Objective To probe into the effect of sitagliptin on blood glucose fluctuation of the patients with type 2 diabetes mellitus(T2DM) and poor control by insulin aspart 30.Methods Ninety cases of T2DM and poor control by insulin aspart 30 in affiliated Zhongshan hospital from January 1,2014 to December 31,2014 were selected and randomly divided into three groups:simply continuous subcutaneous insulin injection(CSII),acarbose combined CSII group(CSII + Aca) and sitagliptincombined CSII group (CSII + Sig),30 cases in each group.Three groups received the intensive treatment for 2 weeks,and72-h continuous glucose monitoring was performed on last 3 d.The 24 h mean blood glucose(24 hMBG),largest amplitude of glycemic fluctuation(LAGE),mean amplitude of glycemic excursion(MAGE) within 1 d,postprandial blood glucose spike(PGS),postprandial glucose peak time(△t),postprandial glucose excursion(PPGE) and total T were observed within 24 h.The difference of insulin dose(△ insulin),hypoglycemia incidence,glucose-target rate,blood glucose profiles were compared at the end of treatment.Results After two-week treatment,intraday blood glucose variation indicators(24 hMBG,LAGE and MAGE) and postprandial blood glucose variation indicators (PGS,△t,PPGE and total T) in the CSII+Sig and CSII+-Aca groups were significantly lower than those in the CSII group(P＜ 0.05),while the differences in blood glucose variation indicators between the CSII+Sig group and CSII+-Aca group were not statistical significant(P＞ 0.05).In the comparison after treatment,△ insulin,hypoglycemia incidence and glucose-target rate in the CSI + Sig group were lower(P＜0.05).Conclusion The combined application of short-term CSII and sitagliptin will achieve a better effect than the combination with acarbose,can smoothly and steadily reduces the blood glucose level,relieves the whole day glucose fluctuations,effectively reduces △ insulin,and has lower hypoglycemia occurrence rate.

Objective To establish a stable cell line secreting human IgE Cε2-4 protein, and in-vestigate the binding capacity of receptor FcεR Ⅰ Methods The E24 gene was derived from SKO-O07 cell line, and was then cloned into pcDNA3.1 (+) (signal peptides were synthesized and fused at the 5'-end of E24 gene) or pCMV-L vector. After transient transfection into 293T cell, the secreted F24 protein was ana-lyzed by sandwich ELISA. The best vector was chosen to be transfected into CHO cells with LipofectAMI-NETM 2000 reagent. After being selected by G418 and subcloned three times by limited-dilution method, two stable cell lines were established. E24 gene was amplified by RT-PCR, and the E24 protein in the superna-tant was identified by ELISA. Besides, the binding capacity of FceR ⅠⅡ was analyzed by flow cytometry method. Results Three mammalian expression vector SP-E24-F3. 1, SP lI-E24-P3.1 and E24-PL were constructed and transient transfected to 293T cells. The output of E24 protein in the supernatant were 19.1, 19.4 and 8.7 μg/ml, respectively. Then the vector SP IX-E24-P3.1 was transfected into CHO cells. Final-ly, two single clones secreting E24 protein were stably obtained. The output of E24 were all at least 25 μg/ml. RT-PCR could detect the E24 gene from one of the two clones. Furthermore, flow cytometry results showed that E24 could bind the receptor in a dose-dependent manner. Conclusion Two stable cell line se- creting E24 protein were obtained, while E24 could specifically bind FcεR Ⅰ.

Objective:To explore the torque effect of controlling root auxiliary arch on the straight wire appliance on maxillary anterior teeth.Methods:22 patients with class Ⅱ1 extraction treatment,treated with straightwire appliance,at the detailing treatment stage were treated with controlling root auxiliary arch over the erect or introverted maxillary incisors for positive torque.The main arch wire of 0.46 mm ×0.64 mm stainless steel edge wire was used in 14 cases,the main arch wire of 0.46 mm stainless steel round wire was used in 8 cases.Cephalometric results before and after maxillary incisor torque were analyzed by t test.Results:After maxillary incisor torque in the 22 cases 1-SN and UIa-NA value increased(P ＜0.01),positive torque was achieved by controlling root auxiliary arch on the upper incisors;the round wire maxillary incisor torque worked faster than the edge wire(P ＜0.05).Conclusion:At the detailing stage of treatment straight wire appliance on front teeth,controlling root auxiliary arch is simple and effective in the treatment of exces-sive erect or lingual inclination of maxillary incisor.

Objective:To assess the guidance of 3D reconstruction in the surgical and orthodontic management of maxillary palatal impacted canines with cone-beam computed tomography (CBCT).Methods:22 adolescent patients with 26 impacted maxillary conines were examined by CBCT.CBCT 3D reconstruction was used to observe the impaction of the canines.Measurements were taken to evaluate spatial relationship between the canine and adjacent structures and resorption of neighboring incisor roots.Results:CBCT was effective to localize the impacted canines.All of the maxillary palatal impacted canines inclinated mesially,angles of impacted ca-nines to occlusal plane were 61.1°±18.1°,there were 8,5,3 and 10 impacted canines found in classⅠ,Ⅱ,Ⅲ and Ⅳ mesial mal-position respectively.3 adjacent lateral incisors and 2 central incisors were extracted because of severely root resorption.Normal occlu-sion was achieved for 26 impacted canines by the traction of the canines into dental arch and reaching the occlusal plane.Conclusion:CBCT can spatially show the palatal impaction of maxillary canines and the relationship to adjacent tooth,can guide the treatment plan and traction direction,therefore increase therapeutic effect.

Objective Ticagrelor-related dyspnea may affect the medication adherence of patients with coronary artery disease.This study aims to assess the impact of ticagrelor adherence on 1-year cardiovascular outcomes in pateints with stable coronary artery diseases (SCAD).Methods This study includes the patients with SCAD from Fuwai hospital who discharged with ticagrelor between Jan.2015 to Jun.2015.We collected data of clinical characteristics and ticagrelor adherence from these patients by reviewing the electronic medical records and personnel interview.Follow-up was performed at 6 and 12 months by telephone interview or office visits.Results A total of 155 patients with SCAD were enrolled,of whom 122 (78.7％) were males with a mean age (57.0 ± 10.0) years.Among them,50 (32.3％) patients have a history of myocardial infraction and 106 (68.4％) patients had angiographic confirmed left main and/or multivessel disease.Forty-six patients (29.7％) with SCAD prematurely stopped ticagrelor within 12 months,while 25 (16.1％) patients switched from ticagrelor to clopidogrel.Hemorrhagic events and locally unavailable ticagrelor were the major reasons causes of the premature discontinuation of ticagrelor.Univariate analysis showed age,body mass index (BMI),hypertention and locally unavailable ticagrelor as relative factors for early ticagrelor discontinuation after discharge.Multivariate analysis revealed unavailable drug locally (OR 0.25,95％ CI 0.09-0.69) and elderly patients (OR 4.13,95％ CI 1.40-12.19) were risk factors for low persientence or premature ticagrelor discontinuation.Conclusion This study showed poor ticagrelor adherence in patients with SCAD after discharge.Locally unavailable ticagrelor and elderly patients were strong predictors of poor ticagrelor adherence.Discontinuation to ticagrelor prematurely may not have impact on adverse cardiovascular outcomes.

Objective: To explore the impact of knocking out wildtype p53 phosphatase 1 gene on heart function with the changes of cardiac tissue mRNA and protein expressions in experimental mice. Methods: Our research included in 2 groups: Wildtype (WT) mice group and Wip1 knockout (Wip1-KO) mice group. n=10 in each group. The heart function, ratio of heart weight to body weight (HW/BW) were examined and compared between 2 groups; cardiac tissue morphology was observed by HE staining; mRNA expressions of ANP, BNP, MCP-1 andα-SMA were determined by RT-PCR and protein expressions of Bcl-2, Bax and c-caspase3 were measured by Western blot analysis. Results: Compared with WT mice group, Wip1-KO mice group showed decreased Wip1 mRNA expression,P<0.05, decreased LVEF, LV fraction shortening and increased left ventricular end systolic diameter (LVESD), allP<0.05; Wip1-KO mice group had reduced BW and elevated ratio of HW/BW, bothP<0.05 even the heart weight was similar between 2 groups. There was no difference in cardiac tissue morphology between 2 groups; mRNA expressions of ANP, BNP, MCP-1 and α-SMA were similar between 2 groups,P>0.05; apoptosis related protein expressions of Bax/Bcl-2 and c-caspase3 were similar between 2 groups,P>0.05. Conclusion: Wip1 gene knockout may impair the heart function in experimental mice, while the relevant mechanism should be further investigated.

Objective To explore the relationship between optical coherence tomography (OCT) characteristics and peripheral blood leukocyte count in patients with acute myocardial infarction(AMI). Methods A total of 33 patients with AMI hospitalized in Fuwai Hospital for primary percutaneous coronary intervention were consecutively enrolled,and underwent intracoronary OCT procedures after manual aspiration of coronary thrombus. Demographic data, risk factors, procedural and OCT data, past medical history and perioperative laboratory findings were collected in all patients. Results The lymphocyte count,monocyte count and basophil count were significantly higher in the patients with fibrous cap thickness ≥ 65 μm than in those patients with fibrous cap thickness ≤ 65 μm. Patients presenting with cholesterol crystallization had lower eosinophil count than those patients with crystallization-free [(0.04±0.06)×109/L vs.(0.10±0.09) ×109/L,P =0.028]. In addition,the former had significantly higher to neutrophil lymphocyte ratio than the latter [(8.35±6.13)vs.(4.97±2.01), P =0.020]. Higher monocyte count was found in the patients with calcified plaque (P <0.05). Platelet to lymphocyte ratio was significantly increased in the patients with macrophage infiltration [(165.72±85.93)vs.(113.47±19.13),P <0.05]. The leukocyte count,neutrophil count and monocyte count showed the treat of elevation as the number of OCT characteristics increased,but only the elevation of monocyte count had statistical significant level (P = 0.014). Conclusions Peripheral blood leukocyte count seems to be associated with OCT characteristics of plaque rupture in patients with acute myocardial infarction,suggesting the potential role of inflammation in plaque rupture.

Objective To evaluate the safety,effectiveness and clinical factors of re-intervention of transjugular intrahepatic porto-systemic shunt (TIPS).Methods A retrospective study of safety and longterm outcomes of TIPS was made in 771 patients from August 1994 to August 2010.The 625 patients had follow-up data.The patients who received TIPS once,twice,and more than twice were divided into group 1,group 2 and group 3,respectively.Clinical symptoms,survival rate and restenosis rate of each group were analyzed.Clinical influencing factors of re-intervention effect were discussed.Results The success rate of first intervention was 98.2％ (757/771),the death rate was 0.7％ (5/757) and severe complication rate was 2.5％ (19/757).The success rate of re-intervention was 98.7％ (457/463),no death and severe complications occurred.The restenosis rate in group 3 decreased significantly than group 1 ( x2 =7.908,P ＜0.05 ) in the first year of TIPS.The restenosis rates in group 2 and group 3 were lower than group 1 from 2 to 5 years of TIPS ( x2 values were 27.046,25.724,37.002 and 19.046,respectively,P ＜ 0.05 ). The survival rate in group 3 was higher than group 1 (x2 =9.114,P＜0.05)and group 2 was higher than group 1 ( x2 =4.929,P ＜ 0.05 ) in the first year of TIPS,while there was no statistical difference between group 2 and group 3 ( x2 =2.678,P ＞ 0.05).The patients in group 2 and group 3 also had higher survival rates than group 1 from 2 to 5 years of TIPS (x2 value were 41.314,26.920,13.692 and 6.713,respectively,P ＜ 0.05 ).19.4％ (79/406)of patients who received re-intervention had symptom recurrence and shunt stenosis or occlusion. 11.6％ (47/406) of patients had symptom recurrence with portal hypertension signs,62.8％ (255/406) had shunt stenosis or occlusion with portal hypertension signs.Conclusions Restenosis or occlusion of TIPS,symptom recurrence and portal hypertension signs were important factors for re-intervention.Re-intervention of TIPS was safe and effective,and could improve the survival rate of patients with TIPS.

Objective To examine whether Tim-3 plays a protective role in paraquat poisoning induced excessive immune response and tissue damage based on the critical roles of Tim-3 controlling inflammatory response.Methods A paraquat poisoning model was established in wild type and in Tim-3 transgenic C57BL/6 mice by intraperitoneal injection of paraquat (40 mg/kg) .In addition, C57BL/6 mice with paraquat poisoning were injected with Tim-3 soluble protein( sTim-3) or control protein to see the effect of Tim-3 blocking on the progression of paraquat poisoning.Samples were collected at 6 and 24 h after paraquat injection respectively and were examined for tissue damage, cytokine expression and paraquat metabolism.Results After paraquat poisoning, there was significantly attenuated tissue damage in the lungs and kidneys and decreased TNF-α,IL-6 and IL-1 beta expression in the PBMCs or in the serum from Tim-3 transgenic mice compared to wild type mice.The serum concentration of paraquat in Tim-3 transgenic mice was also significantly decreased.However, in sTim-3 treated paraquat poisoning mice, there was significantly increased cytokine expression and tissue damage compared to control protein treated mice.The in vitro data showed that Tim-3 signaling negatively regulated macrophages mediated inflammatory response.Conclusion Tim-3 plays a critical role in maintaining the homeostasis after paraquat poisoning. Further investigation on the regulatory roles of Tim-3 in inflammation will shed new light on the pathogenesis of paraquat poisoning and provide new therapeutic strategies.

Objective To study the intrinsic relationships between the binding energy of the antibody light and heavy chains and the conformational characteristics , physical and chemical properties , and to establish a corresponding mathemat-ical model and evaluate the thermal stability of the antibody molecules , which contribute to the antibody design , optimiza-tion and affinity maturation .Methods Based on bioinformatics and computational biology methods , the antibody′s structur-al information with the crystal diffraction data was analyzed .The conformational character of the variable domain of the antibody was studied using distance geometry and computer graphics technology .With the aid of the intermolecular hydrogen bond formation theory and the reaction free energy theory , the dynamic structure and energy characteristics be-tween the heavy and light chain variable regions of the antibody were studied .Furthermore , using nonlinear fitting and regression analysis, a mathematical model was set up .Results According to simulation and statistic analysis , there was a linear relationship between the binding energy and the number of the intermolecular hydrogen bonding , Van der Waals interaction of the heavy and light chains of the antibody .There was polynomial correlation between the binding energy and the physicochemical properties of the antibody .Using the frequency of amino acid position and the established model , the humanized anti-ricin antibody , which could not obtain the stable engineering cell line , was evaluated and optimized .The stable engineering cell line of the humanized anti-ricin antibody was obtained in the experiment .Conclusion The self structure of the antibody variable region ( conformation and physicochemical properties ) has much effect on its stability . The antibody stability can be improved by structural optimization .