Objective To investigate the efficacy of nedaplati docetaxel combined with radiotherapy on patients with locally advanced cervical cancer.Methods The clinical data of 99 cases with pathologically diagnosed advanced cervical cancer from Jun.2013 to jul.2014 in the Matemal and Child Health Care Hospital of Tangshan were recorded.The patients were randomly divided into the control group (45 cases only with radiotherapy) and the observation group(54 cases with nedaplati and docetaxel beside radiotherapy).Results The effective rate in observation group was 90.74％,higher than control group (71.11％,x2 =6.358,P =0.017).There were significant incidence of bone marrow suppression renal dysfunction and gastrointestinal both in two groups,but can endure.There was no significant difference in term of side effect in two groups (P ＞0.05).Conclusion The therapy of nedaplati and docetaxel combined with radiotherapy has better effect for patients with advanced cervical cancer and without significantly increasing side effect.

Aims To establish several behavioral paradigms to characterize the psychotropic effects of hallucinogens which ze-brafish was utilized as a model animal, and then to investigate the effects of potent hallucinogenic drugs on these models. Methods With the video record and track system, the behavior was recorded and quantified automatically. In the experiments, the bottom dwelling test, social behavior and mirror test were performed to test the hallucinogenic effects of drugs. Metham-phetamine (METH, 2 mg·L-1) and ketamine (20 mg·L-1) were selected as experimental challenges. The 30 min pre-treat-ment time was chosen based on our prior experience in zebrafish models. Results Compared to the normal group, in dwelling test, acute exposure of zebrafish to METH and ketamine de-creased transitions significantly, and in mirror reflection test, the drug-treated fish changed the preference for mirror zone, and ex-hibited aggressive for their mirror images. The pretreatment of METH and ketamine significantly reduced the contact durations, and the ketamine inhibited the contact frequency each other, the results indicated that the social interaction of zebrafish was im-paired. Conclusion The results confirm high sensitivity of ze-brafish models to hallucinogenic compounds with complex behav-ioral and physiological effects.

The C-terminal tail of opioid receptor is important for opioid receptor phosphorylation,desensitization and internalization after opioid agonists treatment.The C-terminal point mutant and truncated mutant of amino acid residues of ?opioid receptors such as T394A,T383A,T357A,S355A affect the function of the opioid receptor obviously.The identical results could be seen in the C-terminal point mutant S363A of ?opioid receptor and S369A of ?opioid receptor.It is well known that opioid receptor requires interaction with other proteins for function,regulation and trafficking.Although proteins such as PPL,FilaminA,PLD2,PKCI,GASP and EBP50/NHERF have been identified to interact with C-terminals of opioid receptors,the role of interaction of these proteins with opioid receptor in the dependence,tolerance and addiction of opioids is dubious.Therefore,looking for the proteins specifically interacting with the C-terminals of opioid receptor may be important to understand the mechanism of opioids addiction.

Objective To investigate rats reared in social isolation as a model of behavioral symptoms of neurodevelop-mental psychiatric disorders including schizophrenia.Methods Male rat pups were housed in individual cages from post-weaning to adulthood.Locomotor activity detection, Morris water maze test and social interaction test were performed. Results Compared with controls, the social isolation-reared rats got more body mass, showed locomotor hyperactivity and increased social interaction, but significant spatial learning changes were not observed in Morris water maze test.Conclu-sion Exposing rats to social isolation can profoundly affect behavior in adulthood, which can be used to build animal mod-els of neurodevelopmental psychiatric disorders including schizophrenia.

Cardiac hypertrophy is a major adaptational mechanism in stresses such as pressure overload and neurohumoral stimulation.As powerful vasoconstrictor peptides in cardiovascular system,especially the vascular endothelium,smooth muscle cells and cardiocyte,ETs play important physiological roles in the regulation of normal cardiovascular function.Excessive generation of ETs in local cardiac muscle has been linked to myocardial hypertrophy.Endothelin-1(ET-1) in cardiac muscle exerts its actions in the development of myocardial hypertrophy through binding to specific receptors and interacting with other vasoactive substance of local tissues.ET-1 can induce the hypertrophy for cardiocytes and the proliferation for cardiac fibroblasts by ETA.ETB receptors are implicated both in initiating and maintaining myocardial hypertrophy.As a new target of drug,ET receptors have become the research focus,and great progress has been made on the development of the ET antagonists.

Two types of cannabinoid receptors,named cannabinoid receptor 1(CB1) and cannabinoid receptor 2(CB2),have been cloned.CB2 receptors are expressed predominantly in the peripheral immune tissues,but accumulating evidence has revealed that CB2 receptors are also expressed in CNS.Previous studies showed that CB2 agonists can cure and suppress formation of inflammatory and neurophathic pain without central effects after chronic administration.Therefore,they will have good clinical applications in the treatment of pain and neurodegenerative diseases.In this paper,we will review the tissue distribution of CB2 in CNS and pharmacological characteristics of the CB2 agonists have been reviewed.

The homeostasis of extracellular glutamate concentration is critically regulated by glutamate transporters(GTs).Malfunction or decreased expression of GTs has been implicated in the pathogenesis of various nervous system diseases.And among the GTs,glutamate transporter 1(GLT-1)plays a critical role as "glutamate pump".Recent research also finds some GLT-1 variants which alternate C-terminal splicings.Altered expression of proteins encoded by splice variants of GLT-1 has been noted in a number of disease states.Maintaining a physiological range of extracellular glutamate through regulating GTs expression or function may improve some pathological conditions.Many drugs are reported that can regulate GTs.For example,ceftriaxone,phencyclidine,citicoline,riluzole,AKT,thrombosin can up-regulate the expression or function of glutamate transporters;etomidate,clozapine,aspartic acid analogs,endothelin can down-regulate the expression or function of glutamate transporters.In this paper,the drugs which effect GTs will be summarized in order to provide a new insight into the drug design and clinical treatment of neurological diseases.

Human rhinoviruses (HRVs) are the causative pathogens in more than half of viral upper respiratory tract infections. Currently, no antiviral agents that are active against HRVs are available for clinical use. Because only higher primates are susceptible to HRVs, the screening of new drug is most commonly based on the cell line model. In this study, isolated rabbit airway smooth muscles (ASM) tissue model has been established, and the airway responsiveness with different treatment has been examined. Relative to control tissues, the maximal constrictor (Tmax) response to ACh increased significantly 150% in ASM inoculated with HRV, and relaxation to isoproterenol has been attenuated to 63%. And the abnormal responsiveness can be inhibited in presence of pretreatment with several new compounds which have been exhibited effective anti-HRV activity on cell lines. The results demonstrate that the established ASM model will be applied to screening the anti-HRVs drugs.

Schizophrenia, described as the worst disease affecting mankind, is a severe and disabling mental disorder. Schizophrenia is characterized by complicated symptoms and still lacks a diagnostic neuropathology, so developing schizophrenia animal models which have quantifiable measures tested in a similar fashion in both humans and animals will play a key role in new therapeutic approaches. According to the symptoms of cognitive impairment and emotional disorder, the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 was applied to induce schizophrenia-like behavior in mice. Locomotor activity and prepulse inhibition (PPI) were selected as indices and the effect of clozapine was also investigated in this model. The results showed that compared with the normal group, MK-801-treated mice exhibited significantly increased locomotor activity and impaired PPI, and pre-exposure to clozapine could ameliorate the abnormality and make it back to normal level. These findings suggest that the model we established could be a useful tool for antipsychotic drug screening.

This study investigates whether kappa-opioid receptor and ORL1 receptor may interact to form a heterodimer. In immunofluorescence and co-immunoprecipitation experiments, differentially epitope-tagged receptors, colocalization and heterodimerization of kappa-opioid receptor and ORL1 receptor were used and examined in primary culturing rat neurons, Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. The results show that fluorescence of both kappa-opioid receptor and ORL1 receptor were overlapping in primary culturing hippocampal and cortical neurons. Similarly in co-expressing CHO or HEK293 cells, HA-KOR and Myc-ORL1 were almost exclusively confined to the membranes, revealing extensive colocalization. When Flag-KOR and Myc-ORL1 were co-expressing in CHO cells, heterodimerization was identified to have the ability to co-immunoprecipitate ORL1-receptors with kappa-opioid receptor and vice versa. In the current study, further evidence was provided for the direct interaction of two subtypes of opioid receptors, kappa-opioid receptor and ORL1-receptor, to form the heterodimerization. The finding represents the novel pharmacological mechanism for modulation of opioid receptor function as well as diversity of G protein-coupled receptors.