Objective:To observe influence of enhanced external counterpulsation (EECP) on plasma levels of lipo‐protein-associated phospholipase A2 (Lp‐PLA2) and hsCRP in patients with coronary heart disease (CHD) ,and preliminarily explore anti -inflammatory mechanism of EECP in prevention and treatment of CHD .Methods :A to‐tal of 85 CHD patients were selected from our hospital ,randomly divided into routine treatment group (n=42) and EECP group [n=43 ,received EECP based on routine treatment ,once/d ,60min each time ,continuous five weeks were regarded as one course (35 times)] .Plasma concentrations of Lp‐PLA2 and hsCRP were measured in all sub‐jects at the enrollment day and after five -week treatment .Results:Compared with before treatment ,after five-week treatment ,there were significant reductions in plasma levels of Lp‐PLA2 [(58.46 ± 40.04)μg/L vs .(33.94 ± 23.22)μg/L] and hsCRP [ (3.54 ± 2.22)μg/ml vs .(2.19 ± 1.16)μg/ml] in EECP group (P<0.01 both) ,and there were no significant difference in routine treatment group between before and after treatment .Compared with routine treatment group ,after five-week treatment ,there were significant reductions in plasma levels of Lp‐PLA2 [ (56.87 ± 33.69)μg/L vs .(33.94 ± 23.22)μg/L] and hsCRP [ (3.63 ± 1.60)μg/ml vs .(2.19 ± 1.16)μg/ml] in EECP group , P<0.01 both .Conclusion:1. EECP of one course can significantly reduce plasma concentrations of Lp‐PLA2 and hsCRP in CHD patients , indicating that anti - inflammatory may be one of its mechanism in preven‐tion and treatment of CHD .

Objective To evaluate extracellular and intracellular IFNγ and IL-4 levels in assessing Th1/Th2 balance in children with chronic hepatitis B (CHB) and asymptomatic carriers.Methods Fiftyfour hospitalized children including 23 CHB patients and 31 asymptomatic carriers were collected from May 2007 to February 2009.Thirty-four healthy children were served as control.Serum IFNγ and IL-4 levels were measured by enzyme-linked immunosorbent assay (ELISA) and intracellular IFNγand IL-4 levels were detected by flow cytometer.Analysis of variance (for homogenous variance) and Kruskal-Wallis test (for non-homogenous variance) were performed.Results The differences on extracellular IFNγ, IL-4 and Th1/Th2 among CHB, asymptomatic carriers and control groups were not statistically significant (F=0.342, 0.020 and 0.507, P ＞ 0.05); while the intracellular IFNγlevels were (7.68 ± 4.62), (11.71 ±4.36) and (13.61 ±6.71) μg/mL, and Th1/Th2 ratios were 0.96 ±0.30, 1.67 ±0.76 and 2.11 ± 1.12in three groups respectively (F=0.255 and 0.140, P ＜ 0.05 or ＜ 0.01).The differences in intracellular IL-4 levels among three groups were not significant (F=0.425, P ＞ 0.05).Conclusions Cytokine balance is affected in CHB children and asymptomatic carriers, and flow cytometry analysis is considered as a better method in evaluating the status of Th1/Th2 balance.

Objective To study the preparation of 131 I-nalepride and its characters in small animal in vivo ,and to evaluate the feasibility for its application in diagnosing neuropsychiatric disease .Methods s-5-(tributyltin)-N-[(1-ethyl-2-pyrrolidinyl) meth-yl]-2 ,3-dimethoxy-benzamide was used as the labeled precursor .The hydrogen peroxide method was adopted to label131 I-nalepride . The bio-distribution character test in ICR mice was performed .SD rats were performed the blocking experiment and the cerebral au-toradiography .Results The radiolabeled yield and radiochemical purity were over 95% .The results of the bio-distribution character test showed that the striatum had the highest uptake .The striatum to cerebellum uptake radio(ST/CB) reached 111 .87 at 4 h after injection and the maximum ST/CB value of 416 .97 at 12 h after injection .Regional brain autoradiography showed that the optical densities were significantly decreased from 7 .43 ± 0 .86 to 1 .07 ± 0 .18 after injection of 131 I-naleprid(P<0 .05) .These results indi-cated that 131 I-nalepride had specific binding to the dopamine D2 receptor .131 I-nalepride was rapidly uptaken by organs after injec-tion .The initial uptake in liver and kidney were higher and the % ID/g values were 14 .82 ± 3 .88 and 10 .28 ± 1 .65 receptively .The tracer was cleared out from the organ quite rapidly .Conclusion 131 I-nalepride has the high affinity and specificity to dopamine D2 receptor ,which could be used as the EPECT imaging agent of dopamine D2 receptors and as a tool drug to screen and evaluate the affinity of other antipsychotic agents to dopamine D2 receptors .

AIM:To establish a new rat model of depression by the antagonistic relationship of antagonizing pairs of neurotransmitters in the brain.METHODS:Dopamine D1 receptor antagonist SCH23390 was injected into the hippocampus of the rats by microinjection at low, medium and high doses (1, 2 and 4 g/L) to establish a depression model.After modeling, the sucrose consumption, open-field and novelty suppressed feeding tests were used to evaluate the behaviors of the rats, and screen out the best modeling drug dose.The model of depressive rats was induced using the best modeling drug dose and the model rats were observed for 2 weeks.The stability of the model was evaluated by behavioral tests, and the contents of IL-1β and TNF-α in cerebrospinal fluid (CSF) were measured by ELISA to evaluate the safety of the model.The levels of the antagonizing pairs of neurotransmitters in the cerebral cortex and hippocampus were analyzed by the method of high-performance liquid chromatography-mass spectrometry (HPLC-MS), so as to evaluate the pathological characteristics of neurotransmitter imbalance in the brain of the model rats.RESULTS:After modeling, the rat weight, sucrose preference rate, and horizontal motion and vertical motion scores of open-field test were significantly decreased in eACh dose model group, and feeding latent periods of novelty suppressed feeding test were significantly increased, indicating a typical depressive behavior.The rats with the medium dose (2 g/L) of SCH23390 had the most significant depressive behavior.At 2 weeks after modeling, compared with the normal control group, the weight, sucrose preference rate, and horizontal motion and vertical motion scores in medium dose group were significantly decreased (P<0.01), while the feeding inhibition time was significantly increased (P<0.05).No significant difference in the content of IL-1β and TNF-α in the CSF of normal control group, blank control group and medium dose group was observed, indicating that the model did not cause obvious inflammatory injury, and the modeling method was safe.Compared with blank control group, the contents of 5-HT, NE and Glu in the left hippocampus of rats in medium dose group were significantly increased (P<0.01), and the content of DA and ACh showed decreasing trends.The contents of 5-HT, NE and Glu in the right hippocampus of the rats were significantly increased (P<0.05), and the contents of DA and ACh showed decreasing trends.The content of Glu in cerebral cortex was significantly increased (P<0.05), the contents of 5-HT and NE showed increasing trends, and the contents of DA and ACh showed decreasing trends, indicating that the model was basically consistent with the pathological features of neurotransmitter imbalance in the brain of depression.CONCLUSION:This method can successfully replicate the rat model of depression, which has the characteristics of typical and persistent symptoms, fast modeling, and safe and easy operation.Using the dosage of 2 g/L is more suitable.

Objective To study the therapeutic and toxic effects of 32 P-chromic phosphate-poly (L-lactic) acid (32p-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma.Methods Twenty four nude mice bearing tumors were injected with 0,9.3,18.5 and 37.0 M Bq 32p-CP-PLLA microparticle,respectively.The relative tumor growth rates were observed every day,and white blood cells,platelets and body weight were measured.At 14 d after administration,the tumors were removed,histological examination and immunohistochemical analysis were performed.Results The relative tumor growth rates of each treatment group was lower than 40％.Histological examination showed the degenerative necrosis at the site nearby the mircoparticle.Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast,the expression of bax in treated group were higher than those in control group.The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43,0.47 ± 0.13,1.10 ± 0.32,2.19 ± 0.57 for 0,9.3,18.5 and 37.0 MBq 32 P-CP-PLLA microparticle,respectively ( t =2.36 - 2.77,P ＜ 0.05).MVD were 31.2 ± 2.3,23.8 ± 1.5,14.8 ±0.8,11.0 ± 1.2,respectively.Dose dependence was observed in both HE and IHC staining after 14 d treatment ( t =2.30 - 2.57,P ＜ 0.05 ).Conclusions Intratumoral injection of 32p-CP-PLLA microparticle might be a safe,easy and effective radionuclide interventional therapy for pancreatic carcinoma.

Objective To investigate the productive effects of baicalin on the male rats with ischemic brain injury and its effects on serum progesterone level in rats; To explore the possible mechanism of baicalin in brain protection. Methods Adult SD male rats were used to create a permanent left middle cerebral artery occlusion model. The rats were evenly divided into model group, baicalin group, inhibitor group, and sham-operation group (without inserted into the intraluminal thread) according to the neurological function scores. At different time points after modeling, the neurological function scores and the grip strength of double foreleg were measured, and the reduction rate of grip strength was calculated. Serum progesterone and adrenocorticotrophic hormone (ACTH) were detected by ELISA. Results Compared with the sham-operation group, the neurological function of rats in the model group was impaired, the grip strength of double foreleg was significantly reduced. 7 days after treatment, compared with the model group, the neurological function score of baicalin group was lowered, grip strength of double foreleg was recovered, reduction rate of grip strength was reduced (P<0.05); compared with the baicalin group, protective effects of baicalin on neurological function was lowered in inhibitor group (P<0.05). 7 days after treatment, compared with the model group, the serum progesterone level in baicalin group was significantly higher (P<0.01), and ACTH level showed an increasing trend; compared with the baicalin group, serum progesterone and ACTH levels in the inhibitor group decreased (P<0.05). Conclusion The protective effects of baicalin on the male rats with ischemic brain injury may be related to the regulation of progesterone.

Objective To investigate the effects of baicalin on serum progesterone and related hormones in female normal and cerebral ischemia rats; To explore whether baicalin plays a role in cerebral protection of neurological functions by regulating progesterone levels.Methods With vaginal smear method, the adult estrus female SD rats were selected and divided into normal group, baicalin normal group, and molding groups. The left side of the middle cerebral artery of rats in the molding groups was blocked to establish the permanent middle cerebral artery occlusion (pMCAO). After modeling, the rats were randomly divided into model group, baicalin treatment group, progesterone treatment group and progesterone inhibitor group. The baicalin normal group and baicalin treatment group were given intraperitoneal injection of baicalin solution; the normal group and model group were given normal saline of the same quantity; progesterone treatment group was given intramuscular injection of progesterone; progesterone inhibitor group was given intraperitoneal injection of baicalin solution and intragastric administration of mifepristone solution.The neurological function deficit scores were evaluated and rat forelimb holding power was detected by Grip Strength Meter respectively at different time points. Serum was taken from the rats and the progesterone and related hormones levels in the serum of every group were measured by ELISA. Results Compared with normal group, neurological functions of rats in molding groups were damaged, and neural functional behavior scores of different time points were the most strongly increased (P<0.001), and rat forelimb holding power was the most strongly reduced (P<0.001). 5 days after treating, baicalin showed the trend of improvement of neurological functions (P>0.05) and more significant improvement of the forelimb holding power (P<0.01); 10 days after modeling, baicalin treatment group significantly increased neural functional behavior scorce (P<0.001) and the most significantly improved the forelimb holding power (P<0.001). Compared with baicalin treatment group, the progesterone inhibitor group had a significant inhibitory effect on neural functional recovery (P<0.05) 10 days after modeling, and the group also had a significant inhibitory effect on the recovery of holding power (P<0.05) 5 days and 10 days after treating. At the same time, compared with the model group, progesterone level in baicalin treatment group increased significantly (P<0.05), and FSH and LH decreased (P>0.05).Conclusion After applying mifepristone to block progesterone, baicalin neurologic protection is significantly inhibited. The results demonstrated that baicalin may play a role in cerebral protection via up-regulating serum progesterone level.

Objective To prepare a specific integrin αvβ3 probe 18F-Al-1,4,7-triacetic acid-1,4,7-triazacyclononane-2-(4-amino benzyl) thioamide-(3,6,9-trioxaundecanoic acid-11-amide)-(glutamic acid-cyclo(arginine-glycine-aspartic acid-phenylalanine-lysine) dimeric peptide) (18 F-Al-NOTA-PRGD2) and evaluate its feasibility for PET imaging in papillary thyroid carcinoma (PTC).Methods 18F-Al-NOTA-PRGD2 was synthesized by a novel Al18F complex strategy.Human PTC tissues were implanted into nude mice.Immunohistochemistry staining was performed to detect αvβ3 expression in human PTC tissues,xenografts in mice and adjacent normal tissues respectively.18F-Al-NOTA-PRGD2 with or without blocking agent of PRGD2 was injected via the tail vein into tumor-bearing mice (n =5) for microPET imaging.The radioactivity uptake in the tumor and major organs were measured via ROI technology.Biodistribution studies were also performed in tumor bearing mice (n=15) 30,60,120 min postinjection respectively.The two sample t test was used for statistical analysis.Results The labeling yield of 18F-Al-NOTA-PRGD2 was over 45％ (no attenuation correction) and the radiochemical purity was above 95％.The integrin αvβ3 expression was observed in human PTC both in situ specimens and xenograft in mice,while no expression was shown in the adjacent normal tissues.MicroPET imaging revealed that tumors were clearly visible with good tumor-to-background contrast.The radioactive uptake by tumor was (2.81 ±0.35) ％ ID/g,(2.45±0.27) ％ID/g and (1.80±0.21) ％ID/g at 30,60 and 120 min postinjection,respectively.In the presence of unradiolabeled PRGD2,the corresponding tumor uptake decreased to (0.51±0.05) ％ID/g at 60 min postinjection.High tumor uptake was also shown in the biodistribution studies,which was (3.09±0.25) ％ID/g,(2.75±0.37) ％ID/g and (1.90±0.16) ％ID/g at 30,60 and 120 min postinjection,respectively.The results were consistent with the microPET imaging results (t=1.456,1.465 and 0.847,respectively,all P＞0.0.5).18F-Al-NOTA-PRGD2 was rapidly cleared in blood and muscles,and the tumor to blood and muscle uptake ratios were 6.15±0.45 and 7.86±0.56 respectively.Conclusions 18 F-Al-NOTA-PRGD2 could be labeled easily and quickly with good labeling yield and radiochemical purity.Overexpressed integrin αvβ3 in PTC can be proved by both immunostaining and microPET imaging.18F-A1-NOTA-PRGD2 PET imaging might be a novel in vivo method for investigation of molecular mechanism in PTC.

Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.

OBJECTIVETo investigate the effect of betulinic acid (BA) on the proliferation, migration, apoptosis and cell cycle of pancreatic cancer cells (BxPC-3) in vitro and elucidate the underlying.

METHODThe effect of BA on the proliferation of BxPC-3 was measured by using sulforhodamine B (SRB) assay. Migratory ability of BxPC3 cells were detected by wound healing assay, and the morphological change was observed with light microscope. The influence of BA on cell cycle of BxPC-3 cells was tested by flow cytometry (FCM). Apoptosis was analyzed by using Hochest33342-PI double staining. Western blot technologies were applied to detect the expression of Bcl-2 and Bax.

RESULTBA exhibited significant cell proliferation and migration inhibition, as well as its potency of inducing apoptosis in BxPC-3 cells in vitro in a dose-dependent manner. The IC50 value for 72 h was 16.54 mg x L(-1). Cell migration was significantly inhibited at 5 mg x L(-1) of BA. Cells treated with BA showed increased cell population in G0 phase, with decreased G2/M phase population. The expression of Bax and Bcl-2 was up and down-regulated respectively in BA-treated BxPC-3 cells in a dose-dependent manner.

CONCLUSIONBA exerted potent effect on growth inhibition, G0 cell cycle arrest and induction of apoptosis in BxPC-3 cells in vitro, possibly associated with the down-regulation of Bcl-2 and up-regulation of Bax expression. The potent antitumor capacity of BA suggested that it could be a promising new anticancer agent in human pancreatic cancer treatment.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Pancreatic Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Triterpenes ; pharmacology ; bcl-2-Associated X Protein ; genetics ; metabolism