AIM: To observe the anti-apoptosis effect of liraglutide on the islet through microRNA-375 (miR-375) for providing additional pharmacodynamic evidence for its clinical application.METHODS: For in vivo study, C57BL/KsJ-db/m mice aged 8 weeks served as normal control group.A total of 40 male genetically diabetic C57BL/KsJ-db/db mice at the same age were randomly divided into diabetic control group (the db/db mice were injected subcutaneous-ly with equivalent amount of saline) and liraglutide group (the db/db mice were injected subcutaneously with liraglutide at dose of 300 μg? kg-1? d-1 ).After 8 weeks of administration, body weight (BW) was measured and blood was collected for detection of fasting blood glucose (FBG), fasting blood insulin (FINS), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).Before sacrifice, intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were conducted.The histopathological features in the islet tissue were examined with HE staining.The apoptosis in the islet tissue was detected by TUNEL staining.The protein levels of caspase-3, Bcl-2 and Bax were deter-mined by Western blot.The level of miR-375 in the islet tissue was detected by qPCR.For in vitro study, the MIN-6 cells were cultured and divided into control group (incubated with equivalent amount of solvent), miR-375 mimic group and miR-375 mimic +liraglutide group.The cell viability was examined by MTT assay.The protein levels of caspase-3, Bcl-2
and Bax were detected by Western blot.RESULTS: In the in vivo study, compared with control group, the levels of BW, FBG, FINS, TC, TG and LDL-C were decreased significantly in liraglutide group.The islet apoptosis was reduced by the administration of liraglutide.The expression of Bcl-2 was up-regulated significantly, while the protein levels of caspase-3 and Bax were down-regulated significantly in liraglutide group.The level of miR-375 was decreased significantly.In the in vitro study, the cell viability was decreased in miR-375 mimic group and increased in miR-375 mimic +liraglutide group. Moreover, the expression of Bcl-2 was decreased and the protein levels of caspase-3 and Bax were increased with the incu-bation of miR-375 mimic, while the expression of Bcl-2 was increased and the protein levels of caspase-3 and Bax were de-creased with the co-incubation of miR-375 mimic and liraglutide.CONCLUSION: Liraglutide attenuates islet apotosis, and the mechanism may be associated with its effects of reducing the elevated level of miR-375 in islet tissues.

AIM: To observe the therapeutical effects of resveratrol on non-alcoholic fatty liver disease and its potential mechanism.METHODS: Male C57BL/6J mice were fed with high-fat and high-cholesterol diet to established non alcoholic fatty liver disease model, and were administrated with resveratrol at doses of 80 mg/kg and 160 mg/kg.After 4-week treatment, the blood sample was collected for determination of total cholesterol (TC) and triglyceride (TG).The liver tissues were harvested for measuring the liver lipid content.The histopathological examination were conducted with hematoxylin and eosin staining.The ceramide levels in the liver tissues were detected by HPLC-MS.The microRNA (mi-RNA)-122 levels in the liver tissues were detected by real-time PCR.The protein levels of serine palmitoyltransferase (SPT) were determined by Western blot.The HepG2 cells were cultured and divided into 5 groups: control group, model group (induced by 0.25 mmol/L oleic acid), model+resveratrol group (treated with 5 μmol/L resveratrol), miRNA-122 siRNA group and resveratrol+miRNA-122 siRNA group.Except control group, the cells in other groups were stimulated with oleic acid and incubated with respective drugs simultaneously for 24 h.The levels of TC, TG and ceramide in the cells of each group were measured.The protein levels of SPT in each group were determined by Western blot.RESULTS: In non-alcoholic fatty liver disease mice, resveratrol dose-dependently reduced the serum TC and TG levels, decreased the lipid deposition, the ceramide level and the SPT protein level, and increased the level of miRNA-122 in the liver tissues.In the in vitro study, compared with model group, resveratrol reduced the serum TC and TG levels, decreased the ceramide level, reduced the SPT protein level.Compared with control group, the levels of TC, TG and ceramide, and the protein expression of SPT were increased in miRNA-122 siRNA group.Compared with miRNA-122 siRNA group, no statistical difference of TC, TG, ceramide and protein expression of SPT in resveratrol combined miRNA-122 siRNA group was observed.CONCLUSION: Resveratrol significantly reduces lipid accumulation by reduction of miRNA-122 and ceramide levels, and decrease in SPT protein levels in the liver.

OBJECTIVE:To study the consistency policies of generic drugs in China,America and Japan comparatively,and provide reference for perfecting quality and efficacy consistency evaluation of generic drugs in China. METHODS:Generic drugConsistency evaluationQuality evaluationDESIwere used as keywords to search the related literatures or information of ge-neric drugs published or reported in CNKI,Web of Science,Elsevier,Springer database and USA FDA website during Jan. 1st, 1950-Jun. 30th,2016. And comparative analysis was conducted for the historical background,evaluation methods and policy influ-ences of consistency policies of generic drugs in China,America and Japan. RESULTS:There were differences in the historical background,evaluation methods,major participants and policy influences of consistency policies of generic drugs in China,Ameri-ca and Japan. The evaluation for generic drugs in USA was reevaluation of the drugs effectiveness under the history of drug registra-tion regulation was imperfect. With experts'review,it was evaluated based on FDA,enterprises,scientific literature evidence and experts review. Main evaluation method was in vitro dissolution test in Japan. The consistency evaluation of generic drug in China focused on the generic drug marketing authorization,mainly using in vivo bioequivalence. And the standards of reference prepara-tions were from the basically similar drugs to the original drugs. CONCLUSIONS:Compared with innovation-based countries like America and Japan,the availability of reference preparations in China is low,and policy environment is more complex. China should further improve the laws and regulations,giving reasonable buffer period,considering the diversity of evaluation methods, exemptions in special circumstances and current situation of pharmaceutical industry,paying attention to the balance between techni-cal supervision and system supervision.

Human FceR I a subunit extracellular domain was cloned and expressed with 2 different expressing systems and Dot blot was used to detect its biological activity to bind with IgE,providing reference for binding mechanism of human FceR I a subunit extracellular domain with IgE. It was shown that FceR I a subunit extracellular domain from pBAD/g I A expressing system could bind with IgE, but the one from PQE30 expressing system could not bind with IgE. It is suggested that FceR I a subunit extracellular domain alone is sufficient to bind with IgE without P and Y subunit. The proper space configuration and disulfide bond of FceR I a subunit is necessary for binding with IgE, but its glycosylation is unnecessary.

Objective To introduce experience of switch operation applied to treat the transposition of the great arteries(TGA) and Taussing-Bing deformity.Methods Between June,2000 and Aug,2002, 27 consecutive patients underwent an arterial switch operation at our institution. The patients including TGA with intact ventricular septum in 5, TGA with ventricular septal defect in 18, Taussing-Bing deformity in 3, and corrected TGA in 1.Age ranged from 3 days to 6 years at operation (mean, 10 1?5 7 months), and the mean body weight was 6 3?2 81kg. Twenty patients were older than age 1 month. Ninteen patients had pre-operative catheterization. Seventy-four percents had severe pulmonary hypertention. Two patients had left ventricular outlet stenosis. Coronary type A distribution was recognized in 23 cases,type D in 4, and one of them had the origin of the left descending artery tunneled in the aortic wall. The great arteries were side by side in 3 cases. One patient underwent balloon atrial septostomy and another one underwent pulmonary banding and systemic to pulmonary shunt preoperatively. The great arteries were transected above the valvular commisures,the coronary ostia with all the adjacent sinus of Valsalva were excised and re-implanted to the proximal neo-aorta,then aortic anastomosis was carried out.The proximal neo-pulmonary trunk was reconstructed with a large autologous native pericardium as a posterior patch.The pulmonary anastomosis was completed,after the aortic cross clamp was released.The VSDs were repaired through the atrium or proximal aorta with Dacron patches.Results The hospital mortality was 7 4% (2 cases), and no death cases were directly related to any coronary artery problem. One perioperative death was a 5 day-old neonate with TGA and an intact septum who had refractory hypotension, hypoxemia, and acidosis preoperatively who underwent an emergency operation. The patient had a refractory low cardiac output syndrome postoperatively, and died after 20 hours. Another patient had a chylothorax and died of allergy from iodophor 22 days postoperation. The pulmonary pressure had gone down significantly in 20 patients who had severe pulmonary hypertension preoperatively (the mean pressure 46.7mmHg preoperation, and 31.3mmHg postoperation). Follow-up of 1 to 26 months was achieved in all survivors, with no late complications and death. Conclusions The arterial switch procedure for age over 1 month infants with severe pulmonary hypertention still has satisfactory efficacy.

Objective: To explore the role of clinical pharmacists in the treatment of artial fibrillation complicated with digoxin poisoning and the entry points of pharmaceutical care.Methods: Clinical pharmacists participated in the therapy for a patient with atrial fibrillation and digoxin poisoning, monitored the blood concentration of digoxin combined with the characteristics of the patient, analyzed the causes of digoxin poisoning in terms of the underlying diseases, renal function and combined medication, and performed beneficial pharmaceutical care.Results: The suggestions of clinical pharmacists were adopted by doctors, digoxin was withdrawn timely and the drug poisoning was corrected.

AIM:To observe the effects of liraglutide on the level of microRNA-33 (miR-33) and the expres-sion of AMP-activated protein kinase ( AMPK ) and apoptosis-related proteins in mice with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism .METHODS:High-fat diet and intraperitoneal injection of streptozocin were used to establish the type 2 diabetic model in C57BL/6 mice.The mice were randomly divided into 4 groups ( n=15 ):in control group , the normal mice were subcutaneously injected with equivalent volume of saline ;in model group , the T2DM mice were subcutaneously injected with equivalent volume of saline ; in low-and high-dose liraglutide treatment groups, the T2DM mice were subcutaneously injected with 100 and 200 μg? kg -1? d-1, respectively.After 4 weeks of administration, the levels of FBG, TG, TC, HDL-C, LDL-C, ALT and AST were determined.HE staining was used to ob-serve the pathological changes of the liver tissues .The protein level of cleaved caspase-3 in the liver tissue was detected by the technique of immunofluorescence .The protein levels of p-AMPK/AMPK and apoptosis-related proteins were detected by Western blot .The expression of miR-33 in the liver tissues was detected by real-time PCR.RESULTS: Compared with model group, the contents of FBG, TG, TC, LDL-C, ALT and AST were decreased significantly , while the content of HDL-C was increased significantly in low-dose liraglutide group and high-dose liraglutide group ( P<0.05 ) .The protein levels of phosphorylated AMPK and Bcl-2 were up-regulated significantly , and the expression of cleaved caspase-3 was down-regulated significantly (P<0.05).The level of miR-33 was decreased significantly (P<0.01).CONCLUSION:Liraglutide alleviates liver injury in type 2 diabetic mice , and the mechanism may be associated with reducing the level of miR-33 and increasing the phosphorylation of AMPK in the liver tissues , thereby inhibiting hepatocyte apoptosis .

Objective To report a new minimally invasive and cosmetic approach for atrial septal defect repair. Methods 46 patients ranged 3.6 to 32 (12.5?7 7) years underwent minimal right vertical infra axillary thoracotomy for atrial septal defect repairs under beating hearts from January 1997 to March 2000. One had a functional single atrum,two had an associated partial anomalous pulmonary venous connection,and three had the moderate pulmonary hypertension. Results The average bypass time was (30 3?7 8) min. There was no operative or late mortality and no morbidity directly related to the thoracotomy with beating heart. 37 patients had been Followed up for 3 months to 2 4 years(1 3?0 6) years. All of patients were free of symptoms. Conclusions The minimal right vertical infra axillary thoracotomy is a safe,cosmetic and minimal invasive approach to median sternotomy for repair of atrial septal defect or anomalous pulmonary venous connection.

The development of equipment techniques of CT is comprehensively reviewed,including detectors, tube and data processing system. The clinical application of CT are analyzed. Several problems are put forward which must be dealt with urgently.

Objective To determine the surface expression of Fas Ag on RBL 2H3 and its function. Methods RT PCR and Western blot were used to detect the transfection and expression of Fas in RBL 2H3. Surface expression of Fas Ag was studied by immunochemistry. Apoptosis changes following treatment with anti Fas antibody were analyzed using flow cytometic analysis with annexinⅤ. Results It was successful in amplifying gene of rat Fas Ag, and a band of 32kD was detected by Western blot. The Fas Ag expression on the surface of RBL 2H3 by immunochemistry. RBL 2H3 exhibited apoptosis in response to anti Fas treatment. Conclusion Induction of rat mast cell apoptosis by activation of the Fas pathway provide the mechanism by which the number of mast cells may be regulated in the potential therapeutic strategy for anaphylactic diseases