Arterial Occlusive Diseases ; diagnosis ; etiology ; Coronary Disease ; complications ; diagnosis ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged

Objective To establish a suitable animal model of experimental periodontitis and study the relationship between stress and inflammatory periodontal diseases.Methods Forty Wistar rats with nylon thread placed around the neck of maxillary left second molar tooth were divided randomly into two groups:stress group(the rats were treated with restraint strees for 12 h every day for 10 d)and control group.Four rats of either group were sacrificed at the day of 2,4,6,8,10,separately;the level of blood glucose and the contents of adrenocorticotropic hormone(ACTH),orticosterone and adrenaline were measured as the stress markers,as well as the relative weight of the thymus and spleen.The furcation area of the second maxillary molar was examined histologically and histometrically.Results In stress group,all the markers for stress were significant higher than those in control group,and the thymus and spleen were atrophied(P

Objective To study the clinical effect of Shenkang injection combined with valsartan in the treat-ment of patients with early stage diabetic nephropathy,and its influence on the expression changes of homocysteine ( Hcy) ,transforming growth factor β1 ( TGF -β1 ) , the inflammatory cytokines high sensitive C -reactive protein (hs-CRP),and interleukin-6 (IL-6).Methods 138 cases of early stage diabetic nephropathy were randomly divided into control group ( conventional treatment, valsartan act as antihypertensive drug ) and treatment group ( treated with Shenkang injection combined with valsartan) by digital table.The total effective rate,glycemic index, renal function,levels of Hcy and TGF-β1,expression levels of inflammatory cytokines of two groups were compared. Results The total effective rate of the treatment group (91.30%) was significantly higher than the control group (76.81%) (χ2 =5.004,P<0.05).The values of FPG,2h PG,HbAlc,UAER,CysC and Scr were lower in the treat-ment group compared with the control group (t=4.514,3.743,4.754,6.214,3.925,3.777,all P<0.05).Com-pared with the control group,the concentrations of Hcy,TGF-β1,hs-CRP and IL-6 decreased significantly[ (11. 78 ±1.95)μmol/L vs (9.21 ±1.64)μmol/L,(71.32 ±14.88) mg/L vs (60.04 ±11.75) mg/L,(7.07 ±1.25) mg/L vs (5.81 ±1.14)mg/L,(50.24 ±21.86)pg/mL vs (32.55 ±17.01)pg/mL],the differences were statistical-ly significant (t=8.378,4.942,6.187,5.305,all P<0.05).Conclusion Shenkang injection combined with val-sartan for the treatment of early stage diabetic nephropathy has significant clinical efficacy.It can improve patients're-nal function and reduce blood sugar levels.The effects may be related with inflammatory response inhibition and Hcy, TGF-β1 levels reduction.

Hepatic artery stricture (HAS) after liver transplantation can lead directly to transplanted liver function exhaustion and complications of biliary system. The early diagnosis and treatment are crucial for better prognosis. Doppler ultrasound is the first method of choice, and angiography can give further clear dignosis. The balloon dilatation is still effective for hepatic arterial stenosis. With the more adaptable usage of oronary stent, if possible, would reveal more promising result especially for tortuous stenotic hepatic artery. The vascular reconstruction or repeated liver transplantation is still the effective therapeutic methods.

Objective To investigate the complications of different enteral nutrition in patients after surgery for massive cerebellar infarction,so as to guide rational application of enteral nutrition in patients.Methods Forty-nine patients with massive cerebellar infarction were divided into three groups randomly:conventional nasogastric tube feeding group (group A,n =12),nasogastric tube feeding plus gastric motor drug group (group B,n =18),and nasojejunal tube feeding group (group C,n =19).The incidences of diarrhea,reflux,aspiration,upper gastrointestinal bleeding and aspiration pneumonia within 3 weeks after initiation of enteral nutrition were observed and compared among the groups.Results The incidence of diarrhea showed no statistically significant difference among the 3 groups (x2 =0.092,P =0.955).Compared with group A,the incidences of reflux,aspiration and aspirafion pneumonia were significantly lower in group B and group C (P ＜ 0.05),and lower in group C compared with group B (P ＜ 0.05).Compared with group C,the incidence of upper gastrointestinal bleeding was significantly lower in group C than in group A and group B (x22 =4.748,P2 =0.029;x23 =4.284,P3 =0.038),but the difference between group A and group B was not significant (x21 =0.000,P1 =1.000).Conclusions Because of the unique pathophysiological features in patients after surgery for massive cerebellar infarction,early enteral nutrition by conventional nasogastric tube feeding may be inappropriate.Nasogastric tube feeding plus gastric motor drug may be applied in mild case with short course of disease.Nasojejunal tube feeding may be the approach of choice for enteral nutrition in critical patients with massive cerebellar infarction for its association with lower incidence of complications.

Objective To explore the differences in clinical features between the latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM) in the elderly.Methods Clinical features of 41 cases with LADA and 49 cases with T2DM were retrospectively analyzed and compared.Results (1) Body mass index (BMI),fasting and postprandial levels of cpeptide,triglyceride (TG) and serum albumin were lower in LADA patients than in T2DM patients.(2) The levels of fasting and postprandial blood glucose were higher in LADA patients than in T2DM patients.(3) There were no statistically significant differences in the disease course,blood pressure (BP),and the functions of liver and kidney between LADA and T2DM patients.Conclusions As compared with T2DM patients,LADA patients have higher blood glucose level,lower BMI and TG level,and poorer function of islet B cell.But there is no significant difference in the chronic complications between two groups.

Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; therapeutic use ; Antiviral Agents ; chemical synthesis ; chemistry ; therapeutic use ; Drug Discovery ; Drug Resistance ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Hepatitis C ; drug therapy ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; Protein Binding ; Protein Kinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Serine Proteinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use

Objective:To prepare superparamagnetic iron oxide(SPIO) nanoparticles and to observe its acute toxicity on mice,so as to pave a way for further study on its long-term toxicity and on its role as a carrier in magnetic resonance gene imaging.Methods: The SPIO nanoparticle was obtained by means of co-precipitation,and its physical and chemical parameters were determined by transmission electron microscope,atomic force microscope,and 1.5 T super conduct MR,etc.According to the administration pathway and doses of SPIO,90 mice were divided into oral administration(with a total dose of 2 104.8 mg/kg and a volume of 40 ml/kg,n=30),intravenous injection(a total dose of 438.5 mg/kg and a volume of 25 ml/kg,n=30) and intraperitoneal injection(with a total dose 1 578.6 mg/kg and a volume of 30 ml/kg,n=30) groups.Another 10 mice in each group receiving the same dose of normal saline via the same pathway served as the controls(n=10).The general condition,the major serologic parameters,and the pathological changes of major organs were observed 14 d after administration in each group.Results: We have successfully prepared SPIO,and its core component was Fe3O4 crystal,with a size of 20-35 nm,a T2 relaxivity of 0.155?106 mol-1?sec-1,a specific saturated magnetization of 68.395 68 emu/g,and a retentivity of 21.463 74 Gs.There was no death of mice during the observation.There was no significant difference in serological parameters between mice of different groups and between each experiment group and their corresponding control group.No edema,degeneration and necrosis were seen in the liver,spleen,kidney,heart,and lungs by H-E staining and marrow by Wright staining;only a few blue particles were observed in the liver and spleen in the administration groups by Prussian blue staining,none observed in the control groups.Conclusion: SPIO prepared in the present study meets the requirement of MR imaging,with no acute toxicity to mice,and warrants further study for future MR gene imaging.

Background Establising the culture model of Müller cells for obtaining the highly putified target cells is essential for the study about the physiology and pathology of retinal Müller cells. The exsiting purifing method for culturing Müller cells is dissatisfactory. Objective This study was to establish a method to obtain high purifing Müller cells. Methods The retina from 5 clean newborn SD rats were isolated and digested by 0. 01% trypsin and cultured in DMEM containing 10% fetal bovine serum. The cellular suspension was then prepared,and the target cells were screened using flow cytometry based on the size and the quantity of cells. Cultured and passaged cells were identified by transmission electron microscope and light microscope. Immunocytochemistry was used to detecte the expression of GFAP in cultured cells for the determination of type and purity of the cells. Results The cells showed the similar shape to retinal Müller cells after primarily culture with the large volume, and some small other types of cells could been seen. The growth of cells was quickly 3 weeks later. The fibroblasts were removed using sticking-wall by steps,and neurons were eliminated following passage. Aboundent of cellular organs were seen under the transmission electron microscope. The positive response rate of the cells for CFAP was 100%. Conclution Flow cytometry offer a rapid and feasible approach for purifying Muller cell and it builds the foundation for further study about Müller cells.

Objective To explore the mechanism of insulin resistance regulated by fibroblast growth factor 21 (FGF21)and identify its role in oxidative stress.Methods High-fat diet-induced obese mice were treated with FGF21 ,and hepatic oxidative stress markers such as iNOS and insulin signaling molecules such as IRS-1 and Akt were assessed by Western blot and co-immunoprecipitation.Meanwhile,liver steatosis was assessed in liver sections stained with oil red O.Results Obese mice in FGF21 group showed reduced body weight,blood glucose and serum insulin levels,and improved insulin sensitivity as measured by glucose tolerance testing (GTT)and insulin tolerance testing (ITT)compared with obese mice in vehicle group.Meanwhile,FGF21 treatment in obese mice decreased protein expressions of iNOS and TNF-α,and increased insulin-stimulated IRS-1 tyrosine phosphorylation and Akt Ser-473 phosphorylation,indicating that FGF21 inhibited hepatic oxidative stress and restored impaired insulin signaling.Additionally,we found significantly reduced lipid accumulation in liver sections stained with oil red O in FGF21-treated obese mice.Conclusion Our results support the notion that FGF21 is an important regulator of insulin resistance and that FGF21 may reduce lipid accumulation in the liver,restore hepatic insulin signaling and improve insulin sensitivity in obese mice,at least in part,by inhibiting hepatic oxidative stress.Therefore,FGF21 has a potential value in clinical application.