Baicalin protects against 17α-ethinylestradiol-induced cholestasis via Sirt1/HNF-1α/FXR pathway / 中国药理学与毒理学杂志

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.

Mechanism of Calculus Bovis Sativus in inhibiting hepatocyte lipid deposition based on serum pharmacology / 中国中药杂志

The aim of this paper was to investigate the molecular mechanism of Calculus Bovis Sativus( CBS) in alleviating lipid accumulation in vitro by serum pharmacology. The CBS-containing serum of mice was obtained by serum pharmacology method to evaluate its effect on the proliferation of LO2 hepatocytes. The lipid reducing effects of CBS-containing serum through Nrf2 was evaluated by fructose-induced LO2 hepatocyte steatosis model,nuclear factor erythroid 2 related factor 2( Nrf2) agonist oltipraz combined intervention,cell oil red O staining and intracellular triglyceride( TG) content. The effects of CBS-containing serum on lipid peroxidation and hepatocytes apoptosis were evaluated by reactive oxygen species( ROS) and apoptosis assay,respectively. Real-time quantitative polymerase chain reaction( PCR) was used to detect the relative expression of lipid synthesis-related genes and apoptosis-related genes.RESULTS:: showed that CBS drug-containing serum had no significant effect on LO2 hepatocyte proliferation. As compared with the model group,CBS-containing serum could effectively reduce the formation of lipid droplets in fructose-induced LO2 hepatocytes,significantly reduce intracellular TG and ROS levels,and significantly reduce hepatocyte apoptosis rate( P < 0. 05). As compared with the model group,carbohydrate responsive element binding protein( ChREBP),sterol regulatory element binding protein-1 c( SREBP-1 c),fatty acid synthase( FAS),acetyl-CoA carboxylase 1( ACC1),stearoyl-CoA desaturase 1( SCD1),Bax and caspase-3 mRNA levels were significantly reduced in CBS drug-containing serum treatment group( P<0. 05). All of the above effects could be reversed by oltipraz.In conclusion,CBS-containing serum can significantly inhibit the fructose-induced LO2 liver fat deposition,and the mechanism may be related to reducing intracellular ROS level through the Nrf2 pathway and improving intracellular peroxidation state to reduce apoptosis.

Association of hypoalbuminemia with acute kidney injury in children after cardiac surgery / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study whether hypoalbuminemia after pediatric cardiopulmonary bypass (CPB) for cardiac surgery is a risk factor for postoperative acute kidney injury (AKI).</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data of 1 110 children who underwent CPB surgery between 2012 and 2016. According to the minimum serum albumin within 48 hours postoperatively, these patients were divided into hypoalbuminemia group (≤35 g/L) and normal albumin group (>35 g/L). The two groups were compared in terms of perioperative data and the incidence of AKI. Furthermore, the incidence of AKI was compared again after propensity score matching for the unbalanced factors during the perioperative period. The perioperative risk factors for postoperative AKI were analyzed by logistic regression.</p><p><b>RESULTS</b>The overall incidence rate of postoperative AKI was 13.78% (153/1 110), and the mortality rate was 2.52% (28/1 110). The mortality rate of children with AKI was 13.1% (20/153). The patients with hypoalbuminemia after surgery (≤35 g/L) accounted for 44.50% (494/1 110). Before and after propensity score matching, the hypoalbuminemia group had a significantly higher incidence of AKI than the normal albumin group (P<0.05). The children with AKI had a significantly lower serum albumin level after surgery than those without AKI (P<0.05). The multivariate logistic regression analysis showed albumin ≤35 g/L was one of the independent risk factors for postoperative AKI.</p><p><b>CONCLUSIONS</b>Albumin ≤35 g/L within 48 hours postoperatively is an independent risk factor for postoperative AKI in children after CPB surgery.</p>

Clinical characteristics and prognostic analysis of children with congenital heart disease complicated by postoperative acute kidney injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the perioperative clinical data of children with congenital heart disease complicated by acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery, and to explore potential factors influencing the prognosis.</p><p><b>METHODS</b>A retrospective analysis was performed among 118 children with congenital heart disease who developed AKI within 48 hours after CPB surgery.</p><p><b>RESULTS</b>In the 118 patients, 18 died after 48 hours of surgery. Compared with the survivors, the dead children had significantly higher incidence of cyanotic disease and Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) scores before surgery; during surgery, the dead children had significantly longer CPB time and aortic cross-clamping time, a significantly higher proportion of patients receiving crystalloid solution for myocardial protection, and a significantly higher mean blood glucose level. Within 48 hours after surgery, the dead children had significantly higher positive inotropic drug scores, significantly higher creatinine values, a significantly higher incidence of stage 3 AKI, a significantly higher proportion of patients receiving renal replacement the, and significantly higher usage of blood products (P<0.05). The mortality rate of the patients increased with increased intraoperative blood glucose levels (P<0.05). Patients with intraoperative blood glucose levels >8.3 mmol/L had a significantly lower postoperative cumulative survival rate and a significantly shorter mean survival time than those with blood glucose levels ≤ 8.3 mmol/L (P<0.05).</p><p><b>CONCLUSIONS</b>Intraoperative blood glucose levels are associated with the prognosis in children with congenital heart disease complicated by AKI after CPB surgery. Maintaining good intraoperative blood glucose control can improve the prognosis of the children.</p>

Comparison between volar and radial column approach by plate fixation for the treatment of unstable fracture of distal radius: a Meta-analysis / 中国骨伤

<p><b>OBJECTIVE</b>To assess the clinical effectiveness of volar and radial column approach by plate fixation for the treat- ment of unstable fracture of distal radius.</p><p><b>METHODS</b>According to Cochrane Systematic Review, Medline, Embase, Cochrane Li- brary, CNKI and CBM, randomised controlled trials (RCTs) of volar and radial column approach by plate fixation for the treat- ment of unstable fracture of distal radius were searched for from 1966 to 2014. Data analysis was performed with the Cochrane Collaboration's RevMan 5.0 software.</p><p><b>RESULTS</b>Totally 391 patients of 6 RCTs and 2 retrospective cohort studys were included and divided into volar plate group (187 cases) and radial column plate group (204 cases). Meta-analysis result showed: compared with radial column plate group, volar plate group had significant difference in recovery of wrist function [SMD = 0.74, 95% CI (0.47, 1.01), P < 0.00001], Gartland-Werley scores [SMD = -1.39, 95% CI (-2.24, -0.53), P = 0.001], postoperative neural in- jury [OR = 3.67, 95% CI (1.37, 9.84), P = 0.01 1 and postoperative wrist pain [OR = 0.32, 95% CI (0.13, 0.74), P = 0.008]. But no significant difference was identified in DASH scores [SMD = -0.36, 95% CI (-0.97, 0.26), P = 0.25], radiographic result assess- ment [SMD = -0.18, 95% CI (-0.53, 0.16), P = 0.3], postoperative grip strength [SMD = 0.71, 95% CI (-0.12, 1.54),P = 0.09], postoperative tendinous damage [OR = 0.31, 95% CI (0.10, 0.98), P = 0.05] and carpal tunnel syndrome [OR = 0.96, 95% CI (0.63, 1.48), P = 0.87].</p><p><b>CONCLUSION</b>Compared with radial column plate internal fixation, volar approach plate fixation for treat- ment of distal radius intra-articular fracture has advantage of recovery of joint functionand. However, the volar approach plate fix- ation was associated with a higher risk of long-term complications than the radial column approach plate fixation.</p>

HPLC determination of CPT-11 and its metabolite 7-ethyl-10 HCPT in incubation system of rat liver microsomes / 中国药学杂志

OBJECTIVE: To establish an HPLC method for determing irinotecan (CPT-11) and its metabolite 7-ethyl-10 HCPT in rat liver microsome incubation system, and to optimize the incubation conditions. METHODS: CPT-11and SN-38 were determined by HPLC. Single factor design was used to optimize the incubation conditions. RESULTS: The linear range of CPT-11 and 7-ethyl-10 HCPT in rat liver microsome incubation system were 20-4000 ng · mL-1 and 2-400 ng · mL-1, respectively. The optimal incubation conditions were as follows: 10 μmol · L-1 CPT-11, 0.02 mg liver microsomes and incubation for 15 min. CONCLUSION: The HPLC method is accurate and suitable for the determination of CPT-11and 7-ethyl-10 HCPT in rat liver microsomes. The incubation condition can be applied in drug interaction studies of irinotecan.

Determination of 5-hydroxylansoprazole/lansoprazole sulfone by HPLC-MS/MS in incubation system in vitro / 中国药学杂志

OBJECTIVE: To establish a HPLC-MS/MS method for determing 5-hydroxylansoprazole/lansoprazole sulfone, and optimize the incubated conditions for rat liver microsomes. METHODS: 5-Hydroxylansoprazole/lansoprazole were determined by HPLC-MS/MS. Single factor design was used to optimize the incubated conditions and the enzymes kinetics value was evaluated by graphical analysis with Lineweaver-Burk double reciprocal plots. RESULTS: The linear range of 5-hydroxy lansoprazole and lansoprazole sulphone in liver microsome incubation system were 5.57-2 520 and 5.42-2 480 ng · mL-1, respectively. The optimal incubated conditions were 10 μmol · L-1 lansoprazole, 0.16 mg liver microsomes, and 10 min incubation, respectively. CONCLUSION: The HPLC-MS/MS method is accurate and suitable for the determination of 5-hydroxy lansoprazole and lansoprazole sulfone in rat liver microsomes. The incubated condition can be applied for study in the drug interaction with lansoprazole.