Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities. But the clinical use is limited by its low bioavailability. The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use. The transport characteristics and mechanisms of limonin in rat were studied by in situ intestine perfusion and in vitro Caco-2 cells method. The intestinal absorption of limonin was probably via a facilitated diffusion pathway which was poor and without segment-selection. Verapamil and ketoconazole improved the absorption remarkably according to the result of in vitro Caco-2 cells study; however, probenecid had no significant effect on the absorption. The P-gp efflux and CYP3A4 metabolism were involved in the poor intestinal absorption and low bioavailability of limonin. The exploration of the intestinal absorption mechanism is crucial to the design of dosage form and clinical use of limonin.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Biological Availability ; Biological Transport ; drug effects ; Caco-2 Cells ; Cytochrome P-450 CYP3A ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Intestinal Absorption ; drug effects ; Ketoconazole ; pharmacology ; Limonins ; administration & dosage ; pharmacokinetics ; Male ; Perfusion ; Probenecid ; pharmacology ; Rats ; Verapamil ; pharmacology

Objective To investigate the relationship between putative rs5744168 of Toll-like receptors 5 (TLR5)and ANCA associated small vasculitis (AAV) in Guangxi Han nationality. Methods Polymorphism was analyzed by polymerase chain restricted fragments length polymorphism in 120 cases with AAV and 212 controls. Results (1)There were two genotypes of CC and CT in AAV group and control group. The frequencies distribution of CC and CT in 120 AAV patients were 82.50% and 17.50% respectively and the frequencies of allele C and T 91.25% and 8.75%,respectively. In controls,the genotypefrequencies of CC and CT were 88.68% and 11.3%, and frequencies of allele C and T 94.34% and 5.66%, respectively. No significant difference was found in either genotype distribution or allele frequencies between the patients and the controls ( P > 0 . 05 ) . ( 2 ) Significant reductions in the incidence of BUN, uric acid, quantitative test of 24 h urinary protein and erythrocyte sedimentation rate(ESR) were found in CC genotype (P < 0.05). (3) Binary regression model with a logit link function found total cholesterol was related with AAV. Conclusion The susceptibility of AAV in Guangxi Han population has nothing to do with the polymorphism of rs5744168.In AAV patients, polymorphism of rs5744168 may be associated with ESR, BUN, uric acid and quantitative test of 24 h urinary protein levels.

Objective To investigate the correlation between Toll-like receptor2 (TLR2) gene promoter region -597T/C polymorphism and primary ANCA associated small vasculitis (AAV) in Guangxi Han people. Methods A case contrastive control study was adopted in the study. Patients with AAV (patients group, n=110) and healthy people (control group, n = 200) were recruited. Associated serum indexes were detected and polymorphisms of TLR2 gene promoter 597T/C were analyzed by polymerase chain restricted fragment length polymorphisms (PCR-RFLP). Results (1)Three TLR2-597T/C genotypes were discovered in 110 AAV patients, namely, TT, TC and CC, with the frequency of 54.55%,40.00% and 5.45% respectively. And the frequencies of allele T and C were 74.55% and 25.45%. In control group, the genotype frequencies of TT, TC and CC were 56.00%,40.50% and 3.50%, with 76.25% of allele T and 23.75% of allele C. No significant differences were found in neither genotype distribution nor allele frequencies between the patients group and control group ( P > 0 . 05 ) . ( 2 ) Significant differences were found in the incidence of proteinuria rate and the hemoglobin (P< 0.05)in AAV patients. (3)There was no significant difference between AI and CI in TT, TC and CC genotype in AAV patients. Conclusions Polymorphism of TLR2-597T/C may be correlated with the incidence of proteinuria and the level of hemoglobin, while no obvious correlation with the genetic susceptibility of ANCA in vasculitis patients of Guangxi Han people.

Objective To express,purify and identify recombinant hepatitis E virus(HEV) pb166-GST fusion protein using GST gene fusion system and investigate its potential role in researching Hepatitis E diagnostic antigen field.Methods The recombinant E.coli BL21 performed by our own laboratory was used to induce the HEV pb166-GST expression with IPTG.The products were purified by BD Biosience GST purifying system.The specific expression was identified by SDS-PAGE and Western blot.The experiment conditions and results were described and analysed.Results The resolved HEV pb166-GST fusion protein on SDS-PAGE showed a major band at position of 43 kD.The expressed proteins had a single expected band after purify and the protein was recognized by anti-GST antibody on PVDF membrane.Conclusion The recombinant HEV pb166-GST fusion protein is expressed in recombinant E.coli BL21 efficiently in this way,and might be used as a candidate for diagnostic antigen of HEV.

Objective To assess the clinical value of endoscopic uhrasonography(EUS)combined with the mini-probe endoscopic uhrasonography(MPUS)in determing tumor invasion depth and lymph node metastases of early superficial esophageal cancer.Methods One hundred and twenty-four superficial esophageal cancer lesions of 121 patients were staged by EUS combined with MPUS,and the results were finally compared with pathological findings of surgical specimens or samples obtained by mucosal resection.Results The diagnostic accuracy of EUS in T staging of superficial esophageal cancer was 82.3%(102/124).The total ratio of lymph node metastases was 5.0%(6/121),with no node metastases in carcinoma in situ,1.3%(1/28)in mucosal carcinoma,11.6%(5/43)in submucosal carcinoma.Conclusion EUS combined with MPUS is accurate in staging of the superficial carcinoma,which can help the choice of therapeutic strategies.

BACKGROUND:The treatment of acute myocardial infarction (AMI) is thought to restore antegrade blood flow in the infarct-related artery (IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-reflow in patients with AMI after primary percutaneous coronary intervention (PCI). METHODS:A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were:(i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or (ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were:(i) coronary artery spasm; (ii) diameter stenosis of the culprit lesion was ≤50％ and coronary blood flow was normal; (iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction (TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography findings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-reflow. RESULTS:Fifty-four (17.3％) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure (SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump (IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow (P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95％ confidence interval (CI) 1.460–1.490,P=0.007], long time from onset to reperfusion >6 hours (OR=1.270, 95％CI 1.160–1.400,P=0.001), low SBP on admission <100 mmHg (OR=1.910, 95％CI 1.018–3.896,P=0.004), IABP use before PCI (OR= 1.949, 95％CI 1.168–3.253, P=0.011), low (≤1) TIMI flow grade before primary PCI (OR=1.100, 95％CI 1.080–1.250,P<0.001), high thrombus burden (OR=1.600, 95％CI 1.470–2.760,P=0.030), and long target lesion (OR=1.948, 95％CI 1.908–1.990,P=0.019) on angiography were independent predictors of no-reflow. CONCLUSION:The occurrence of no-reflow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.

Objective:To analysis the construction of the world's top PhaseⅠclinical trial registration agencies, compare their size, composition, operation and funding, to provide further reference for the construction of clinical trial agency in China.Methods:Search for PhaseⅠclinical trial research agencies by region on clinicaltrials.gov. Collecting information about the agency’s management, staffing, implementation in Asia, America and Europe. Descriptive analysis was carried out to explore the type, proportion and operation among different regions, the organizational structure, operational management and effectiveness of each agency from different regions were compared.Results:The United States, Europe and East Asia are dense areas of PhaseⅠclinical research around the world. The types of agencies in the United States, Britain, France, Germany, South Korea, Japan, and Israel are mainly enterprises. Among other types of agencies, the organizational models are diversified. The agencies have different spatial distances from medical institutions, but possess relatively consistent scale and institutional operation. All the agencies have a stable source of funding.Conclusions:In order to strengthen the construction of clinical trial agencies in China, we should speed up the establishment of a close connection mechanism to promote deep cooperation in clinical trials. Control the construction scale and maintain stable input of the agency. Meanwhile, establish and strengthen international exchanges and cooperation.

Objective:To study the international situation of technology innovation and transfer, to improve the performance in the health field of China.Methods:Collect data and status quo of innovation and transformation of scientific and technological achievements in 10 World-class research universities and hospitals through literature review, and conduct summary analysis.Results:According to the study, the health field is the main arena of technology innovation and transfer in which the status of the main body of innovation of hospitals cannot be ignored, and the transformation ability of some hospitals is higher than universities.Technology innovation and transfer in the health field is characterized by multiple disciplines, long-term and high cost, and it is necessary to build a full ecological chain from research and development (R&D) to production and commercialization.Conclusions:The dominant position of the health field and hospitals in technology innovation and transfer needs to be emphasized.Interdisciplinary collaboration and innovative economy building should be strengthened.

Objective To investigate the relationship between serum thyrotrophin(TSH)and dyslipidemia in subclinical hypothyroid and euthyroid subjects. Methods An epidemiological study on diabetes and thyroid diseases was performed in Dadong community, Shenyang city, in 2007. 110 subjects with subclinical hypothyroidism(SCH)and 1 240 euthyroid subjects were enrolled in the study. Neither history of thyroid diseases nor administration of thyroid-related and lipid-regulating medicines were reported in these subjects. The levels of serum thyroid hormones, lipids, fasting plasma glucose(FPG), and insulin were determined. Results (1)Patients with SCH had significantly lower HDL-C levels than those who were euthyroid.(2)According to the guideline of treatment of adult dyslipidemia in China, the lipid profiles were each categorized. Mean TSH levels were higher in subjects in the dyslipidemia subclass than subjects in the normal subclass. The differences were significant in high LDL-C subclass in overweight individuals. In euthyroid overweight women, mean TSH levels were significantly higher in high LDL-C subclass. In the euthyroid population, TSH was positively associated with total cholesterol in overweight population. The association was not modified by the homestasis model assessment for insulin resistance(HOMA-IR)values.(3)TSH was associated positively with serum triglycerides and negatively with serum HDL-C in women. TSH was positively associated with total cholesterol in overweight population and positively associated with total cholesterol and LDL-C in overweight women after adjustment for age, sex, and body mass index. Conclusion Raised serum TSH seems to be a risk factor of dyslipidemia in subclinical hypothyroid and euthyroid subjects, which is independent of insulin sensitivity.

OBJECTIVETo investigate the clinicopathologic features of primary nodal marginal zone B-cell lymphoma (NMZL).

METHODSHematoxylin-Eosin staining and immunohistochemistry were used to evaluate the histological and immunophenotypic characteristics of lymph node (LN) tissue in 22 NMZL cases. Additionally, interphase fluorescence in-situ hybridization (FISH) was carried out to detect the presence of t(11;18) (q21;q21)/API2-MALT1 and/or t(14;18)(q32;q21)/IGH-MALT1 in 9 cases.

RESULTSThe median age of the 22 patients was 62 (16 - 77) ys. The male-to-female ratio was 1.2:1. All patients exhibited asymptomatic lymphadenopathy with the cervical region as the most often site to be involved (n = 11), followed by axillary (n = 9), inguinal (n = 7), submandibular (n = 6), mediastinal (n = 4), supraclavicular (n = 2) and retroperitoneal lymph nodes (n = 1). The Ann Arbor stages were I/II in 13 (59%) cases and III/IV in 9 (41%). Immunohistochemical study showed a consistently strong expression of CD20 and an absence in the expression of CD3ε, CD10, CD21, CD23, CyclinD1 and BCL6 by the tumor cells in all the cases. Frequency of expression of CD5 and BCL2 were 39% (7/18) and 30% (3/14) respectively. Among the 9 cases performed with FISH, 2 cases harbored t(14;18)and another 1 case positive for t(11;18) and t(14;18). Complete follow-up data were available for 13 cases. The follow-up time was 6 to 44 months. 3 of them died. 3-year cumulative survival rate was 67%.

CONCLUSIONSNMZL patients are often elderly, which mainly present with multiple lymphadenopathy, rare involvement of extranodal organ and early stage. The diagnosis must be based on a combination of clinicopathologic features, especially those patients detected t(11;18) and/or t(14;18).

Adolescent ; Adult ; Aged ; Biopsy ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymph Nodes ; pathology ; Lymphoma, B-Cell, Marginal Zone ; diagnosis ; pathology ; Male ; Middle Aged ; Prognosis ; Survival Rate ; Young Adult