The intracellular signal transduction pathway of histamine H 3 receptor was reviewed. The modulatory effect to some neurotransmitters on cardiovascular system and the therapeutic potential of histamine H 3 receptor agonist was summarized.

Objective To study the changes of colonic motility in chronic stress-induced depression rat model,the association between interleukin 6 (IL-6) and depression and its effects on contraction of colonic smooth muscle in vitro.MethodsThere were 30 healthy adult Wistar rats,of which chronic stress-induced depression model was created in 15 rats and the other 15 rats were in control group.The ratio of sugar consumption to body weight and the percentage of sugar preference were tested in these two rats groups through sugar preference experiments.The behavioral changes of two rats groups were detected by open field test.Colonic motility was evaluated with simulated fecal discharge experiment,and the serum IL-6 level was measured with enzyme linked immunosorbent assay (ELISA).IL-6 in colon tissue at mRNA level was determined by RT-PCR.The contraction ability of rat colonic smooth muscle was observed.The colonic smooth muscle of control group was treated with different concentration of IL-6,the effects of IL-6 on normal colonic smooth muscle and its response to acetylcholine (Ach) were evaluated.Results In model group,the ratio of sugar consumption to body weight was 0.12±0.03,the percentage of sugar preference was 16.17％ ±2.61 ％,total walking distance was (741.54 ± 341.10) cm and total times of upright was 15.69 ± 8.00,which were all significantly lower than those of control group (0.18±0.02,25.54 ％ ± 2.32 ％,1336.20 cm±698.80 cm and 24.87±7.90,respectively) (P=0.041,0.044,0.002 and 0.001).It took (109.78±48.00) min for defecating in model group,which was significantly longer than that of control group (28.00±11.10) min (P=0.002).The IL-6 levels were high both in the serum and colon tissue of model group rats.The response of colonic smooth muscle to Ach was weaker in model group than that of control group (P=0.035).In model group,there were no significant difference in the response of colonic smooth muscle to IL-6 at 200,500 and 1000 pg/ml (P =0.935、0.825、0.766 ).After Ach added,there was significant difference in the response to Ach between IL-6 at 500,1000 pg/ml (R=1.1480±0.1000 and 1.1361±0.1500) and control group only added with Ach (R=1.6100±0.4500) (P=0.000 and 0.004).ConclusionIL-6 level increase in chronic stress-induced depression rat model and causes smooth muscle contraction disorder through reducing the sensitivity of intestinal smooth muscle to Ach.

Objective To detect the location of histamine in peripheral sympathetic nerves of guinea pig. Methods Histidine decarboxylase mRNA was detected using in situ hybridization histochemistry with specific oligonucleotide probe,while histamine and tyrosine hydroxylase were detected using double labeled immunohistochemistry with anti-histamine antibody and anti-tyrosine hydroxylase antibody in the superior cervical ganglia of guinea pig. Results The histidine decarboxylase mRNA hybridization signal were detected in both of large and small cells.The TH immunoreactive substance distributed in cytoplasm steadly,but lacked in the nuclei,while the histamine immunoreactive substance distributed in cytoplasm nearby the plasmalemma.After chemical destroy of the guinea pig SCG′s neuron with 6-OHDA,the immunoreactive materials were hardly detected.Conclusion Because the histidine decarboxylase is the only enzyme which catalyzes histidine into histamine,histamine may be synthesized and coexisted with monoaminergic neurotransmitters in the superior cervical ganglia of guinea pig.

Objective To investigate the expression of histamine in the cardiac sympathetic fibers from the guinea pig superior cervical ganglion and its coexistence with norepinephrine so as to provide morphological evidence for histamine as a cardiac sympathetic neurotransmitter.Methods Biotinylated dextranamine(BDA) anterograde tracing and immunofluorescence histochemical staining for histamine/norepinephrine were applied.Results After injection of BDA into the superior cervical ganglion,BDA labeled sympathetic fibers in the left and right atria and ventricle were observed.Meanwhile,the tracing fibers proved histamine-like immunoreactive or both histamine and norepinephrine-like immunoreactive.Conclusion Histamine is expressed in the cardiac sympathetic fibers from the guinea pig superior cervical ganglion and coexisted with norepinephrine.

Objective:To explore the application value of case three-dimensional teaching method combined with standardized patient (CTTM+SP) in the clinical clerkship teaching reform of gastrointestinal surgery.Methods:A total of 120 students of clinical medicine having clerkship in Binzhou Medical University Hospital were recruited in this study, and they were randomized to the experimental group and the control group, with 60 students in each group. The experimental group took the CTTM+SP teaching method, and the control group adopted the lecture-based learning teaching method. The comprehensive ability of the two groups was evaluated by department graduation examination and satisfaction survey.Results:The examination performance and the satisfaction rate of students in the experimental group were significantly higher than those of the control group ( P < 0.05). Conclusion:CTTM+SP teaching method is helpful for the probationers to master the theoretical knowledge of gastrointestinal surgery systematically, improve the clinical thinking ability and the ability to solve practical problems, mobilize the students' learning motivation and interest, and improve the teaching effect of gastrointestinal surgery clinical clerkship.

Objective:To investigate the improved superantigen activity of SEC2(T20L/G22E) compared with recombinant staphylococcal enterotoxins C 2 ( rSEC2 ).Methods: The proliferation of spleen lymphocytes and T-cell subpopulations induced by rSEC2 and SEC2(T20L/G22E) were examined by WST-1 and flow cytometry separately,and the gene expression of cytokines and Vβspecificities were quantified by real-time PCR.Results: WST-1 and Flow cytometry assays showed that the superantigen activity of SEC2(T20L/G22E) was improved due to enhanced T-cell stimulating potency,resulting in massive activation of T-cells,particularly CD4+and CD8+T-cells.Quantitative real-time PCR assay showed that despite similar Vβspecificities induced by rSEC 2 and SEC2 (T20L/G22E),the quantities of activated T-cells bearing specific Vβwere different,and SEC2(T20L/G22E) could stimulate more gene expression of associated cytokines simultaneously.Conclusion: The results strongly suggested that the increased SEC 2 ( T20L/G22 E)-TCR-binding affinity contributed to more T-cells activation and cytokine release ,which elicit powerful immune activition.

Objective To investigate the role of Zn 2+and Zn2+-coordinating glutamic acid residues ( 71Glu and 80Glu ) in the superantigenic activities of staphylococcal enterotoxin C2 ( SEC2 ) .Methods Over-lap PCR was used to amply genes encoding recombinant mutant proteins rSEC 2 ( E71A), rSEC2 (E80A) and rSEC2 (E71A/E80A).The mutant proteins were expressed in E.coli BL21 (DE3) and puri-fied by affinity chromatography .The differences of biological activities between rSEC 2 and its mutants were compared in vitro.The effects of Zn 2+on the superantigenic activities of rSEC 2 were evaluated by analyzing the proliferation of splenic lymphocytes in the presence or absence of ethylenediaminetetraacetic acid ( EDTA) .Results The substitution of glutamic acid residue at position 71 and 80 by alanine residue had no significant effects on the superantigenic activities and the conformational stability of rSEC 2 mutants.How-ever, traces of Zn2+(10μmol/L) could significantly enhance rSEC2-induced proliferation of splenic lympho-cytes, and only certain amount of Zn 2+could completely restore rSEC2-induced proliferation in the presence of EDTA.Conclusion This study indicated that mutations at Zn 2+-coordinating glutamic acid residues had no significant effects on the conformational stability and the superantigenic activities of SEC 2.Zn2+might play a role in regulating the superantigenic activities of SEC 2 through some indirect ways .

A tumor-targeting recombinant fusion immunotoxin B-L-SEC2 was constructed by fusing staphylococcal enterotoxin C2 (SEC2) and an anti-HER-2 single-chain Fv B1 through a peptide linker, and expressed in E. coli strain BL21 (DE3) with an improved expression vector pASK75-EX as inclusion body. The denatured inclusion body was purified with Ni-NTA chelate agarose, and then re-natured by dialysis. FACS and MTT assays indicated that the re-natured fusion immunotoxin B-L-SEC2 could target the HER-2 over-expressing breast tumor cell SK-Br-3 in vitro, and inhibit the growth of SK-Br-3.

Objective A prospective randomized controlled trial was carried out to explore the best time of In-domethacin suppositories administration for the prevention of post-ERCP pancreatitis in high-risk groups. Methods 81 patients were enrolled in the study finally. Patients were randomized into group A (100 mg rectal Indomethacin suppositories was administrated immediately after ERCP), group B (100 mg rectal Indomethacin suppositories was administrated half an hour after ERCP) and group C (ERCP alone group, which did not give Indomethacin supposito-ries). The level of serum amylase, urine amylase, serum CRP, serum IL-6, serum TNF-α were measured before, 3 h, 24 h and 48 h after ERCP, and the incidence of PEP and hyperamylasemia were analyzed. Results There was 1 case (4.00%) of PEP in group A, 2 cases (5.41%) of PEP in group B and 5 cases (26.31%) of PEP in group C;the incidences of PEP of group A and group B were significant lower than that in group C (P < 0.05). There was 1 case (4.00%) of hyperamylasemia in group A, 5 cases (13.51 %) of hyperamylasemia in group B and 6 cases (31.6 %) of hyperamylasemia in group C, and the incidences of hyperamylasemia of group A and group B were significant lower than that in group C ( P< 0.05). Conclusion Administration of 100 mg Indomethacin suppositories immediately or half an hour after ERCP can effectively reduce the incidence of PEP and hyperamylasemia.

Objective To examine the clinical effect of phacoemulsification with foldable posterior chamber intraocular lens implantation (PC-IOL) in management of angle-closure glaucoma (ACG) with cataract. Methods Phacoemulsification with foldable PC-IOL implantation was performed in 31 eyes with ACG. The best corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber depth (ACD) and anteior chamber angle width were measured and recorded preoperatively, 1 day, 1 week, 1 month and 3 months postoperatively. Results The mean IOP decreased significantly after surgery (P