Multinolular and intrahepatic recurrent HCC can originate from intrahepatic metastasis and multiple origins,and their colnal origin is closely related to the clinical diagnosis and treatment.To designate suitable therapeutic strategies according to their colnal origin is a new challenge needs to be tackled urgently.This paper reviews recent progress in the clinicopathological features,molecular diagnosis and clinical outcomes of multiple origin HCC.

CCK receptor belongs to G-protein-coupled receptor (GPCR) superfamily.Polymorphism of CCK receptors can alter drug affinity and/or biological efficacy, and its genetic differences in amino acid sequences can induce ligand-independent signaling, which in turn can lead to disease. With growing efforts in the field of pharmacogenomics, it is anticipated that polymorphism-induced alterations in drug and/or receptor function will be a focus of increasing concern in the future drug-development project. Study of CCK receptor polymorphism may reveal some universal rules in GPCR superfamily. In this review, the alterations of receptor function and/or drug efficacy resulted from polymorphism in CCK receptors will be discussed in the viewpoint of molecular biology and pharmacogenomics, and some strategies in development of receptor-specific drugs will be put forward.

Objective To investigate the contents of cAMP and cGMP in the central nervous system in morphine dependent and withdrawal rats.Methods A physical morphine dependent model in rats was established by subcutaneous injection of morphine in gradually increasing doses.The cAMP and cGMP contents in the brain regions were determined by radioimmunoassay.Results Compared with control group,morphine dependence could significantly decrease the cGMP content or profoundly increase the cAMP content and the cAMP/cGMP ratio in rat striatum,diencephalons,midbrain,pons and hippocampus,but these changes described above were not detected in cerebellum.Compared with morphine dependent group,naloxone induced withdrawal could significantly decrease the cGMP contents or increase the cAMP contents and the cAMP/cGMP ratio in striatum and hippocampus,but these changes described above were not observed in the other regions.Conclusion The changes of the cAMP and cGMP contents may be one of the important molecular mechanisms leading to morphine dependence and abstinence.

Objective To investigate the role of Stat1 in pathological process of nerve cells apoptosis induced by diffuse axonal injury (DAI) on rats. MethodsThe DAI model was established by using an injury model adapted from Marmarou et al. in 1994. All animals were divided into three groups, including control group, mock group and test group sacrificed on 6, 12, 24, 48, 72, 120 and 240 hours post injury (hpi). The paraffin-embedded sections of brain tissue were processed for HE staining and Bielschowsky’s silver method. Cell apoptosis was examined by flow cytometry and the expression of bax and bcl-2 were analyzed by RT-PCR. And Phospho-Ser727 Stat1 expression was examined by immunohistochemistry in different brain regions. ResultsThere was no brain contusion within HE staining, however, waving and enlargement of axons were observed within Bielschowsky’s silver method. The apoptotic rate of brain cells as well as PCR products ratio of bax to bcl-2 was highest at 24 hpi and decreased with time. An up-regulation of Phospho-Ser727 Stat1 at 6 hpi was discernible, and then reached the top at 24 hpi in cortex, cerebellum, brain stem and corpus callosum, and at 12 hpi in hippocampus. This increase was associated with the nerve cells apoptosis, r=0.921. In addition, the Phospho-Ser727 Stat1 positive cells were neurons and glial cells assessed from morphous. ConclusionsOur data indicate that Stat1 may contribute to the apoptosis of DAI on rats. In addition, the expression of Phospho-Ser727 Stat1 in glial cells suggested that glial cells may play an important role in the pathogenic mechanism of DAI.

Recent studies show that cholecystokinin, a brain-gut peptide, also locates in lung tissues in many animals. Cholecystokinin in lung tissues participates in the modulation of the tone of the tracheae and the pulmonary vessels. It also regulates the breathing pattern as a nerve transmitter in the respiratory center. This paper discusses the location and the biological role of cholecystokinin in lung tissues and focuses on its part during lung diseases.

Animals ; Arrhythmias, Cardiac ; etiology ; therapy ; Captopril ; therapeutic use ; Disease Models, Animal ; Electric Stimulation Therapy ; methods ; Myocardial Ischemia ; physiopathology ; therapy ; Rabbits ; Ventricular Fibrillation

AIM: To explore the effect of peroxynitrite (ONOO -) on pulmonary microvascular endothelial barrier and roles of ONOO - in the pathogenesis of acute lung injury in vivo. METHODS: SD rats in different groups were insufflated with various concentrations of ONOO -, decomposed ONOO - or vehicle (alkaline normal saline), respectively. Then permeability changes in pulmonary microvascular walls were detected and the pathological alterations of pulmonary tissue were examined under light microscope. Malondialdehyde(MDA) contents were measured in normal lung homogenate pretreated with various concentration of ONOO -. RESULTS: Intratracheal insufflation of ONOO - resulted in dose-dependent increase in lung coefficient, lung wet/dry ratio, lung water contents and Evans blue contents, together with significant pulmonary pathological changes such as diffuse alveolar collapse, capillary congestion, focal hemorrhage, and endothelial swollen. In addition, ONOO - can also elicit increase in MDA contents in normal lung homogenate. CONCLUSION: ONOO - may induce dysfunctions of pulmonary microvascular endothelial barriers, it is suggested that enhanced endogenous ONOO - generation may take part in the pathogenesis of acute lung injury.

Objective To study the receptors signaling of prostaglandin E2 on the differentiation of regulatory T (Treg) cells and Th17 cells.Methods The expression of prostaglandin E2 receptors (EP1/EP2/EP3/EP4) on the MACS-purified CD4+CD62L+ T (Th0) cells was analyzed by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR).The quantity of CD25+Foxp3+ cells was examined by flow cytometry,the expression of FoxP3 mRNA and RORγt mRNA were detected using real-time RT-PCR,the level of IL-17 in the culture supernatants was detected by enzyme-linked immunosorbent assay (ELISA).ANOVA,LSD-t,Dunnett T3 were used for statistical analysis.Results EP1,EP2,EP3,EP4 were expressed on Th0 cells at different levels,and EP2 [(89.7±9.1)％] had the strongest expression.PGE2 [(3.0± 2.2) ％],EP2 agonist [(4.5± 1.0) ％] and EP4 agonist [(8.8 ±2.5) ％] decreased the quantity of CD25 +Foxp3 + cells compared with the control group [(28.6±6.8)％] (t=7.156,P=0.021; t=6.958,P=0.032; t=5.359,P=0.044).PGE2(0.210±0.020),EP1 agonist (0.833±0.045),EP2 agonist (0.227±0.025) and EP4 agonist (0.450±0.060) decreased the expression of Foxp3 mRNA compared with the control group (1.000) (t=23.817,t=5.026,t=23.313,t=16.581; all P=0.000).PGE2 [(22±6)pg/ml],EP2 agonist [(24±5)pg/ml]and EP4 agonist [(207±19) pg/ml] decreased the secretion of IL-17 compared with the control group [(678±87) pg/ml] (t=14.925,P=0.004; t=14.873,P=0.004; t=10.480,P=0.008).PGE2 (0.141±0.027),EP1 agonist (0.869±0.033),EP2 agonist (0.176±0.029) and EP4 agonist(0.371±0.042) decreased the expression of RORγt mRNA compared with the control group (1.000) (t=34.046,t=5.184,t=32.673,t=24.962,all P=0.000).Conclusion EP1,EP2,EP3,EP4 receptors are expressed on CD4+CD62L+ T (Th0) cells at different levels.Prostaglandin E2 inhibits the differentiation of Treg cells and Th17 cells via the EP2 and EP4 receptors signaling.

0.05).But PMA increased and SC-3088 decreased cAMP content and PKA activity in LPS-stimulated rat PIMs(P

Aim To investigate the hippocampal neuronal injury induced by ?-amyloid peptide ( A?) in rats and the candidate contribution of JNK signal transduction pathway to A? toxicity. Methods Rats were bilaterally injected with A?1 -40 into hippocampi CA1 area. The pathological changes,survival and apoptosis,and ultrastructure of hippocampal neurons,as well as p-JNK positive cells were observed by HE staining,Nissl staining,TUNEL staining,immunohistochemistry and transmission electron microscopy,respectively. Results Thepyramidal cells in hippocampus arranged loosely with decreased cell number. The gliacytes significantly proliferated. Significant apoptotic features were observed in CA1 ultrastructure. TUNEL-positive cells and p-JNK-positive cells significantly increased ( P