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.

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.

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.

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 changes of the white matter in adolescent depression by using the method of tract-based spatial statistics (TBSS). Methods We employed TBSS to examine WM microstructure in 35 treatment-naive adolescents with clinical depression and in 40 matched controls. By using the TBSS, we compared the difference of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) between theadolescent patients with depression and the controls. Results Our analysis revealed the abnormal WM microstructures in the clinically depressed adolescents. The whole-brain analysis revealed that patients, with lower FA values in the body of the corpus callosum (CC) (P < 0.01), had elevated RD and MD (P < 0.01), and preserved AD (P > 0.05). The FA values in the body of the corpus callosum was negatively correlated with the severity of depression (P < 0.01). Conclusions Our findings suggest that WM abnormalities are involved in the path-physiology of depression. Importantly , our findings show that these WM abnormalities present early in the course of the disorder.

Objective To evaluate the effects of dexmedetomidine on the expression of Toll-like receptor 2 (TLR2) and TLR4 in monocytes of blood during the perioperative period in the patients undergoing pulmonary lobectomy.Methods Fifty patients of both sexes, aged 40-64 yr, with body mass index of 20-24 kg/m2 , of ASA physical status Ⅰ or Ⅱ , scheduled for elective pulmonary lobectomy under general anesthesia, were randomized into 2 groups (n =25 each) using a random number table: control group (group C) and dexmedetomidine group (group D).In group D, dexmedetomidine was infused intravenously at dose of 1.0 μg/kg over 10 min before induction of anesthesia, followed by continuous infusion at a rate of 0.3 μg · kg-1 · h-1 until 30 min before the end of operation, while the equal volume of normal saline was given in group C.After admission to the operating room, at 1.5 h after beginning of operation, at the end of operation, and at 12 and 24 h after operation, blood samples were taken for blood gas analysis, and for determination of the expression of TLR2 and TLR4 in monocytes.Oxygenation index was calculated.The consumption of propofol and remifentanil and pulmonary complications within 48 h after operation were recorded.Results Compared with group C, the expression of TLR2 and TLR4 in monocytes of venous blood was significantly down-regulated, oxygenation index was increased, and the incidence of pulmonary complications after operation was decreased in group D (P＜0.05).Conclusion The mechanism by which dexmedetomidine attenuates acute lung injury is associated with down-regulation of TLR2 and TLR4 expression in monocytes of blood in the patients undergoing pulmonary lobectomy.

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.

Objective To explore the variation of E-index and M-index of rabbits with acute pulmonary embolism (APE) under the status of pulmonary hypertension (PHT). Methods Rabbit models of APE with PHT were established. A series of parameters [including peak early diastolic mitral inflow velocity (EM), peak late diastolic mitral inflow velocity (AM) and so on] were obtained with routine echocardiography and tissue Doppler imaging (TDI);and then E-index, M-index were calculated. The parameters before and after APE were compared. Results Twenty-three rabbit models with APE were successfully established, but 3 with atrial fibrillation were excluded. After APE, pulmonary artery pressure increased significantly, EM decreased observably, whereas right ventricular myocardial performance index (RVMPI) increased more evidently than left ventricular myocardial performance index (LVMPI) (P<0.01) did and E-index decreased and M-index increased remarkably. Conclusion Changes of E-index and M-index may provide reference for quantitative assessment of early APE.

Objective To summarize the imaging characteristics of the hepatic epithelioid hemangioendothelioma (EHE).Methods The clinical data of 6 patients with hepatic EHE who were admitted to the Yantaishan Hospital (3 patients), Zhangzhou Hospital of Traditional Chinese Medicine (2 patients) and Zhangqiu Hospital of Traditional Chinese Medicine (1 patient) between March 2007 and June 2014 were retrospectively analyzed.All the patients underwent plain scan and dynamic enhanced scan of computed tomography (CT), and the number,shape, size, location, density or signal, level and method of enhancement of the lesions were observed and analyzed.Six patients were followed up by outpatient imaging examination up to June 2014, and the changes of lesions were observed.Results Among the 6 patients, 1 solitary lesion and 5 multiple lesions were detected, and the total lesions were 125 including 1 patient with 75 lesions.The lesions were round or round-like and originated commonly from the right lobe of liver and hepatic subcapsular with a maximum diameter of 0.5-3.5 cm.Plain scan of CT showed that the lesions in 6 patients had low density with the clear boundary.MRI showed that low T1 WI signal and high or slightly high T2WI signal of the lesions were detected in 4 patients.Two patients had liver capsular retraction sign.The ring-like enhancement of 1 lesion and homogeneous enhancement of 5 lesions were found by dynamic enhanced scan of CT in 6 patients and enhanced scan of MRI in 4 patients.Enhanced signal in all the lesions was detected in the delayed phase.Veins into or through lesions were found in 3 lesions, with normal or narrowing vascular cavity.One patient had visible lollipop sign.Of the 6 patients, 5 were confirmed as with metastatic carcinoma of liver, and 1 was suggested as with cholangiocarcinoma.Six patients were diagnosed with hepatic EHE by pathological examination using hepatic biopsy technique.Among the 2 patients with hepatic EHE who didn't receive antineoplastic treatment after the diagnosis, 1 patient received CT examination at year 2 after first visit, which showed capsular retraction sign, and then was diagnosed as with secondary hepatic cirrhosis by MRI at 4 years after first visit.Another patient was diagnosed as with hepatic cirrhosis by CT examination at year 6.5 after first visit.One patient was diagnosed with tumor recurrence of hepatic left lobe by CT reexamination at postoperative year 4, and underwent ultrasound-guided radio frequency ablation (RFA) treatment based on no enlargement of tumor during 1-year follow-up, and then returned a normal condition after half year follow-up.Other 3 patients undergoing operation were followed up at postoperative year 1 , 4, 5 with no recurrence and metastasis.Conclusions Intrahepatic single or multiple nodules and delayed reinforcement by dynamic enhanced scan of CT and MRI are the typical imaging performances of hepatic EHE.There are certain characteristics in the liver the lollipop sign, capsular retraction sign and veins into or through the lesions.Mutual fusion and fibrosis of lesions leading ultimately to secondary liver cirrhosis may be characteristics of EHE growth.