ABSTRACT
Patients with advanced chronic liver disease （ACLD） are hospitalized due to hepatitis， acute decompensation or liver failure and its complications， and they often require stratified management due to different severities. The patients with acute－on－chronic liver failure （ACLF） have the highest short－term mortality rate among ACLD patients and should be treated in tertiary hospitals. Although non－ACLF patients tend to have a relatively low mortality rate， they still have the risk of progression to ACLF， and there is a significant increase in mortality rate after progression to ACLF， which requires stratified management. The patients with extremely low progression rates often have favorable clinical outcomes and can be administrated in primary hospitals， while the high－risk population should be closely monitored and timely transferred in case of disease progression. However， currently there is still a lack of accurate predictive models for evaluating the risk of progression to ACLF， and further studies are needed to find new biomarkers or algorithms.
ABSTRACT
The liver plays an important role in procoagulant and anticoagulant mechanisms in human body. There are complex changes in hemostasis in patients with liver cirrhosis, with the presence of interaction between the portal venous system and the peripheral system and differences in etiology, and such patients have a dual trend of hemorrhage and thrombosis. At present, there are certain limitations in coagulation function tests commonly used in clinical practice. The primary etiology and results of various coagulation tests should be considered before initiation of anticoagulant therapy for patients with liver cirrhosis, so as to make the best clinical decisions for patients.
ABSTRACT
OBJECTIVE：To optimize the f ormulation of docetaxel （DTX）-mPEG-PLGA-mPEG （PELGE）-nanoparticles （NPs），and to characterize it and evaluate its in vitro drug release and antitumor activity. METHODS ：PELGE were synthesized by ring-opening polymerization. DTX-PELGE-NPs were prepared by using emulsion solvent evaporation method. The content of DTX in DTX-PELGE-NPs was determined by HPLC. Box-Behnken design-response surface methodology was applied to optimize the formulation of the nanoparticles using the amount of DTX ，PELGE and poloxamer 188 as independent variable ，using entrapped efficiency as dependent variable. The particle size and Zeta-potential of DTX-PELGE-NPs were characterized by laser particle size analyzer and transmission electron microscope. The in vitro release of the DTX-PELGE-NPs was investigated by ultra-filtered centrifugation，using DTX injection as reference. In vitro cytotoxicity of the DTX-PELGE-NPs was investigated by MTT assay ， using DTX and PELGE-NPs without DTX as reference . RESULTS ：The optimal formulation included 2.80 mg DTX ，20.60 mg PELGE and 6％ poloxamer 188. The entrapped efficiency of optimized DTX-PELGE-NPs was （86.79±1.32）％；drug-loading amount was （10.21±0.78）％，and average particle size was （78.4±2.9）nm；polydispersity coeffici ent was （0.187±0.018）and Zeta potential was （－20.6±1.5）mV. Furthermore ，DTX- PELGE-NPs showed a regular spherical and uniform distribution under scanning electron microscopy. Compared with DTXinjection（accumulative release rate of 92.3％ at 4 h），DTX- PELGE-NPs had a significant sustained-release effect （accumu-lative release rate of 78.6％ at 36 h）. 0.1-50 μg/mL PELGE-NPs had no obvious cytotoxicity to human breast cancer cells MCF-7（P＞0.05）. 0.5-10 μg/mL DTX-PELGE-NPs could significantly inhibit the growth of human breast cancer cells MCF-7， and its inhibitory effect （except for DTX-PELGE-NPs 10 μg/mL group）was significantly stronger than that of DTX injection （P＜ 0.05）. CONCLUSIONS ：The optimized formulation is stable and feasible. The obtained DTX-PELGE-NPs not only have uniform particle size ，high encapsulation rate obvious slow-release effect ，but also have stronger anti-tumor effect in vitro than DTX injection.