OBJECTIVE:To investigate the effectiveness and economics of 10 mg/d rosuvastatin and 20 mg/d atorvastatin in the treatment of hyperlipidemia (HLP). METHODS:The information of 180 HLP patients selected from Tianmen Municipal First People's Hospital during Mar. 2015-Feb. 2016 were divided into group A and B according to medication regimen,with 90 cases in each group. Group A was given Atorvastatin calcium tablet 20 mg,qd;group B was given Rosuvastatin calcium tablet 10 mg,qd. Treatment course of 2 groups lasted for 8 weeks. Blood lipid indexes before and after treatment,lipid-lowering efficacy,the rate of qualified blood lipid and the occurrence of ADR after treatment were compared between 2 groups. Cost-effectiveness analysis was adopted for economic evaluation. RESULTS:Before treatment,there was no statistical significance in the levels of blood lipid in-dexes between 2 groups (P>0.05). After treatment,TC and LDL-C levels of 2 groups were significantly lower than before treat-ment,and those of group B were significantly lower than those of group A,with statistical significance(P<0.05). Total response rate of lipid-lowering in group B(97.78％)was significantly higher than group A(86.67％),and the rate of qualified blood lipid (66.67％)was also significantly higher than group A(51.11％),with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). The costs of group A and B were 488.32,436.24 yuan,and cost-effectiveness ratios were 5.63,4.46;incremental cost-effectiveness ratio was -4.69. The plan of group B had cost-effective-ness advantage. The results of cost-effectiveness analysis were supported by sensitivity analysis. CONCLUSIONS:In the view of short-term efficacy,10 mg/d rosuvastatin plan is better than 20 mg/d atorvastatin plan in lowering lipid and has cost-effectiveness advantage,and both have similar safety.

ObjectiveTo investigate effects of anisodamine on myocardial caspase-1 and interleukin-18 expression following overtraining-induced acute myocardial injury in rats.Methods Forty-eight male Wistar rats weighing 200-220 g were randomly divided into 3 groups:group control (group C,n =8) ; group exhausting swim (group ES,n =24) and group anisodamine (group AD,n =16).The animal model of overtraining-induced acute myocardial injury was developed by exhausting swim The animals were forced to swim until they were exhausted.The animals sank to the bottom and no righting reflex or escape response was elicited when they were taken out of water in groups ES and AD.In group AD anisodamine 10 mg/kg was given intraperitoneally 20 min before overtraining.Blood samples were taken from inferior vena cava immediately (T1) and at 6 and 24 h after overtraining (T2,T3 ) in group ES and at T2,T3 in group AD for determination of serum cardiac troponin 1 (cTnI) concentration (by ELISA).The animals were sacrificed after blood sampling and myocardial specimens were obtained for microscopic examination and determination of caspase-1 and interleukin-18 expression (by immuno-histochemistry).ResultsOvertraining significantly increased serum cTnI concentration and up-regulated myocardial caspase-1 and interleukin-18 expression in group ES as compared with group C.Anisodamine significantly attenuated overtraining-induced increase in serum cTnI concentration and myocardial caspase-1 and interleukin-18 expression in group AD as compared with group ES.ConclusionAnisodamine can reduce overtraining-induced acute myocardial injury by down-regulating caspase-1 and interleukin-18 expression.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1^Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.