Hypoxia refers to the reduction in tissue oxygen supply or utilization. It occurs in various pathological symptoms like embolism,anthracemia,and chronic obstructive sleep. At high altitude, lower partial pressure of oxygen compromises the supply of adequate oxygen to the tissues and leads to many clinical syndromes,such as acute mountain sickness,high-altitude cerebral edema,and high-altitude pulmonary edema. Histamine H3 receptor, primarily as a presynaptic receptor, is widely expressed in the central and peripheral systems. Histamine,dopamine,acetylcholine and many other neurotransmitters are regulated by histamine H3 receptor. Studies have shown that histamine H3 receptor is involved in the hypoxic response of the respiratory network. In addition,histamine,espe?cially histamine H3 receptor,participates in the regulation of cerebral ischemia in the central nervous system. In this paper,we reviewed the structure and functions of histamine H3 receptor and explained its role in the regulation of hypoxia so as to evaluate the possibility of histamine H3 receptor as a drug target for the therapy of hypoxia-induced injuries.

OBJECTIVE To investigate the protective effect of sGC003,a novel agonist of soluble guanylate cyclase,on endothelin-1(ET-1)-induced cardiomyocyte hypertrophy. METHODS Cardiomy?ocytes were isolated from neonatal Sprague-Dawley rats using serial enzymatic digestion and then incubated with ET-1 10 nmol·L-1 in the absence or presence of sGC003 0.01,0.1 and 1.0μmol·L-1. Hyper?trophic responses including the cardiomyocyte area(Image-Pro Plus 6.0),the expression of atrial natri?uretic peptide gene(ANP)mRNA(RT-PCR method)and total protein content(BCA method)were detect?ed. RESULTS After 48 h stimulation with ET-1 10 nmol·L-1,the cardiomyocyte area increased by 80%(P<0.01),the total protein content increased by 120%(P<0.01) and the expression of ANP mRNA up-regulated by 140%(P<0.01). sGC003 0.01,0.1 and 1.0μmol · L-1 elicited antihypertrophic actions, including inhibition of ET-1-mediated increase in the cardiomyocyte area(P<0.01),raised total protein content(P<0.05)and upregulation of ANP mRNA(P<0.05). CONCLUSION sGC003 has protective,car?diomyocyte-selective antihypertrophic effects in vitro.

Objective Ti investigate the applicatiin effect if clinical nursing pathway in cardiac valve replacement.Methods 60 patients with cardiac valve replacement were randimly divided inti experimental griup and cintril griup,with 30 patients in each griup.Clinical nursing pathway was applied thriugh periiperative nursing in the experimental griup,riutine nursing was applied in the cintril griup.Pistiperative hemirrhage,infectiin,pressure ulcer,keratitis,inci-dence if hypithermia cimplicatiin and satisfactiin were cimpared between the twi griups.Results Thriugh the applicatiin if clinical nursing pathway,the incidence if pistiperative cimplicatiins decreased significantly (P <0.05),pistiperative satisfactiin imprived ibviiusly (P <0.01). Conclusion Clinical nursing pathway can imprive nursing quality,reduce cimplicatiins and in-crease patients’satisfactiin,si it is wirthy if clinical applicatiin.

Objective Ti investigate the applicatiin effect if clinical nursing pathway in cardiac valve replacement.Methods 60 patients with cardiac valve replacement were randimly divided inti experimental griup and cintril griup,with 30 patients in each griup.Clinical nursing pathway was applied thriugh periiperative nursing in the experimental griup,riutine nursing was applied in the cintril griup.Pistiperative hemirrhage,infectiin,pressure ulcer,keratitis,inci-dence if hypithermia cimplicatiin and satisfactiin were cimpared between the twi griups.Results Thriugh the applicatiin if clinical nursing pathway,the incidence if pistiperative cimplicatiins decreased significantly (P <0.05),pistiperative satisfactiin imprived ibviiusly (P <0.01). Conclusion Clinical nursing pathway can imprive nursing quality,reduce cimplicatiins and in-crease patients’satisfactiin,si it is wirthy if clinical applicatiin.

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.

Aim To evaluate the antinociception of ω-SO3,a novel Omega-superfamily conotoxin,in rat formalin test.Methods Potency and duration of ω-SO3 antinociception compared with morphine were investigated in rat formalin test after acute intrathecal administration.Development of tolerance or cross tolerance to analgesia of ω-SO3 and morphine was tested in formalin test after chronic intrathecal administration.Locomotor activity of rat after acute intrathecal administration was tested to evaluate possible central side effects.Results In rat formalin test after intrathecal bolus injection,ω-SO3 produced dose-and time-dependent antinociception by suppressing acute(ED_(50),1.79 ng·g~(-1))and tonic phases(ED_(50),0.41 ng·g~(-1)),which was approximately 10-fold potency and twice longer-acting of morphine in blocking tonic phase responses.After repeated intrathecal injections twice daily for 5 consecutive days,ω-SO3 produced analgesia without loss of potency whereas morphine produced analgesia tolerance in rat formalin test;further,ω-SO3 still produced potent analgesia in morphine-tolerant rats.No changes in motor function were seen in rats receiving above antinociceptive doses.Conclusion sNovel ω-SO3 produces potent and long-acting spinal antinociception without observable motor dysfunction and after chronic intrathecal administration.ω-SO3 produces neither tolerance nor cross-tolerance to morphine analgesia.

Objective To explore the difference of resting-state default-mode network functional connectivity in patients with treatment-resistant depression (TRD) and in healthy subjects. Methods Ten patients with TRD and 12 healthy control subjects underwent 440 s fMRI scans while resting quietly. Functional connectivity analysis was used to isolate the default mode network in each subject. Group maps of the default-mode network were generated and compared between the two groups. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on network functional connectivity. Results Functional connectivity of both side of middle temporal gyrus, rectal gyrus, precuneus gray matter, left orbital gyrus, right inferior parietal lobule, and post cingulate gyrus in TRD group weakened compared with that of the control subjects. Conclusion There are resting default network connection weakening in multiple brain areas in TRD patients, which may lead to self-control and emotional behavior abnormal in patients.

Aim To investigate the effect of matrine on cytoskeletonof K562 cells. Methods Micropipette aspiration technique was adoptedto investigate the viscoelasticity of K562 cells, while the different ex-pression of cytoskeletal protein gene was analyzed by DNA microar-ray. Results In matrine-treated K562 cells, the viscoelastic propertiesKI, K2 and were decreased significantly from 726 ± 215 to 432 ±67,433 ±119 to 242±31, 72±38 to 50±15 respectively, and the geneexpression of prefoldin and ezrin was much stronger than that of controlcells. Conclusion The strueture and function can be changed in ma-trine-treated K562 cells.

AIM To evaluate bioavailability, biocompa- tibility and biodegradability of an injectable microsphere sustained release preparation of naltrexone(NTX) in 4 dogs. METHODS Pharmacokinetic data of NTX and remained NTX in microspheres in injection site were studied using high performance liquid chromatography(HPLC)-electrochemical detection with naloxone(NLX) as internal standard. Biocompatibility of the microspheres was assayed by histological examination. RESULTSPharmacokinetics of NTX after an intramuscular dose of 0.5 or 1.0 mg*kg-1 NTX indicated a plasma clearance range of 0.66 to 0.73 L*min-1 and a t1/2β range of 60.0 to 67.2 min. After a 1-week washout period without medication, NTX microspheres injection period about 4 weeks followed. After injection of 1.0 g of microspheres containing (296.5±2.1)mg of NTX, mean blood concentrations of NTX exceeded 1 μg*L-1 for 26-28 d, and cmax per dose (mg*kg-1) was only 1% of that after NTX dosing. It was estimated that approximately (93.0±4.1)% of the administered dose was absorbed after microspheres injection in 4 dogs. There were no serious adverse effects other than light tissue irritation. CONCLUSIONThis NTX microspheres preparation provides a safe, complete and sustained release of the drug for about one month.

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.