Background: Epithelial ovarian cancer is recognized as a chronic disease with low diagnosis rate and high mortality. Despite significant improvement in the surgical care and the introduction of new and more efficacious chemotherapy combination, the majority of women diagnosed with advanced — stage cancer suffer from recurrence of their disease. Since therapy that can cure recurrent disease is essentially nonexistent, attempts at prolongation of overall disease—free survival become an alternative goal. Especially the effect of secondary cytoreductive surgery (SCR) is debatable.Objective: Use the systematic review and Meta—analysis to study the relative factors and to evaluate secondary surgery in the median survival time of recurrent epithelial ovarian cancer patients.Materials and Methods: A systematic review of clinical trials of secondary surgery of recurrent ovarian cancer was performed. Trials were identified by searching for Medline, Pubmed, Chinese Biological Medicine Database and Chinese EBM Database. The following outcomes were assessed: The number of patients accepting the secondary surgery and their median survival time. According to the different definitions of optimal SCR, the subgroups were designed as the macroscopic — free residual disease , the residual disease≤2cm , the residual disease≤1cm and the suboptimal SCR. Fisher's method was used to perform statistical

  Nepofam Hydrochloride is central analgesic without anaesthesia.It’s painful function is equal to morphine ,it’s addiction and side effect are all small.It also has the advantage of reliving pain.loosing muscle.reducing the heat.and the anti- melancholy function.It has no anaesthesia .no quiet function and does’t repress central nervous system.It can loose muscle and can agree with stomach .does’t stimulate and cause issue of blood,it can reunite an application with various medicine.Compare to opium,it has no dependence and tolerance,has no function towards breathing and circulatory system.  Now,in clinical,the method of relieving surgical pain is launched extensively,Nepofam Hydrochloride was injected in epidural pump.But the study at home or abroad,only report the orally and intravenous injection pharmacokinetics .Inquiry into the pharmacokinetics of nepofam contribute to our first step to comprehensively understand this medicine in body process and the rationality after neurocanal anesthesia.  On the base of characteristic ultraviolet absorption of nepofam hydrochloride ,the high performance liquid chromatography(HPLC) methods was established for analysis of nepofam.The linearity.specificity.repeatability and recovery met with the requirements of Chinese pharmacopoeia(edition 2000).  In the bioavailbility experiment, the nepofam concentration was analyzed by HPLC injected through eqidural anesthesia.Parameters were estimated by Winnolin pharmacodinetics software. The results showed that: The Nepofam Hydrochloride can be absorbed in plasma when it was acceped epidural anesthesia and the plasma concentration-time curves of Nepofam Hydrochliride was fitted to a one-compartment open modle.It’s dispersibility is so big that it can relieve pain fastly during epidural anesthesia.A HPLC is a stable,simple and sensitive method for determination of plasma Nefopam concentration during epidural anesthesia . the main pharmacokinetic parameters are Tpeak(1.3±0.13)h, t1/2(5.23±1.94)h, Cmax (253.86±14.43) ng/ml.

Objective To establish a rapid, specific and accurate method to identify and detect Yersinia pestis with Peptide Nucleic Acid (PNA) probes and streptavidin modified magnetic nanoparticles or Cy5-nanoparticles using fluorescence scan technology. Methods A pair of PNA probes were synthesized with Expedite 8909 nucleic acid synthesis system after being designed based on sequence of caf1 gene in plasmid pMT1 of Y. pestis, then they were biotinylated and conjugated onto streptavidin modified magnetic beads or Cy5-nanoparticles, respectively. After the hybridization between the probes and the target DNA, fluorescence scan technology was used to detect the DNA of Y. pestis. The optimal reaction conditions were definitely explored and sensitivity and specificity of the assay were evaluated. On the other hand, the performence between PNA probes and DNA probes, between magnetic nanoparticles provided by Hunan University and commercially available magnetic beads, as well as between Cy5-nanoparticles and single Cy5 molecule were investigated to validate which one has the advantages in nucleic acid hybridization field.Results The PNA probe-based method for detection of Yersinia pestis was established and optimized, the detection limit is 0.9μg/mL (target DNA). PNA probes, magnetic nanoparticles and Cy5-nanoparticles showed significant advantages over the similar products from the market.Conclusions PNA probes displayed excellent hybridization and highly specific recognization capability to target DNA due to their unique structure characteristics. Magnetic nanoparticles can separate the free nucleic acid or excessive probes from probes-target DNA complex easily and effectively, which improved the detection sensitivity. The stability for light and fluorescence signature magnification ability of Cy5-nanoparticles increased the detection sensitivity thousands of times compared

Human fibrinogen(Fg), namely coagulation factor I, is not only with the highest protein level in all plasma proteins, but the central protein of coagulation system. The final stage of the coagulation pathway is the formation of thrombin, in which the fibrinogen is transformed into fibrin. In addition to direct participation into coagulation procedure, fibrinogen can mediate the platelet aggregation, consequently has an influence on blood viscosity, and is the great risk factor of cardial-brain vascular diseases. The defects of fibrinogen gene can contribute to congenital afibrinogenemia(or hypofibrinogenemia), and dysfibrinogenemia.The fibrinogen locus comprises three genes coding for fibrinogen gamma (FGG), alpha (FGA), and beta (FGB), clustered in a region of ～50 kb on chromosome 4q28-q31. The gene defect of every one of three fibrinogen genes can lead to the abnormality of fibrinogen protein level or its function. Congenital afibrinogenemia (Mendelian Inheritance in Man No. 202400) was originally described in 1920, and to date about 150 families with this disorder have been described in the literatures. As is commonly the case with rare autosomal recessive disorders, ～50% of cases are associated with consanguinity.Objectives   (1)to study the phenotype, perform family survey and clinical diagnosis for one congenital afibrinogenemia patient and his family; (2)to perform fibrinogen genes sequence assay for one congenital afibrinogenemia patient and his family, then find the causative mutation and heredity regularity, finally do some primary researches

  Objective Compare hypothermic cold machine perfusion (CMP) preservation with Simple Cold Storage (SCS) to investigate the model and effect of hypothermic CMP preservation in liver transplantation.  Methods 35male Wistar rats were randomly divided into three groups. The livers were initially perfused without preservation in the normal group. The livers were perfused after being preserved for 12 , 24 and 36hours by Simple Cold Storage(SCS) in the control group. The livers were perfused after being preserved for 12 , 24 and 36 hours by CMP in the experiment group. The changes in tumor necrosis factor(TNF-a)content,hyaluronic acid(HA)uptake,alanine aminotransferase (ALT)activity and morphological changes in hepotocytes and sinusoidal endothelial cell (SEC) under light microscopy and electron microscopy were observed by using isolaec perfused rat liver (IPRL) model. The effect of SCS group compared with CMP preservation group.  Results Compared the control group and the experiment group with the normal group ,TNF-a content and ALT activity were increased remarkably (both P<0.05)and HA uptake was decreased evidently ( P<0.05). Along with the time of liver reperfusion going on , the values of ALT, TNF-a, were significantly lower in HMP group than in control group at the same time (p<0.05). The value of HA uptake was significantly higher in CMP group than in SCS group at the same time (p<0.05).Along with the time of preservation going on, the histopathologic changes gradually aggravated, the changes included degeneration and necrosis of liver cell, different degrees configuration destroy of hepatic sinusoid in the experiment group were milder than in the control group.  Conclusion These results suggest that CMP can lessen SEC injury and reperfusion injury as well as prolong preservation time effectively.

  Objective: To investigate the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer.;To study its expression of CD83 CD80 CD86 in dentritic cell .and investigate the immune states of sentinel lymph node and the mechanisms by which tumors escape immune recognition .  Methords: From December 2004 to December 2005,fourty-five patients with cervical cancer at stageⅠa(n=5)、Ⅰb1(n==24)、Ⅰb2(n==12)、Ⅱa(n==4) underwent SLN detection by using blue dye (patent blue violet 1%).Four ml of patent blue violet 1% was injected into the cervix at 4 points around the tumor just at the time radical hysterectomy and extensive biolateral pelvic lymphadenectomy.Tumor characteristics and specific locations of lymphatic dye uptake were recorded.The samples of SLN and non-SLN(NSLN) were compared with the expression of CD83 CD80 CD86 in dendritic cell.  Result: (1)Out of 45 patients ,SLNS were detected in 40 patients.A total of 86 SLNS were identified and the mean was 2 per patients.The detection rate of SLN was 89%.Six patients(13%) were diagnosed with lymph node metastase and all 6 patients are in the group SLN.One patient had both positive SLNS and pelvic lymph node.No one had positive pelvic lymph node and negative SLN,The predictive rate was 100% and the false -negative rate was zero.  (2)The expression rates of CD83、CD80、CD86 inmetastatic SLN were less than those in non-metastatic SLN and non-SLN. There was no significant difference in the rates of CD83、CD80、CD86 between non-metastatic SLN and non-SLN.  Conclusion: (1)SLN detection can successfully predict the pelvic lymph node status in patients with early cervical cancer..  (2) The metastatism of cervical cancer lymph node is related with the number of dendritic cell of CD83、CD80、CD86 decreases.  (3)Patients with early cervical cancer can be avoided with conventional pelvic lymph node excision.in the face of immunology.

  Objective:research systematically into the isolation,culture and direct differentiation to osteoblast of embryonic stem cells.  Method: To obtain feeder layer of primary mouse embryo fibroblasts(PMEF), 13.5d pregnant KM mouse was chosen as a donor. After using mitomycin-C treated PMEF, they were used as feeder cells in media of DMEM for isolation ES cell colonies and for coculture with ES-D3 cells. We flushed blastocysts from pregnant uterus at p.c. 4.After 4 to 5 days,nest-like clones of inner cell mass appeared and were dispersed by 0.25% trypsine-0.02

  Fibrinogen-dependent cross-linking of glycoprotein(GP)Ⅱb/Ⅲa on activated platelets is the final mechanism leading to platelet-dependent thrombus formation. The binding of fibrino- gen toⅡb/Ⅲa is mediated by the Arg-Gly-Asp (RGD) recognition sequence. As platelet GPⅡb/Ⅲa receptor antagonist, synthetic peptides based RGD have been proved to be an effective antiplatelet drug. Based on the RGD sequence, we designed a kind of linear peptide: H2N(CH2)7-CO-Gly-Asp-Trp (A0GDW). In the preclinical study, the preparation technology and quality control method of A0GDW were set up. On the basis of all the work, the antithrombotic effective and safety of A0GDW were evaluated.  A0GDW were synthesized by Fmoc-SPPS method. To synthesized A0GDW, the strategies are as followings: Fmoc-group as protective group forα-NH2;TBTU,DIEA and HOBt as coupling reagent; And ethanedithiol-phenol-thioanisole- H2O-TFA(2.5:5:5:5:82.5,V/V) as cleav- ing solution. The structure of A0GDW was identified to be correct by ESI-MS analysis. The separation and purification of A0GDW was carried out with reversed-phase liquid chromato- graphy(RPLC). The purity of A0GDW was 98.3%.  A specific HPLC method with high sensitivity was established which has desirable separation results. The appearance, melting point, the stability and changes of the materials and content are also discussed.  We used turbidmetric method to measure platelet aggregation. A0GDW remarkably inhibit- ed rabbit platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA) or collagen (COLL) in vitro. A0GDW at 0.4mg/kg iv inhibited platelet aggregation induced by ADP in rabbits, taking effect immediately after A0GDW intravenous injection and lasting for 100min. To study the antithrombosis effect of A0GDW, we established two kinds of animal models. On the rabbit model of artery-vein bypass thrombus formation, A0GDW can abate the wet weight of thrombus in vivo. The result also showed that there were dose-dependent increases in inhibiting rate of the wet weight. On the model of rat carotid thrombosis induced by 20% FeCl3, A0GDW was intravenously infused for prevention before thrombosis. It was found that the thrombosis was significantly suppressed. The tail artery bleeding time was determined in mice through tail venous injection. As a presumed consequence of the inhibition of platelet function, A0GDW remarkably lengthened the bleeding time. But the bleeding time of A0GDW is much shorter than the same dosage of Tirofiban (the positive control). In addition, we testified the effect of A0GDW on

The caspase (cysteinyl-aspartate protease) family represents a class ofintracellular proteases playing a critical role in apoptotic cell death pathwaysand activation of pro-inflammatory cytokines. Their enzymatic properties aregoverned by a nearly absolute specificity for substrates containing asparticacid at the P1 site and by the use of a cysteine side-chain for peptide-bondhydrolysis. To date, 14 human caspases have been identified. Since activationof caspase-dependent apoptotic cell death has been implicated in the etiologyof many harmful human disorders, such as immunodeficiency, Alzheimer′s,Parkinson′s, and Huntington′s diseases, as well as ischemia, brain trauma, andamyotrophic lateral sclerosis, inhibitor of caspase is believed to be a valuabletherapeutic approach.There are now many designed potent and selective protease inhibitors.Although caspase inhibitors display a diverse range of biological properties,To be effective and practical drugs, they still have some deficiencies to beovercome, such as instability, low bioavailability and poor pharmacologicalprofiles. Therefore to be effective drugs, protease inhibitors need to haveminimal peptide characters, high stability to nonselective proteolyticdegradation, good membrane permeability, long lifetimes in the bloodstreamand in cells, low susceptibility to elimination, high selectivity for a protease,and good bioavailability (preferably by oral delivery).For many years intense work has been focused on the synthesis of peptideanalogues in the search for mimics with enhanced activity and biologicalhalf-lives. Examples of modifications introduced in peptides are the placementof L-amino acid residues by D-amino acids (retro-inverso transformation) orby unnatural residues (e.g., sarcosine and β-alanine) and the modification ofpeptide bonds. These changes provide pseudopeptides or peptidomimeticswith a higher metabolic stability, since most natural proteases cannot cleaveD-amino acid residues and nonpeptide bonds. At present, the retro-inversotransformation remains an important pseudopeptidic modification undertakenby numberous bioorganic chemists. Many partially modification retro-inverso(PMRI) analogs of peptides were synthesized and tested. It was reported thatreversed peptide not only displayed stability toward enzymatic degradation butalso improved bioavailability and potency. The remarkable resistance of PMRIanalogs to proteolytic degradation combined with retention of high biologicalactivity following oral or intravenous administration provides a strong impetusfor the continuing efforts on this modification.In this paper, we designed the novel PMRI caspase-3 inhibitors based on theinhibitor Z-VAD-CHO. We replaced L-amino acid with D-amino acid, whichresulted in all the amide bonds reversed. However, C-terminal P1 siteremained. Our synthesis progress consisted of three major parts, C-terminal P1site synthesis, coupling and deprotection of the inhibitor and completion of theinhibitor. Among them, C-terminal compound synthesis is the key part. Part1: In the first step of our experiment ,succinic anhydride reacted with benzylalcohol to give monobenzyl succinate. Second, the product was treated withLithium bis(trimethyl-silyl) amide in dry tetrahydrofurane. The ethyl formatewas added to afford the α-formyl α-benzyl succinate . Then, the aldehyde andcarboxyl groups were protected by reacting with the trimethyl orthoformate inthe presence of p-toluene sulfonic acid as the catalyst to provide. Part 2: thebenzyl group was removed by catalytic hydrogenation using 5% Pd/c. Peptidealdehyde derivatives were formed by using the BOP method. Part 3 : Finally,we removed the protective group of aldehyde using 5% aqueous trifluoroaceticacid. In order to stabilize aldehyde group, we transformed them into itsbisulfite adduct by adding saturated solution of sodium bisulfite. Now, wehave already successfully synthesized the analogues of Z-VAD-CHO andevery product have been purified and characterized by 1~H NMR or MS.The analogues have been tested for their ability to inhibit caspase-3catalyzed proteolytic breakdown of its fluorogenic substrate, DEVD-AFC. Inour experiment, we made use of the product of Biovision company, Caspase-3Inhibitor Drug Screening Kit. We have demonstrated inhibitory activity ( IC50 )of analogues are 71μM and 43μM,according to the method provided by kit.Parallel experiments demonstrated that the IC50 value for Z-VAD-FMK, apotent tripeptide inhibitor of caspase-3 was equal to 1.7μM under the sameexperimental conditions.In summary, we have developed a general procedure for preparation ofretro-inverso peptidyl aldehydes, and synthesized PMRI caspase-3 inhibitorwhich has never been reported before using the new method. Bioassays showsthe inhibitor has moderate activity compared with that of the inhibitorsreported previously. This is only our primary work, and the result isencouraging, suggesting that caspase-3 inhibitors built on this novel scaffoldhave the potential for future drug development.

Obejective: To investigate the imaging,pathological,hematocytic, and immunological changes pre- and post swine splenic arterial embolization, using a coaxial microcatheter technique under a balloon catheter occluded the trunck of the splenic artery. To evaluate the potential utility of the new method for management of megalosplenia-hypersplenism.Methods: Seven swines were divided into the experiment and control group.Two swines as the control were treated with the routine method, using the PVA particle and gelfoams for the transcatheter embolization of the splenic artery. Five swines as the experimental group were treated with a new method, using a coaxial microcatheter technique under a balloon catheter occluded the trunck of the splenic artery. An emulsion of N-butyl 2-cyanoacrylate and iodized oil was used for the selective embolization of the splenic artery in the experiment group. The general reaction of the animals, the imaging,pathological, hematological,and immunological changes were observed.Statistics. Measurement data were espressed as means±SD and analyzed by t Test with a STATA7.0 software.Results: (1)In the experiment group ,the first pig showed the symptoms ofvomiting, anorexia and fantod, but these symptoms disappeared in the folbwing day. The third one showed the same symptomsa as the first one but more severely, and died of necrotizing pancreatitis confirmed by pathology in the second dayafter the procedure. The other three appeared normal in the general condition after the treatment. In the control,two swines showed anorexia ,fantod , weak breath for 2 days after the procedure.(2)In the experiment group, selective splenic arterial angiography showed that the contrast medium was slowed dowm in the splenic artery obviously and stagnated in the spleen, and CT plain scan showed decreased in the size of the spleen after 30 minutes under the balloon occlusion of the splenic artery(35~38°/o, p0.05).c) Immunologic changes. There were no significant differences on the immunological test (IgG> IgM> IgA)in the living pigs pre and post the embolization (P>0.05).Conclusions:a) Transcatheter selective splenic arterial embolization using an emulsion of N-butyl 2-cyanoacrylate and iodized oil, under a balloon catheter occluded the trunck of the splenic artery, is an effective new method for treatment of megalosplenia and hypersplenism.b) In comparison with the conventional transcatheter splenic arterial embolization technique, the new method had a less reaction after the embolization.c) Using the new method, recanalization and establishment of collateral branchescould be prevented after embolization of the spleen.