G protein coupled receptors (GPCR) are important transmembrane proteins which account for more than 30% of direct clinical drug targets. Two main signaling pathways, either mediated by different G protein subtype or arrestins, underlies most of 800 GPCR functions in human genome. Selective ligands targeting to one of the G protein or arrestin signaling through specific receptor, which is also called biased ligands, may have beneficial effects and delete the unwanted side effects compared with traditional full agonists or antagonists. However, the mechanism governing the arrestin mediated GPCR biased signaling is still unclear. In recent years, our research group have combined animal models, cell biology and biophysical approaches to address the arrestin mediated GPCR function and its underlying mechanism, which is a key issue for GPCR targeted drug discovery. We have identified that downstream of β2 adrenergic receptor, arrestin mediated signaling plays critical roles in maintaining the pancreatic islet homeostasis and promotes the learning and memory through regulation of astrocyte-neuron lactate transportation cycle. Targeting β- arrestin- 1 signaling rather than Gq signaling down?stream of CCK1R receptor may provide a better therapy for diabetes. Although arrestin mediated signaling was traditionally recognized as the second wave of GPCR signaling, our recent results indicated that β-arrestin-1 was able to induce the first wave signaling in to regulate the catecholamine secretion from adrenal gland, by directly mediating AT1R/TRPC3 coupling. This result provided new mode for the connection of GPCR to activation of ion channels. Moreover, all above arrestin mediated signaling are regulated by receptor phosphorylation barcode, a hypothesis brought up by Prof. Lefkowitz and Prof. Andrew Tobin. Using biophysical and cellular approaches, we have identified that the 10 distinct phosphorylation interacting sites along the N-terminal of arrestin is the ″phospho-code″ reader of the arrestin, which recognized the information passed by GPCR, then translated to more than 1000 distinct arrestin conformations, and recruit distinct downstream signaling molecule. We therefore proposed″a flute model″ working mechanism for arrestin mediated GPCR signaling. Using this flute model combined with GPCR ligand identification, we were able to regulate specific signaling and therefore arrestin mediated physiological functions by activation of the receptor and operation of the receptor phosphorylation barcode simultaneously (unpublished results). These knowledge advances in arrestin mediated GPCR signaling may facilitate further drug development targeting to GPCR family members.

Objective To investigate the expression of ?-catenin protein in colorectal cancer. Methods Thirty-six CRC cases underwent radical operation from February 2001 to September 2001, ?-catenin protein expression was studied with immunnohistochemistry. ?-catenin mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). The correlation between ?-catenin protein expression and CRC clinical pathological factors was studied. Results ?-catenin protein expression was positive in 30 CRC cases ( 83. 3% ) , and 2 cases ( 5. 6% ) in normal colorectal epithelium cells ( P

Objective To establish an HPLC method for the determination of lobetyolin in Shengmai Granules. Methods ZORBAX SB-C18(250mm×4.6 mm,5μm) column was used, the mobile phase consisted acetonitrile:0.1% acetic acid (22:78, v/v), the flow rate was 0.8 ml/min, the column temperature was 30℃ and the detecting wavelength was 267 nm. Results The cablibration curve showed good linear relation within a range of 0.082～ 1.640 mg/ml, the average recovery was 98.5% and the RSD was 0.70%.Conclusion The method was simple, repeatable and accurate. It can be applied in quantitative determination of lobetyolin in Shengmai Granules.

Objective To investigate the value of prostate-bladder angle (PBA) measured by MRI in the diagnosis of benign prostate obstruction (BPO). Methods A retrospective analysis was carried out on 87 benign prostatic hyperplasia (BPH) patients referred for lower urinary tract symptoms (LUTS) between March 2009 and November 2009. PBA was measured by MRI and urodynamic parameter Qmax was measured as well. With the diagnostic criteria of BPO as Qmax＜10 ml/s, the patients were divided into two groups: obstruction group and non-obstruction group. PBA was compared between these two groups. The sensitivity and the specificity of PBA in diagnosing BPO were also analyzed. Results The age range of the patients was 57-90 years with a median age 73 years; Qmax was 2.325.4 ml/s with median Qmax 7.9 ml/s; PBA was 4°-52° with median PBA 27°. There were 25 patients in the non-obstruction group with PBA between 4°- 21°(13°); in the obstruction group,there were 62 patients with PBA between 15°- 52°(34°). PBA was found statistically different between the obstruction and non-obstruction group (P＜0.01). With the cutoff at PBA≥20°for the diagnosis of BPO, the sensitivity and specificity of the diagnosis were 90. 3 % (56/62)and 96.0% (24/25), respectively. Conclusion PBA measured by MRI is valuable and can be used as a new non-invasive parameter in the diagnosis of BPO.

Hepatic ischemia/reperfusion injury is an important restricting factor of clinical liver resection and liver transplantation.When the liver is transiently deprived of blood followed by repeffusion,a large number of various mediators are released that can lead to cellular and,eventually,organ dysfunction.This review summarizes the pathogenesis and the protection mechanisms of hepatic ischemia/reperfusion injury.

Objective To explore the oxidative stress pathogenesis of Parkinson's disease(PD) induced by paraquat in substantia nigra of mice. Methods The model of PD was established by oral administration of paraquat to mice.The spectrophotometry was used to determine the activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-PX) and the content of malondialdehyde(MDA) in substantia nigra.At the same time,number of tyrosine hydroxylase(TH) positive neurons in substantia nigra of mice was estimated by immunohistochemistry. Results The activities of SOD and GSH-PX were significantly decreased,and the content of MDA was increased in paraquat-treated mice compared to that of mice treated by saline taken orally(P

Objective To set up a clean-up method using gel permeation chromatography(GPC)and ENVI-Carb-SPE.The residues of triadimefon and its metablites,triadimenol A and triadimenol B in ginseng were detected by GC-MS with negative chemical ionization(NCI).Methods The sample was extracted with acetone and the extract was cleaned using GPC and ENVI-Carb-SPE.Based on GC-MS(NCI)the pesticides were separated on a DB-5MS column using a temperature program and were detected with a mass selective detector in selective ion monitoring(SIM)mode.The reference solution was prepared by the blank sample extract to overcome the matrix effect,the external reference method was used to detect.Results Three pesticides were separated within 10 min.The average spiked recoveries in three levels were 90%—105% with relative standard deviations(RSD)below 6%(n=6)in roots and stems.The limits of detection(LOD)of triadimefon and triadimenols were 0.1 and 10 ?g/L.The precision was below 2%(n=6).Conclusion The method is sensitive for the residue analysis of three pesticides and could be used to the triadimefon and triadimenols detection and security control in ginseng.

Objective To study the effect of interventional treatment on the expression of PgP and GST ? in different histopathological types of primary lung carcinoma. Methods One hundred and eighteen cases of histopathologically verified primary lung carcinoma were studied. SCLC was found in 26 cases and NSCLC in 92 cases. The non chemotherapy group had 50 cases, and the interventional treatment group had 68 cases. PgP and GST ? were examined in all specimens with 2 step immunohistochemistry. Results The positive expression rates of PgP and GST ? were 32.0% and 34.0% in non chemotherapy group, respectively, 75.0% and 78.6% in interventional treatment with non embolization group, respectively, and 50.0% and 52.5% in interventional treatment with embolization group, respectively. The positive expression rates of PgP and GST ? had significant difference between non chemotherapy group and interventional treatment with non embolization group( P 0.05). There was a tendency of positive correlation between differentiated degree of carcinoma and the expression of PgP and GST ? in NSCLC. Condusion To detect PgP and GST ? in carcinoma tissue is important and has the instructive significance for chemotherapy of lung carcinoma. The positive rate of multidrug resistant gene is obviously increased in the primary lung carcinoma with bronchial arterial chemotherapy. The inducement to multidrug resistance gene in bronchial arterial embolization with the emulsifying agent of oil anticarcinogen was lower.

Benzene ; poisoning ; Hazardous Substances ; Humans ; Occupational Exposure ; prevention & control

Objective To explore the safety and effectiveness of percutaneous vertebrophasty(PVP)in the treatment of the metastatic tumor involved axis.Methods Ten patients(8 male,2 female)with osteolytic metastases involved axis were treated with PVPs.The anterolateral approach with fluoroscopy guidance was selected in 9 cases,while the posterolateral approach with CT guidance was selected in 1 case.Results Successful unilateral-paracentesis for PVP were achieved in all patients without intervention related complications such as bleeding and symptomatic polymethylmethacrylate(PMMA)leakage.CT scan taken following PVP showed that over 70% of the osteolytic metastatic area was well filled with PMMA in all cases.Varying degrees of pain relief were observed(CR in 7 cases,PR in 3 cases)within 7 days.All patients could support their heads without brackets.During a 3 to 24 months follow up after the procedures,No aggravated pain was found in the group.Two patients died in 4 months,3 Patients died in 8 to 11 months 4 patients died in 13 to 15 months,and 1 patient still was alive after 24 months.Conclusion Anterolateral or posterolateral approach to Aixs in PVP is safe and effective in treating osteolytic metastatic tumors.