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

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

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.

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.

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 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.

Objective To analyze the application of recombinant VCA-BALF4(S) and VCA-BFRF3 proteins in serological diagnosis of nasopharyngeal carcinoma (NPC). Methods DNA extracted from the B95-8 cells was used as the templates in a polymerase chain reaction(PCR). VCA-BALF4 1008 bp (S) (aa 287-623) and VCA-BFRF3 531 bp(177 as) were generated and inserted into pPICZaA vector.The recombinant plasmids were transformed into GS115 yeast by electroporation. The yeast transformants in-duced by methanol expressed recombinant proteins. The recombinant proteins synthesized were coated to mi-croplate for detection of EBV-IgA antibody in NPC patients by ELISA. Results We have successfully se-cretly expressed the recombinant VCA-BALF4(S) and VCA-BFRF3 protein in the Pichia pastoris. The mo-lecular weight of products were approximately 37×10~3 and 18×10~3, respectively. The recombinant proteins VCA-BALF4(S) and VCA-BFRF3 in the culture supematant showed good immunoreactivity with IgA anti-bodies to EBV by Western blot. A novel ELISA was established using Pichia pastoris-expressed VCA-BALF4 (S) and VCA-BFRF3 proteins. Serum samples were collected from patients with NPC and healthy controls and using this ELISA tested. The sensitivity of VCA-BALF4(S) and VCA-BFRF3 tests in the NPC sera were 88.7% and 71.0%, whereas the specificity of normal individuals are 96.4% and 91.8% separately. Con-clusion The recombinant proteins BALF4 (S) and BFRF3 were highly secretly expressed in Pichia pastoris,the diagnostic value of two recombinant proteins in screening for NPC patients were primary evaluated and the valuable pPICZa-BALF4(S) yeast strain was obtained.

AIM: To study the expression of hepatitis B virus core gene in Pichia pastoris and to obtain high-level expressed recombinant HBcAg with good immunoreactivity and high specificity. METHODS: HBV core gene was amplified by PCR from plasmid pHBV1 which contained HBV whole DNA sequence. The PCR product was cloned into pGEM-T vector by TA cloning strategy. After confirmed by DNA sequence analysis, the gene of interest was inserted into the yeast expression vector pPIC9. The recombinant plasmid pPIC9-cAg was constructed and transformed into GS115 by electroporation. The recombinant yeast GS115 was induced by 0.5% methanol. The expressed product was analysed by SDS-PAGE,Western blot and ELISA. RESULTS: The restriction analysis and DNA sequence analysis proved that HBV core gene had already been cloned to yeast expression plasmid pPIC9. The expressed HBcAg existed in SDS-PAGE. Good immunoreactivity and high specificity of the recombinant HBcAg have been proved by ELISA and Western blot. The titre of the recombinant HBcAg in the cell lysate was 1∶ 12 800 . CONCLUSION: The recombinant plasmid pPIC9-cAg was successfully constructed. The recombinant HBcAg with good immunoreactivity and high specificity was successfully expressed in Pichia pastoris expression system and can be applied to further developing HBcAb immunoassay. [

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.

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