High-risk human papillomavirus (HPV) is the principal cause of various cancers including cervical cancer, anal cancer, vulvar cancer, and some head and neck cancers. In the viral life cycle, by interacting with both viral and host DNA and proteins, the HPV E2 protein plays a pivotal role in viral transcriptional regulation and DNA replication, and it is also associated with modification of various cellular processes, including host gene transcription, RNA processing, apoptosis, ubiquitination, and intracellular trafficking, to create a convenient environment for a replicative cycle of the virus and contribute to the HPV pathogenesis. Elucidating the roles of E2 protein throughout the viral life cycle will improve our understanding of the viral life cycle and pathogenesis and help us identify novel antiviral agents with therapeutic potential. This article reviews the research progress in the structure, roles, and activity of high-risk HPV E2 protein, particularly that of HPV-16.
Animals ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Gene Expression Regulation, Viral ; Human papillomavirus 16 ; genetics ; metabolism ; Humans ; Oncogene Proteins, Viral ; genetics ; metabolism ; Papillomavirus Infections ; genetics ; metabolism ; virology ; Uterine Cervical Neoplasms ; genetics ; metabolism ; virology

Objective To study the relation of esophageal motility and acid reflux between gastroesophageal reflux disease (GERD) patients with and without esophageal injury.Methods A total of 25 patients who met the GERD diagnosis criteria were conducted esophageal-gastric-duodenal endoscopy examination and followed with high-resolution esophageal manometry.The changes of esophageal pH postprandial were also detected.The differences of esophageal motility and acid reflux time between GERD patients with and without esophageal injury were compared.Patients were divided into non-acid reflux group and acid reflux group according to DeMeester score.The changes of esophageal motility indexes of these two groups were compared.Wilcoxon test and t test were used for statistical analysis.Results There was no significant difference in baseline value of lower esophageal sphincter (LES) pressure,remained LES pressure,speed of the esophageal peristalsis,the time of esophageal pH＜4 and DeMeester score between groups with and without esophageal injury (all P＞0.05).But esophageal contraction amplitude of group with esophageal injury was lower than that of group without esophageal injury (31.9 mm Hg vs 64.2 mm Hg,1 mm Hg=0.133 kPa,Z=-2.37,P=0.02).There was no significant difference in baseline value of LES pressure,remained LES pressure,speed of the esophageal peristalsis between acid reflux group and non acid reflux group (all P＞0.05).But the esophageal contraction amplitude of acid reflux group was lower than that of non acid reflux group (36.4 mm Hg vs 71.8 mm Hg,Z=-2.25,P=0.02).Conclusions There was no significant correlation between the LES pressure and esophageal acid reflux with esophageal injury in GERD patients.Esophageal peristalic contraction may be associated with esophageal injury and acid reflux.

Objective To investigate the dynamic changes of adenosine receptors, A1 (A1R) and A2a (A2aR) in the brain from the acute to chronic phase after kindling and to explore the correlation between seizure and expression level of A1R and A2aR. MethodsRats were randomly selected into the testing model, reference and normal control groups.Testing rats were kindled by lithium choride-pilocarpine, reference rats were treated with saline, and no treatment was given in normal control group. The dynamic expression of A1R and A2aR were detected by RT-PCR, immunofluorescence staining and Western blot at time-points of 24 hours, 1 month and 6 months post-kindling. Results In the acute phase of 24 hours after kindling, the A1R expression level (mRNA level was (1. 1483 ±0. 1182); Western blot result was ( 0. 7872± 0. 0621 ) ; immunofluorescence staining count was ( 76. 17 ± 4. 62 )/HP) was increased and A2aR (mRNA level was (0. 8338±0. 0572) ; Western blot result was (0. 2098 ±0. 0257) ; immunofluorescence staining count was (43. 83 ± 5. 12 )/HP) was decreased.The results showed statistically difference compared with the reference and normal groups (P< 0. 05 ). In the later chronic phase of 1 month and 6 months after kindling, the expression level of A1R was decreased and A2aR was increased. These data revealed statistically significant difference (P <0. 01 ). Furthermore, the comparison of the results in 1 month and 6 months after kindling found that the expression of AIR was lower in 6 months (mRNA level was (0. 5682 ±0. 0443) ; Western blot result was (0. 7749 ±0. 0262) ; immunofluorescence staining count was (38. 50 ±4. 81 )/HP) than in 1 month and that of A2aR was higher in 6 months (mRNA level was (1. 2169±0. 0332) ; Western blot result was (0. 7080 ±0. 0371 ); immunofluorescence staining count was (114. 50 ± 4. 04)/HP). The differences were statistical significant (t = - 19. 02--13.28, P < 0. 05). ConclusionsThe expressions of A1R and A2AR during and after kindling presents a bidirectional change. In the acute phas the expression of AR is regulated to suppress seizures. While in the chronic phase, the repeated seizures result in the change of A1R and A2aR expression in the opposite direction. This mechanism plays an important role in refractory seizures.

Objective To evaluate the clinical applications and surgical methods of combined laparoscopic common bile duct (CBD) exploration with choledochoscopy. Methods From 2006 to 2009,clinical data of 42 patients with choledocholithiasis undergoing laparoscopic common bile duct exploration were retrospectively analyzed. We applied a step-by-step electric coagulating incision technique on the CBD,the step-by-step suturing technique, and the step-by-step clamping technique with alligator forceps, and soft tube irrigating technique with suctioning by selecting the proper exploration route, improving the common bile duct incision technique and calculus removing techniques. Results Procedures were successful in all the cases. There was no conversions to open surgery, no postoperative bleeding and no operative mortality. The mean operating time was 120 minutes (ranging, 90 to 150 minutes) with minimal intraoperative blood loss ( ranging, 20 to 40 ml). Ductal stone clearance was successful in 41 out of 42 patients ( 93% ). The largest number of the common bile duct stones was 16. With the diameter of stones larger than 15 mm in 18 cases in which the biggest was 30 mm. Bile leak developed in 1 patient, retained stones found in 3 patients,including intrahepatic cholelithiasis in one case. As a result, 38 out of 42 patients underwent common bile duct exploration. 35 patients were placed on T-tubes. Four patients underwent cystic duct exploration in which 3 had primary suture of the cystic duct and 1 had drainage. There was no infection and stenosis of biliary tract in the 42 followed-up cases. Conclusions Laparoscopic common bile duct exploration with stone extraction can be performed with high efficiency, minimal morbidity and without mortality. Improving the way of operation and selecting suitable exploration can result in better clinical outcomes.

Following the wishes of volunteer patients,316 cases of type 2 diabetics of our community center in 2008 carried out a three-year intervention from 2008 to 2011 on the basis of rational drug therapy plus the interventions of health education,regular review and lifestyle strengthening.And regular monitoring and recording were performed on the parameters of body mass index (BMI),blood pressure,blood lipids,fasting glucose,2 h postprandial blood glucose,glycosylated hemoglobin (HbA1c) and liver & kidney function.After intervention,some indicators changed:BMI (25.2 ±3.5) vs.(25.0 ±3.3) kg/m2,systolic blood pressure (129.1 ± 11.8) vs.(126.2 ±7.9) mm Hg(1 mm Hg=0.133 kPa),fasting glucose (7.80 ±2.81) vs.(7.25 ± 1.96) mmol/L,2 h postprandial blood glucose (11.04 ±4.60) vs.(9.83 ±3.60) mmol/L,HbA1c (7.39 ± 1.61) vs.(7.17 ± 1.65)％,total cholesterol (5.08 ±1.21) vs.(4.74 ± 1.35) mmol/L,low density lipoprotein cholesterol(LDL) (3.09 ± 0.87) vs.(2.85 ±0.83) mmol/L,high density lipoprotein cholesterol (HDL) (1.27 ± 0.33) vs.(1.41 ± 0.32) mmol/L,serum creatinine 65 vs.72 μmol/L,uric acid 300 vs.317 μmol/L.And the differences were statistically significant (P ＜ 0.05).After intervention,blood pressure compliance rate increased from 72.5％ to 88.0％,LDL-C compliance rate improved from 27.2％ to 38.6％,HDL-C compliance rate of 54.9％ increased to 66.9％.And the differences were statistically significant (P ＜ 0.05).The pre-intervention combined compliance rate of 11.4％ (n =36) rose to 17.7％ (n =56).And there was significant difference (P =0.024).

Objective To examine the effects of exogenously administered intermedin (IMD,adrenomedullin-2) on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n =12),SHR group (n =12),IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour,n =12),and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour,n =12).Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax),left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2),aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor (CRLR);suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP).Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.

Objective To study the effect of metastasis-associated in colon cancer 1 ( MACC1 ) inhibition by small interference RNA( siRNA) on the formation of tumor cells that promote blood vessels, and to explore its possible molecular mechanism.Methods Synthesized MACC1 specific siRNA was transfected into human lung cancer cell lines XWLC-05. Then, the inhibitory effect of siRNA on the protein level of MET, MEK/p-MEK, ERK/p-ERK, and AKT/p-AKT was detected using Western blotting while the change in VEGF, bFGF and IL-8 protein level was detected using ELISA method. Results Western blotting results indicated that the expression level of MET, p-MEK and p-ERK was significantly decreased in the XWLC-05 cells transfected by MACC1 specific siRNA compared with control and nonsense siRNA groups, but the expression of total protein MEK and ERK did not change.Furthermore, the level of AKT and phosphorylated protein was not affected.ELISA results suggested that the secretion level of VEGF, bFGF and IL-8 was significantly suppressed at 48 h or 72 h compared with control and nonsense siRNA groups.Conclusion MACC1 may reduce the secretion levels of VEGF, bFGF and IL-8 via HGF/c-Met and MEK/ERK signal transduction pathways, and regulate angiogenesis of lung cancer.

AIM:To observe the effect of B-HT933, a selective α2-adrenoceptor agonist, on lipopolysaccha-ride ( LPS )-induced TNF-αproduction in neonatal rat cardiomyocytes and to explore the underlying mechanisms . METHODS:The neonatal rat cardiomyocytes were cultured .The localization of α2A-adrenoceptor in the cardiomyocytes was examined by immunofluorescence staining .The cardiomyocytes were exposed to LPS or/and B-HT933 for different time.The level of TNF-αin the supernatants and the mRNA expression of TNF-αwere detected by ELISA and real-time PCR, respectively.In addition, LPS-associated signal molecules in the cardiomyocytes were also examined by Western blotting.RESULTS: Immunofluorescence staining showed that α2A-adrenoceptors were localized in the cardiomyocytes . LPS stimulated TNF-αproduction in the cardiomyocytes in a dose and time-dependent manner .B-HT933 pretreatment sig-nificantly inhibited the expression of TNF-αat mRNA and protein levels in LPS-treated cardiomyocytes .Furthermore, LPS exposure induced IκBαand p38 phosphorylation in cardiomyocytes and only IκBαphosphorylation was prevented by B-HT933 treatment.CONCLUSION:α2A-adrenoceptors are present in neonatal rat cardiomyocytes and its agonist B -HT933 inhibits LPS-induced TNF-αproduction in cardiomyocytes via suppressing IκBαphosphorylation .

OBJECTIVETo observe the effect of composite factors, like long-term high-salt & fat diet and alcohol abuse on blood viscosity and blood pressure in rats, and compare with a model induced by high molecular dextran, in order to build a chronic hyperviscosity aminal model which is similar to human hyperviscosity in clinic and lay a foundation for efficacy evaluation on traditional Chinese medicines.

METHODMale SD rats were randomly divided into the normal group, the high molecular dextran (HMD) group and the high salt & fat and alcohol (HSFA) group. The HMD group was given normal diet and water for 23 day and then 10% HMD through tail vein for 5 days. The HSFA group was fed with high salt and high fat diets every day and alcohol for 20 h x d(-1) for 13 weeks. After the modeling, whole blood viscosity and plasma viscosity were measured in the 5th, 8th and 11th week. Blood pressure was measured in the 5d, 7h, and 10th week. Red cell count (RBC) and hematocrit (HCT) were measured in the 11th week. PAgT, Fb, ET-1, NO, PGI, TXA2 contents of the normal group and the HSFA group were measured in the 13th week, and IECa21 content was measured with flow cytometry. Result: After the modeling, the HMD group was in good conditions with glossy hairs and active behaviors. The HSFA group was depressed with withered hairs and less activities. During the 5th-11th weeks, the HMD group and the HSFA group showed higher values in high and low shear whole blood viscosity (WBV) than the normal control group. The plasma viscosity (PV) of HMD rats was significantly increased only in the 5th week, and that of HSFA rats significantly increased in the 8"' and 11th week, particularly in the 11'h week. In the 111h week, the HSFA group showed significant increases in RBC and HCT. After the modeling, the blood pressure of HMD rats showed no significant changes, but the blood pressure of HSFA rats significantly increased during 7' and 101h weeks, particularly in the 10"' week. In the 13th week, PAgT, IECa2+, Fb, ET-1 of HSFA rats significantly increased, but with decreases in NO and PGI2.

CONCLUSIONLong-term high salt & fat and alcohol diets can cause abnormal blood viscosity in rats. WBV significantly increased since the 5th week in rats, and PV increased since the 8th week. The mechanism for increasing BV may be: (1) increases in RBC, HCT, and IECa2+, (2) PAgT increase, (3) Fb content increase, or (4) TXA2/PGI2, ET-1/NO imbalance. Although the modeling time with the method is longer than that with the HMD method, the model is more stable and moderate, and could lead to abnormal increases in WBV and PV; Whereas the HMD method only induced transient increase in plasma viscosity and abnormal increase in SBP. The model is more similar to traditional Chinese medicine syndromes and pathogenesis, with higher value for studies on efficacy of traditional Chinese medicines.

Alcoholism ; blood ; metabolism ; Animals ; Blood Pressure ; Blood Viscosity ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Ethanol ; adverse effects ; metabolism ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary ; adverse effects ; metabolism

ObjectiveTo evaluate the potential value of acoustic radiation force impulse (ARFI)elastography in the characterization of solid liver tumors.MethodsForty-three patients with 56 liver tumors were evaluated with ARFI,which included 21 patients with hepatocellular carcinoma (HCC),8 patients with metastase,5 patients with cholangiocarcinoma(CCC),and 9 patients with hemangioma.The shear wave velocity of the tumor and background liver parenchyma were calculated,and results were compared with 30 healthy subjects.Statistical analysis was performed on the shear wave velocity for differentiation of normal liver,background liver parenchyma,and tumors.ResultsHCC and CCC had greater stiffness than metastase (P ＜0.05),there were no statistical differences between HCC and CCC (P = 0.179).Malignant liver tumors had significantly greater stiffness than hemangioma and normal liver (P = 0.000).34.5% (9/26) HCC and 33.3% (4/12) hemangioma appeared softer than the background liver.With a cut-off value of 1.5 m/s for the shear wave velocity,the sensitivity,specificity,positive predictive value and negative predictive value for malignancies were 79.5%,83.3%,94.5% and 52.6%,respectively.ConclusionsARFI elastography quantification is a promising noninvasive technique for assessing solid liver tumors.Use of ARFI elastography quantification may lead to new quantitative tissue characterization parameters for differentiating hemangioma and malignant liver tumors.