSD=2.87%,n=9)、100.82%-105.73%(RSD=1.85%,n=9)、85.08%-89.12%(RSD=1.40%,n=9)、92.31%-99.12%(RSD=2.71%,n=9)、99.17%-102.32%(RSD=1.24%,n=9)、100.15%-103.98%(RSD=1.18%,n=9)、99.93%-102.61%(RSD=1.03%,n=9). The content of total effective components from the extracting machine decoction method was 4 565μg/g,that from the traditional decoc-tion method was 2 742 μg/g.CONCLUSIONS:The method is simple,stable and reproducible,and can be used for the simultaneous determination of 9 componentsin Guizhi decoction. The contents of gallic acid,albiflorin and 2-methoxy cinnamaldehyde are first re-ported. The total effective components from the extracting machine decoction method are higher than that from the traditional decoc-tion method.

Objective To analyze the clinical results of modified N-butyl 2-cyanoacrylate skin adhesive in the application of facial trauma.Methods A total of 687 patients had been analyzed retrospectively from August 2009 to July 2014,and all the wounds of these patients had not obtained the anatomical repositioning after pure manual reduction with tissue glue or pure stitches.Improved tissue adhesive method was as follows:point coating,decomposition and glue with stitches.Results Anatomical repositioning was obtained in 685 wounds of 687 cases with improved tissue adhesive method.Infection occurred in the wounds of 2 cases (0.29％),but no other complications occurred in all patients.During postoperative 3 months of follow-up,clinical results were satisfactory for all patients.Conclusions The improved method of tissue glue has fewer postoperative complications,beautiful and more satisfatory appearance,economic,safer and reliable in the application of facial trauma.

Aim To explore the effect of pharmacolog-ical activation of serotonin 5-HT2C receptor (5-HT2C R) on naloxone-precipitated withdrawal in morphine-de-pendent mice. Method EthoVision Noldus video tracking system was used to record the effect of 5-HT2C R agonist WAY on locomotor activities and behavioral performances in mice.Results Selective 5-HT2C R ag-onist WAY (0.5,0.75 or 1 .0 mg·kg -1 ,i.p.)a-lone did not alter the locomotor activities as determined by distance traveled and velocity (all P values >0.05).Chronic morphine treatment induced depend-ence in mice as demonstrated by increases in distance traveled,velocity and jumping behavior.WAY (0.5, 0.75 or 1 .0 mg·kg -1 ,i.p.)and clonidine (0.2 mg ·kg -1 ,i.p.)significantly ameliorated naloxone-pre-cipitated withdrawal symptoms,including burrowing, jumping,body grooming,rearing,“wet dog”shakes, head shakes,face grooming,penile grooming,scratch (all P values <0.05).Conclusion Pharmacological activation of 5-HT2C R ameliorates naloxone-precipitated withdrawal symptoms in morphine-dependent mice.5-HT2C R may be a novel target to develop therapeutic ap-proach against morphine physical dependence,craving and relapsing.

Stem cells and progenitor cells are the cells of origin for multi-cellular organisms and organs. They play key roles during development and their dysregulation gives rise to human diseases such as cancer. The recent development of induced pluripotent stem cell (iPSC) technology which converts somatic cells to stem-like cells holds great promise for regenerative medicine. Nevertheless, the understanding of proliferation, differentiation, and self-renewal of stem cells and organ-specific progenitor cells is far from clear. Recently, the Hippo pathway was demonstrated to play important roles in these processes. The Hippo pathway is a newly established signaling pathway with critical functions in limiting organ size and suppressing tumorigenesis. This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.
Animals ; Cell Differentiation ; Cell Proliferation ; Drosophila ; Drosophila Proteins ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Mesenchymal Stem Cells ; cytology ; metabolism ; Neoplastic Stem Cells ; cytology ; metabolism ; Nuclear Proteins ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Signal Transduction ; Stem Cells ; cytology ; metabolism ; Transcription Factors ; metabolism

Background and purpose:Hepatocellular carcinoma(HCC) is one of the most common malignancies in the world,It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection is considered the best curative option,the 5-year survival rate could reach 50%,especially in the patients with lesions less than 5 cm in diameter and good residual liver function.However curative surgery is feasible for only about 20% of patients.Transcatheter arterial chemoembolization(TACE) has been demonstrated that its short-term curative effect is better than the other nonsurgical treatments.However,it has not provided any survival benefit.Many studies have been done to improve the overall therapeutic effects of HCC with multi-modality approaches.The purpose of our trial was to evaluate the effects of TACE combined with 3-dimensional conformal radiation therapy(3-DCRT) for primary hepatic carcinoma.Methods:90 patients with primary hepatic carcinoma were randomly divided into two groups :45 were treated with 3-DCRT plus TACE and the others were treated with TACE alone.For TACE,80-120 mg cisplatin and 1 000 mg 5-Fluorouracil or 30 mg hydroxycamptothecine)were perfused into the hepatic arteries,then 50-100 mg adriamycin(or epirubicin) or 16 mg mitomycin C and iodized oil 10-30 ml were given to embolize the hepatic arteries,and followed by 1-2 mm gel form particles.TACE of 1-3 sessions was given to both groups.For the combined group,3-DCRT was given by 6MV X-ray.The patients with planned target volume(PTV) lesser than 512 cm~(3) received a total dose of 45-56 Gy,4.5-7 Gy per fraction,and the patients with PTV larger than 512 cm~(3) received a total dose of 45-56 Gy,2.5-4.5 Gy per fraction,5 times every week.Results:The response rates (CR+PR)of 3-DCRT plus TACE group and TACE alone group were 91.1% and 60%,respectively(?~(2)=11.79,P

Objective:To investigate the effects of ursolic acid (UA) on the proliferation and differentiation of osteoclasts (OC), and to explore its role in orthodontic force-induced root resorption and its relationship with OC.Methods:The mononuclear / macrophage cells RAW264.7 were induced to the OC.Tacrolimus acid phosphatase (TRAP) staining and bone resorption lacunae observation were used to identify the induction.CCK-8 method was used to select the appropriate concentration of UA for RAW264.7 cell-free biotoxicity and to observe its effect on the proliferation and differentiation of RAW264.7.In experimental groups, UA with gradient concentrations (1.0,2.5,5.0,10.0,20.0and 40.0 μmol·L-1)were added.UA was not added in control group.Results:The TRAP staining and bone resorption lacunae observation showed that after the RAW264.7 cells were induced for 5 d, the TRAP staining positive cells were found;the resorption lacunae were rounded,and oval, etc,the bottom wall was coarser,and the boundary was clear,which indicated that the RAW264.7 cells were successfully differentiated into the osteoclasts.The CCK-8 detection results showed that high concentration of UA (> 10.0 μmol·L-1) significantly inhibited the proliferation of OC;the appropriate concentration of UA (5.0 μmol·L-1) was in the biological safety concentration range and could inhibit the OC proliferation;low concentration of UA (<2.5 μmol·L-1) had no effect.Conclusion:RANKL can induce the differentiation and maturation of RAW264.7 cells.UA is correlated with the proliferation and differentiation of OC;UA has inhibitory effect on OC at the appropriate concentration (5.0 μmol·L-1) in a time-dependent manner.

Objective To conduct a retrospective study about drug-induced hyperthermia (DIH) based on DIH data obtained in medical practice,and elucidate the relationship between DIH incidence and antibacterials overuse.Methods To investigate successively the medical records of inpatients from orthopaedics department in Fudan university affiliated Jinshan hospital at two different periods,and data of DIH cases were extracted to perform a comparative study.The period for 229 effective cases of group Ⅰ was from Feb.1 to Apr.30,2011,before significant improvement on antibacterials use.The period for 342 effective cases of group Ⅱ was from Jul.1 to Sep.30,2012,after the effective enforcements of regulation on antibacterials use.Inclusion criteria for DIH were:①an oral temperature ≥37.6 ℃ since postoperative day 4,②no evidence of infection,③a time relationship between fever and the administration of causative drugs:a fever occurring with drug administration and disappearing after drug cessation within 3 days,④no other causes for the fever,⑤oral temperature ≤ 37.6 ℃ until leaving hospital.Exclusion criteria for DIH were listed below:①possible pathological fever,e.g.,in cancer,②hospitalization within 3 days,③no surgery,④severe trauma,for example,visceral or central nervous system injury.Results All causative drugs were for injection.By comparison,duration of antibacterial administration is significantly shorter in group Ⅱ than in group Ⅰ (1.7 ± 1.7 vs.4.6-± 1.8days,P ＜ 0.01),and total DIH incidence and antibacterials related DIH incidence were significantly lower in group Ⅱ than in group Ⅰ (7.3％ vs.30.1％,1.5％ vs.25.3％,both P ＜0.01).Conclusion DIH incidence is related with drug type especially with antibacterials overuse,and changed with drug program.DIH was more serious for injection of antibacterials than injection of traditional Chinese medicine.Decrease of antibacterials usage is positively associated with the decreased DIH incidence.Safe medication should begin from safe usage of antibacterials.

Objective To explore whether major depressive disorder（MDD）and the therapeutic effect of fluoxetine are related to a functional polymorphism-1019C/G in the promoter region of the 5-HT1A receptor（HTR1A）gene.Methods Genotype and allele frequencies of HTR1A receptor gene-1019C/G polymorphism in MDD patients and healthy subjects（control）were examined by PCR-RFLP technique.Before and after the MDD patients accepted fluoxetine treatment for 6 weeks,17-item Hamilton depression rating scales（HAMD）were made to determine the severity of the symptoms,the outcome and remission status.Results There were significant differences in-1019C/G gene genotypes and alleles distribution between the patients and the healthy control,G allele frequency of the MDD patient was higher than that of the healthy control（P 0.05）.There were significant differences in HAMD scores among the patients with different genotypes in MDD group（P 0.05）,the score of C/C genotype patient was especially higher than that of C/G genotype（P 0.05）and G/G genotype patient（P =0.008）.There was no statistical difference in the therapeutic effect of fluoxetine among the patients with different genotypes in MDD group（P =0.761）.Conclusion HTR1A gene-1019C/G genetic polymorphism might related to MDD,especially G allele might be the possible risk factor of MDD.C allele might be correlated with the degree of pathogenetic severity,especially patients with the-1019C/C carriers.-1019C/G genetic polymorphism was not related to the clinical outcome of MDD patients treated with fluoxetine.