Aim To establish the pharmacokinetic-pharmacodynamic(PK-PD) modeling to characterize the antipyretic effects of coptisine, an active component in coptis chinensis on rats.Methods Nine healthy male Sprague-Dawley(SD) rats were randomly divided into three groups, each with three.The rats in the first group were injected intravenously with lipopolysaccharide(LPS,100 μg·kg-1) alone.The second and third group rats were given coptisine high-dose(3.87 mg·kg-1) and coptisine low-dose(1.93 mg·kg-1) by tail vein injection at 30 min after LPS injection, respectively.Body temperature was measured at different time points, and blood samples from tail vein were collected simultaneously.The blood concentration of coptisine was determined by ultra performance liquid chromatography.Monolix software was used to model PK-PD of coptisine mean plasma concentration and temperature effects,by population computation with non-covariates.Besides.the model with advantage was selected by the fitting goodness.Results Coptisine could inhibit body temperature of endotoxin-induced fever in rats significantly.Two-compartment linear elimination model was used to describe the final PK model.Gaussian function, an input function of body temperature changes, which was used to depict PD model, the PK and PD models were connected by the Emax model.At last, the final model was fitted better;the fitting results indicated that the EC50 of antipyretic effect of coptisine was 89.7 μg·L-1, and the Emax was 1.88℃.Conclusions Coptisine has a powerful anti-pyretic effect on endotoxin-induced pyrexia of rats with high potency, Low in vivo distribution and quick clearance.

Objective:To discuss the clinical characteristics,diagnosis and treatment experience of a case of lateral ectopic thyroid.Methods:The patient with lateral ectopic thyroid was diagnosed by thyroid color ultrasound and single-photon emission computed tomography(SPECT)-CT examination.The right thyroidectomy and the thyroid tissue in cervical section Ⅳ of the patient were removed by received the operation.The pathological examination after operation was performed.The daily usage of euthyrox after operation was 50 μg.Results:The patient recovered well,who accepted 10 months follow-up with normal life and stable condition,and had no recurrence and metastasis.Conclusion:The mechanism of lateral ectopic thyroidy is not clear yet,the surgical treatment can result in good effectiveness and better prognosis.

Objective • To perform the pharmacokinetic (PK) studies of DDDA3, a dual inhibitor of both acetylcholinesterase and butyrylcholinesterase, in order to provide experimental evidence for the evaluation of in vivo activity against Alzheimer's disease (AD) and the formulation optimization. Methods • A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of DDDA3 was developed and validated. This method was applied to pharmacokinetic studies of DDDA3 in rat plasma. Protein precipitation approach was used to prepare plasma samples. To lower the detection limit, the concentration step was utilized. The samples were analyzed on a Zorbax SB-Aq column (2.1 mm×100 mm, 3.5 μm) with the mobile phase composed of methanol and water (75:25 by volume, containing 0.1% formic acid and 10 mmol/L ammonium formate) and determined by positive electrospray ionization in multiple reaction monitoring mode. Results • The lower limit of quantification was 0.5 ng/mL and the linear range was 0.5-500 ng/mL. The absolute oral bioavailability of DDDA3 in SD rats was 78.4%. Conclusion • DDDA3 has high potentials as anti-AD agents, with good oral bioavailability, fast absorption rate, and long-lasting blood concentration; however, the formulation should be optimized to improve the solubility.

Objective • To establish a method for identifying the chimeric rates in Down syndrome chimeric mice, and study the chimeric rules in different organs. Methods • The proportion of trisomic cells (Tc1 cells) in different organs was calculated by detecting the relative quantity of human chromosome 21 (Hsa21) and mouse chromosome 15 (Mmu15) in samples. The relative quantity of Hsa21 and Mmu15 was evaluated with specific primers for genes SIM2 on Hsa21 and Derl1 on Mmu15, respectively, by quantitative real time PCR (qPCR) technology. Results • Three mice were chimeras and the chimeric levels of Tc1 cells were different in various tissues. The chimeric rates in hearts of these 3 mice were 8.98%, 21.71% and 57.70%; in cerebellums, the chimeric rates were 5.62%, 20.17% and 40.43%; in brains, the rates were 8.48%, 15.35% and 20.45%; in livers, the rates were 2.66%, 6.50% and 16.84%; and in spleens, the rates were 1.73%, 3.80% and 11.80%. Conclusion • The chimeric rate of trisomic cells in Down syndrome chimeric mice can be detected by qPCR technology by using primers for genes on specific chromosomes. The chimerism occurs in the hearts, cerebellums, brains, livers and spleens of the chimeric mice and the chimeric rate of Tc1 cells tends to be the highest in the hearts.

Platinum compounds are crucial chemotherapy drugs for children with solid tumor, and the ototoxicity is one of the dose-limiting toxicities. Platinum-induced hearing loss is detrimental to language learning and social development especially for children. Several clinical trials of drugs against platinum-based ototoxicity have been carried out, the results prompted that sodium thiosulfate, amifostine and N-acetylcysteine potentially reduce the occurrence risk of hearing loss. Without affecting the therapeutic effect, preventive use of antagonists on platinum-based ototoxicity will improve the life quality and treatment compliance of pediatric patients with tumor.

OBJECTIVETo find a kind of quick and effective haemostasis to decrease the mortality of severe bleeding.

METHODS18 severe bleeding patients with different cause received recombinant activated factor VIIa (rFVIIa) were analyzed retrospectively.

RESULTSOf total 18 cases with severe bleeding, 13 cases cured, 3 cases were effective, 2 cases ineffective. The total clinical effective rate is 88.89%. After using rFVIIa, the PT, APTT and fibrinogen level of 6 DIC patients returned to normal within 12 hours; 13 patients whose the amount of bleeding can be evaluated stopped bleeding quickly. The fastest onset time was 10 min.

CONCLUSIONrFVIIa can stanch severe bleeding for a variety of reasons rapidly and effectively, including coagulopathy, thrombocytopenia, and obstetric hemorrhage. Application of rFVIIa may decrease mortality, when conventional treatment is not valid.

Adult ; Aged ; Aged, 80 and over ; Blood Coagulation Disorders ; drug therapy ; Factor VIIa ; therapeutic use ; Female ; Hemorrhage ; drug therapy ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

PURPOSE: Near-infrared fluorescence imaging with indocyanine green (ICG) has the potential to improve sentinel lymph node (SLN) mapping in breast cancer. In this clinical trial, we compared the potential value of ICG combined with blue dye with that of blue dye alone for detecting SLNs. METHODS: Patients undergoing SLN biopsy (SLNB) between November 2010 and November 2013 were included. Up to December 2011, SLNs were detected by using patent blue (PB) alone, and since January 2012, by using PB in combination with ICG. The patients were divided into the following two groups: group A (ICG-PB; n=96) and group B (PB; n=73), and SLN detection parameters were compared between the groups. All patients underwent level I and II axillary dissections after SLNB. RESULTS: In group A, the SLN detection rate was 96.9% (93/96), the accuracy of detection was 98.9% (92/93), and the false-negative rate (FNR) was 3.4% (1/29). In group B, the SLN detection rate was 84.9% (62/73), the accuracy of detection was 96.8% (60/62), and the FNR was 11.1% (2/18). The ICG-PB group showed significantly superior results compared to the PB group for SLN detection (p=0.005) and a greatly improved FNR. CONCLUSION: The combined fluorescence and blue dye-based tracer technique was superior to the use of blue dye alone for identifying SLNs, and for predicting axillary lymph node status in patients with breast cancer; in addition, the combined technique had reduced false-negative results.
Biopsy ; Breast Neoplasms* ; Fluorescence ; Humans ; Indocyanine Green ; Lymph Nodes ; Optical Imaging* ; Sentinel Lymph Node Biopsy*

ObjectiveTo study the effect of enriched rehabilitative training on the functional recovery and neuronal dentritic growth following cerebral ischemia/reperfusion.Methods32 male Wistar rats,weighting 180～200 g,were randomly divided into a ischemic group(n=16) and a sham-operation group(n=16) after beforehand trainings.Rats were subjected to 2 h of right middle cerebral artery occlusion before reperfusion.After surgery,the ischemic group were randomly divided into a ischemia + enrichment(IE) group and a ischemia + standard housing(IS) group;the sham-operation group were randomly divided into a sham + enrichment(SE) group and a sham + standard housing(SS) group.After 24 h reperfusion,IE and SE groups were housed in enriched cages,and given enriched rehabilitative training according to the scheme.At the same time,IS and SS groups were housed in standard cages without any training.The functions of 4 groups were evaluated at 24 h,1 week,2 weeks,3 weeks and 4 week after operation.Dentritic growth of layer V pyramidal cells of the undamaged forelimb motor cortex was examined using Golgi-Cox procedure.ResultsIE group showed better function than IS group in all behavioral test.There was no significant difference in limb-placement test at 3 weeks(P>0.05) and in footfault test at 4 weeks(P>0.05) after operation between IE and SE group.The mean of basilar dentrite branching points in IE group was significantly greater than that of other groups(P<0.01).ConclusionEnriched rehabilitative training can promote functional recovery and enhance neural plasticity after cerebral ischemia/ reperfusion in rats.

To clone the 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (TwMCT) full length cDNA from Tripterygium wilfordii, the specific primers were designed according to the transcriptome data and the LCPCR were carried out. After a series of bioinformatics analysis on the TwMCT, the MeJA induced expression content were investigated by real-time fluorescence quantification polymerase chain reaction (RT-qPCR). The result showed that the full of TwMCTcDNA was 1 318 bp nucleotides encoding 311 amino acids. The molecular weight of the deduced TwMCT protein was about 34.14 kDa and the theoretical isoelectric point was 8.65. Result of the RT-qPCR analysis indicated that the content of TwMCT mRNA expression in T. wilfordii suspension cell was rising after treating with MeJA and reached the maximum in 24 h. Cloning and analyzing TwMCT gene from T. wilfordii provided gene element for studying the function and expression regulation of secondary metabolites.
Amino Acid Sequence ; Cloning, Molecular ; Erythritol ; analogs & derivatives ; metabolism ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Nucleotidyltransferases ; chemistry ; genetics ; metabolism ; Phylogeny ; Plant Proteins ; chemistry ; genetics ; metabolism ; Protein Structure, Secondary ; Sequence Alignment ; Sugar Phosphates ; metabolism ; Tripterygium ; chemistry ; enzymology ; genetics

OBJECTIVETo explore the method of fabricating larynx-shape tissue engineered cartilage by means of filling together with wrapping with pedicle myofascial flap.

METHODSSerial steps of solution casting, extrusion molding and particulate leaching were used to make larynx-shape [poly (3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHH] biomaterial models. The chondrocytes were seeded onto PHBHH models to form cell-PHBHH composites for culture in vitro for one week and then to fill and wrap larynx-shape composites with pedicle myofascial flap. After that to implant larynx-shape composites in situ on the back of adult New Zealand white rabbits (experimental groups n = 9). Control groups (n = 3) were the same measure as experimental groups but without chondrocytes on PHBHH models. Finally, morphological observation, HE & special staining and immunohistochemical test were conducted to evaluate the cartilage regeneration and its shape at 6, 8 and 12 weeks following implantation.

RESULTSThe PHBHH models appeared to be hollow half-trumpet with edges and corners of larynx-shape and its porosity > 90%. Pedicle myofascial flap using fascia as lining presented rich blood supply and had enough to fill and wrap larynx-shape composites. Tissue engineered larynx-shape cartilage specimens could be harvested at different period. It was demonstrated that the cartilaginous tissue formed in 6 weeks after implantation through histological and immunohistochemical examination and further maturity in 12 weeks and 18 weeks. But no cartilaginous tissue showed without chondrocytes on PHBHH as control groups to implant at the same time.

CONCLUSIONIt seems that pedicled myofascial flap showed sufficient blood supply and that the filling together with wrapping method with pedicled myofascial flap is appropriate for fabricating larynx-shape tissue engineered cartilage.

3-Hydroxybutyric Acid ; Animals ; Cartilage ; Cell Culture Techniques ; Fascia ; transplantation ; Larynx, Artificial ; Rabbits ; Surgical Flaps ; Tissue Engineering ; methods ; Tissue Scaffolds