Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.

Objective To evaluate the clinical value of tissue Doppler imaging(TDI)in assessing left ventricular(LV)function after mitral valve replacement(MVR).Methods Forty-five patients having their implantations for more than three months were examined by echocardiography and divided into atrial fibrillation group(AF group,n=21)and sinus rhythm group(SR group,n=24).Thirty normal volunteers served as control group.Left atrium and ventricle indexs of cardiac function and mitral inflow velocity(E)were measured by two dimensional and Doppler echocardiography,and TDI-derived systolic mitral annular velocity(Sm),diastolic mitral annular velocity(Em)and isovolumic relaxation time(IVRT)were measured at the septal and lateral corners of mitral annulus from the apical four-chamber view.Then E/Em ratio was calculated.Results ①Compared with control group,Sm and Em in MVR group were significantly lower and IVRT was higher(P＜0.001),however there were no significant differences between AF group and SR group.② The E/Em ratio in MVR group was significantly higher than that in control group(P＜0.001)and positively correlated with IVRT.The best cutoff value for E/Em ratio was increased of 15 which yielded the sensitivity and specificity in predicting LV diastolic dysfunction were 91.11% and 90.32%,respectively.The area under the ROC curve was 0.9548±0.0402.Conclusions TDI-defived indexes(Sm,Em)can assess LV function accurately and the E/Em ratio,an estimate of myocardial relaxation and LV filling pressures,can be used to evaluate left ventricular diastolic function after MVR.

Objective To assess left ventricular systolic strain in patients with mitral valve replacement (MVR) by speckle tracking echocardiography. Methods Two-dimensional images were acquired from the apical four-chamber view, two-chamber view and long-axis of the left ventricular view in 30 MVR patients (MVR group) and 30 healthy subjects matched by age and gender(control group), and then were analysed off line to evaluate left ventricular systolic strain. The maximum systolic longitudinal strain(LS) of myocardial segments and global longitudinal strain(GLS) were measured in apical views. Left ventricular ejection fraction(LVEF) was calculated using Simpson's method. The correlation between GLS and LVEF was analyzed using Pearson's method. Results Compared with the control group, LS of corresponding segment and GLS in MVR group decreased significantly (P < 0.01), but there were no statistical differences within MVR group(P>0.05). There was a good linear positive correlation between GLS and LVEF in patients (r = 0.710, P <0.01). Conclusions Speckle tracking eehoeardiography is available for measuring left ventricular systolic strain and estimating global systolic function in patients with MVR. Bull's-eye strain map, created by speckle tracking imaging, can achieve an accurate real-time segmental wall motion analysis.

Objective To evaluate the clinical value of color M-mode Doppler echocardiography (CMM) in assessing left ventricular(LV) diastolic function after mitral valve replacement(MVR). Methods Fifty-two patients who had received the implantation for more than three months were examined by echoeardiography (MVR group). Thirty age and sex-adjusted normal volunteers served as control group. Dimensions of left atrium and ventricle,ejection fraction(EF) and mitral inflow velocity(E) were measured by two-dimensional and Doppler eehocardiography. Color M-mode Doppler flow propagation velocity(Vp) and TDl-derived diastolic mitral annular velocity(Em) were measured from the apical four-chamber and two-chamber views. Then two new indexes based on the ratio of E to Vp(E/Vp) and E to Era' (E/Em') were while E/Vp and E/Era' increased, there were significant differences(P <0.01). The correlation coefficient and atrial fibrillation(P <20.01) ,however E/Vp was lower affected hy EF or atrial fibrillation(P >0.05). dysfunction were 2.00. Conclusions CMM is an effective technique to assess LV diastolic function after MVR. E/Vp has good consistency with E/Era and may be a potential useful parameter for assessing LV diastolic function.

OBJECTIVE To investigate the distribution and resistance of clinical isolates to antimicrobial agents commonly used.Antimicrobial agents should be used rationally based on the results of susceptibility testing.METHODS The clinical isolates were identified with W/A-40 or VITEK-32.The results were analyzed by WHONET 5.3 software according to CLSI 2005.RESULTS A total of 2892 clinical isolates were collected in 2007.Gram-negative bacilli accounted for 68.2% and Gram-positive cocci accounted for 31.8%.The top eight pathogens were Pseudomonas aeruginosa,Escherichia coli,Klebsiella spp,Acinetobacter spp,coagulase-negative Staphylococcus,Enterobacter spp,Serratia spp and S.aureus.About 76.4% of S.aureus isolates were MRSA,81.6% of coagulase-negative Staphylococcus isolates were meticillin-resistant.Under 20.0% of Enterobacteriaceae strains were resistant to cefoperazone/sulbactam,imipenem and piperacillin/tazobactam.About 16.3% and 32.5% of P.aeruginosa isolates were resistant to cefoperazone/sulbactam and imipenem.CONCLUSIONS Gram-negative bacilli were dominant isolates in our hospital during 2007.P.aeruginosa is the most frequent pathogenwith severe antibiotic resistance.Enterobacteriaceae are susceptible to cefoperazone/sulbactam and imipenem.

Objective To compare broth microdilution and agar dilution methods for in vitro testing of activities of fluconazole,ketoconazole and itraconazole against clinical Malassezia isolates.Methods Broth microdilution and agar dilution methods were used to determine the minimal inhibitory concentration(MIC)of fluconazole,ketoconazole and itraconazole for 27 clinical strains(5 species)of Malassezia.Results The minimal inhibitory concentration(MIC)ranges of fluconazole,ketoconazole and itraconazole were 0.25-≥64 mg/L,≤0.03-0.5 mg/L and ≤0.03-0.125 mg/L respectively as shown by broth microdilution method,2-≥64 mg/L,≤0.03-0.5 mg/L and ≤0.03-0.25 mg/L respectively as revealed by agar dilution method.Both methods demonstrated that itraconazole possessed the strongest activity against Malassezia species,followed by ketoconazole and fluconazole.The agreement rate in MICs between the two methods was 78.8％,85.2％ and 88.9％,respectively for fluconazole,ketoconazole and itraconazole,with the intraclass correlation coefficients (ICCs)being 0.88,0.80 and 0.76 respectively.Conclusions Fluconazole,ketoconazole and itraconazole are highly active against Malassezia species in vitro,and itraconazole is the most active.Broth microdilution and agar dilution method coincide well in,and are applicable for,the antifungal susceptibility testing of Malassezia species in vitro.

Objective To determine the extracellular enzymatic activity of common pathogens for onychomycosis, in the hope of finding virulence factors associated with the pathogenesis of onychomycosis. Methods Strains tested in this study included standard strains of common dermatophyte and non-dermatophyte fungi as well as clinical isolates of Trichophyton rubrum from patients with onychomycosis. All the tested strains were cultured in medium containing nail fragments at 25 ℃ for 10 to 21 days followed by the determination of the nail fragment-containing medium, a significant increase was observed in the activities of esterase, esterase lipase, N-acetyl-β-glucosaminidase and α-mannosidase in dermatophytes compared with non-dermatophytes (all P ＜ 0.05 ), as well as in the activity of N-acetyl-β-glucosaminidase in Trichophyton rubrum compared with the other tested species of fungi (all P ＜ 0.05). No significant difference was noted in the activity of extracellular enzymes, except for that of naphthol-AS-BI-phosphohydrolase, between the isolates of Trichophyton rubrum from patients with different ranges of scoring clinical index for onychomycosis (SCIO). Conclusions In specific conditions, the extracellular enzymatic activity of fungi isolated from patients with onychomycosis is associated with fungal species, and may have a certain influence on the manifestations of anychomycosis.

Aromatase is a key enzyme responsible for in vivo estrogen biosynthesis. Inhibition of the activity of the aromatase has become an alterative way for treatment of breast cancer. In this review, the structure and catalytic mechanism of the aromatase is briefly introduced followed by thorough review of the progress in the study of the steroidal and non-steroidal aromatase inhibitors. This review is focused on the natural compounds that exhibit the aromatase inhibition, which include flavonoids, xanthones, coumarins, and sesquiterpenes. The structure-activity relationship of these compounds is also discussed.

ObjectiveTo investigate the predisposing factors and pathogenic fungal species of Malassezia folliculitis in different geographical areas and body sites.MethodsTotally,241 patients diagnosed with Malassezia folliculitis were asked to complete a questionnaire.The content of hair follicles was obtained and subjected to fungal smear and culture examination.Fungal species were identified according to morphological,physiological and biochemical features.Results Of the 241 patients with Malassezia folliculitis,204 (84.65％) were positive for smear examination.A total of 259 specimens were collected from these patients,and fungal culture grew 213(82.24％) strains,of which,209 belonged to Malassezia species,4(1.54％) to Candida species.Among the 209 Malassezia strains,186 were activated and subjected to species identification which resulted in 6 species,including M.furfur (111 strains,59.68％ ),M.sloofiae (43 strains,23.12％ ),M.sympodialis (17 strains,9.14％),M.globosa (9 strains,4.84％),M.pachydermatis (4 strains,2.15％),and M.obtuse(2 strains,1.08％ ).Of the pathogenic fungi of Malassezia folliculitis,M.furfur predominated in the chest,back,abdomen,face and neck,M.sloofiae in the upper limbs,shoulders and vertex,M.globosa in the lower limbs.There were obvious differences in the distribution of pathogenic fungal species at different body sites in a same host,and M.furfur with M.sloofiae or M.sympodialis appeared to be the most common pathogens.ConclusionsIn this study,6 Malassezia species are identified in patients with Malassezia folliculitis in Nantong and Nanjing area,M.furfur and M.sloofiae appear to be the dominant pathogens.