Objective To improve scientific research capacity and disciplines development,we performed grading system to specialize and quantize the management in Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods With assistance of forum survey related to 20 clinical and technical departments in hospital,we assessed the status of disciplines development,designed assessment criteria,and revised relevant regulations in grading system.Results The implementation of grading system promoted scientific achievements,academic communications and human resource development in hospital as relative to their pre-implemental controls.Conclusions The implementation of grading system facilitates scientific research and improves disciplines development.

Objective:To research on the immune recognition mechanism of synthetic pyrethroids and generic specific antibody.Methods:We studied on quantitative structure-activity relationship ( QSAR ) of synthetic pyrethroids and their analogs as well as antibody activity ( IC50:fifty percent inhibition concentration ) using stepwise multiple linear regression method.Based on calculating structure descriptors of synthetic pyrethroids and their analogs , two-demensional QSAR ( 2D-QSAR ) model was established.The main factors affecting antibody activity were screened using 2D-QSAR,and predictive ability of QSAR models were evaluated by the method of leave-one-out( LOO) cross-validation.Meanwhile, the structure parameters of synthetic pyrethroid fragments were calculated and then analyzed using partial least squares ( PLS) assay.And then hologram QSAR ( H-QSAR) model was constructed on molecular substructure and antibody activity.The fragments contribution to antibody activity were illustrated by encoding different colors.Results:Decision coefficent (R2) of 2D-QSAR model and HQSAR model were 0.920 and 0.917 individually,cross-validation coefficient ( Q2 ) of two QSAR models were 0.875 and 0.660 respectively ,which showed two models had good predictive abil-ity.The result from 2D-QSAR model was also obtained that smaller was hydrophobicity of pyrethroids , easier was recognized by antibody.In addition,the optimum HQSAR model was constructed after we tried many combinations of these parameters .The fragment size in optimum HQSAR model was between 4 to 10,a hologram length was 61,optimum principle component was 4,and the fragment type of B/C/Ch was selected.However ,the fingerprint encoded results of synthetic pyrethroids weren′t consistent completely with exper-imental IC50 values.Conclusion:Hydrophobicity of synthetic pyrethroids is the largest correlation factors in antibody recognization .

In order to develop a safer vaccine strain exploit Salmonella Pullorum vaccine strain as a live vaccine vector.Methods:AΔcrpΔasd mutant of S.pullorum C79-13 strain was constructed and it was developed E.coli donor strain mutant was generated through the two-step method introduced by χ7213 ( pREΔasd) was conjugated with the recipient of C 79-13Δcrp.The C79-13ΔcrpΔasd the transduction of recombinant suicide plasmid .Results:PCR and sequencing results showed that ΔsipBSL1344 was suc-cessfully constructed.The further study indicated that foreign DAP must be supplied for the ΔcrpΔasd mutant to grow,in addition,the asd gene was transmitted stably .Compared with C79-13 strain,the O antigens was identical to C79-13 strain,but the growth velocity was reduced significantly ,significantly reduced virulence .Conclusion: The ΔcrpΔasd mutant can accept asd+plasmid to construct host-vector balance lethal system , and this system can be used to express foreign gene efficiently and to develop potential oral multivalent vaccines.

Objective:To explore the function of the cya gene and the preliminary mechanism of attenuated strain.Methods:The biological characteristics of cya mutant in acid and alkali resistant,salt resistance,motility,biofilm components,poisonous to the cells of epithelial cell adhesion,invasion were analysis.Results:The mobility capabilities,acid and alkali resistance and salt tolerance of cya mutant were significantly lower than the parent strain;the composition testing revealed that the cya mutant did not produce cellulose,curli and biofilm;at the same time the adhesion and invasion to epithelial cells of cya mutant had a prominent depression,and the toxicity to HeLa cells was weaker than the parent strain.Conclusion:The function of cya gene is closely related to athletic ability, penetration of cell membrane, the formation biofilm and virulence.It will provide a theory reference to the functional research of Salmonella typhimurium cya gene and the mechanism of attenuated strain.This will contribute to the development of oral vaccine using attenuated Salmonella typhimurium as vector.

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-kB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-kB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-kB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-kB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-kB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-kB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

Objective:In order to develop a safer vaccine strain exploit Salmonella typhimurium vaccine strain .A ΔsipB mutant of Salmonella typhimurium SL 1344 strain was constructed.Methods: Firstly, the recombinant suicide plasmid containing the missing 585 bp sipB ( PREΔsipB ) was built by homologous recombination , and screenned by two-step method.Results: PCR and sequencing results showed that SL 1344ΔsipB was successfully constructed.It was no significant changes compared with SL 1344.But compared with the parent strains SL 1344 , the mutant strain had obvious change in its virulence , oral challenge of bacteria in mice revealed that LD50 of the mutant strain was 1.70 ×108 CFU,the toxicity reduced about 1.4%.The protection rate induced by the sipB mutant was 50%,and the serum antibody peaked 14 d post-immunization.Conclusion:The SL1344ΔsipB mutant was constructed suc-cessfully,and genetic stability ,significantly reduced virulence.The study provides a new approach for further study of the relationship between the gene and pathogenicity of Salmonella typhimurium.It is likely that the ΔsipB mutant could be adapted to develope attenuated Salmonella vaccine.

Objective To evaluate the effect of urapidil on myocardial reperfusion and cardiac function during primary percutenons coronary intervention (PCI) in acute myocardial infarction (AMI) patients.Methods 54 AMI patients undergoing primary PCI were randomized to intracoronary urapidil (n=27) and nitroglycerin (n=27) group.When blood flow grade TIMI-l or more appeared in the infarct related artery (IRA) before or after percutenous transluminal coronary angioplasty (PTCA),urapidil (12.5 mg) or nitroglycerin (0.2 mg) was given intracoronary and then stents were implanted as needed.TIMI blood flow,no reflow/slow floW,corrected TIMl frame count (cTFC),myocardial blush grade (MBG),ST resolution (STR) on ECG, peak of creatine kinase (CK),cardiac troponin T (cTnT) were observed before and after PCI.Left ventricular ejection fraction (LVEF) was measured 24 hours and 30 days after PCI and MACE including death,reinfartion,revascularization in hospital were observed. Resuits Urapidil group compared to the nitroglycerin group,cTFC (18.38±3.30 vs.21.44±4.26,P=0.005) decreased and MBG (P=0.040) improved.STR in the urapidil group improved significantly compred to the nitroglycerin group (93% vs.70%,P=0.038).LVEF of 24 hours and 30 days after PCI in the urapidil group was higher than that ofthe nitroglycerin group (0.55±0.05 vs.0.52±0.06,P=0.021 and 0.58±0.06 vs 0.54±0.06,P=O.041,respectively).Peak CK (1895.26±1239.02 vs.1269.96±515.84,P=0.021) and peak TnT (5.81±5.27 vs 3.64±2.35,P=0.050) in the urapidil group decreased more significantly than that of the nitroglycerin group.No difference of MACE was found in the two groups.Conclusion Intracoronary urapidil administration adjunct to primary PCI in AMI ameliorates coronary blood flow and myocardial perfusion, improves ventricular function,and reduce the infarct size and does not incllase the incidence of complications during hospitalization.

Objective: To develop an oral live vaccine vector which stably carries exogenous genes.Methods:SL1344ΔsipBΔasd host-vector balanced lethal system was constructed by the method of recombinant suicide plasmid-mediated allelic exchange on the basis of attenuated Salmonella typhinurium SL1344ΔsipB.Then,the biological characteristics of SL1344ΔsipBΔasd was analyzed.Results:The results showed that the mutant was stabile with the Δasd gene in vitro;the serotype and growth rate of SL1344ΔsipBΔasd strain was almost same as the parent SL1344ΔsipB and SL1344 strain.And the mutant strains remain swim ming zones.Virulence test in mice showed that the virulence of SL1344ΔsipBΔasd which carried complementary plasmid pYA3493 by electro-transformation decreased by 1.4%compared with SL1344.Conclusion: These results showed that the SL1344ΔsipBΔasd mutant was successfully constructed.It is likely that this mutant should be used as a live vector to express foreign genes.