OBJECTIVE:To evaluate the clinical efficacy of liraglutide and insulin glargine in the treatment of type 2 diabetes mellitus (T2DM) and conduct pharmacoeconomic analysis, and to provide economical and reasonable T2DM treatment plan. METHODS:80 T2DM patients were randomized into liraglutide group and insulin glargine group,with 40 cases in each group. Both groups were given Metformin hydrochloride sustained-release tablet orally 0.5-2.0 g/d,and diabetes mellitus diet and sport training guide after oral antidiabetic drug withdrawal of previous treatment plan. Liraglutide group was given Liraglutide injection hypodermically,0.6-1.2 mg,qd;insulin glargine group was given insulin glargine hypodermically at 22 o’clock,initial dose of 0.2 IU/(kg·d),adjusted according to the levels of PG,FBG,nocturnal blood glucose level till FBG≤7 mmo1/L and 2 h PG ≤10 mmol/L in both group. Treatment course of 2 groups lasted for 12 weeks. The changes of FBG,2 h PG,HbA1c and BMI were ob-served in 2 groups before and after treatment. 2 therapy plans were evaluated and compared by cost-minimization analysis. RE-SULTS:After treatment,the levels of FBG,2 h PG and HbA1c decreased significantly in 2 groups,compared to before treatment, with statistical significance (P<0.05),but there was no statistical significant difference between 2 groups (P>0.05). After treat-ment,BMI of liraglutide group decreased significantly compared with before treatment and insulin glargine group,with statistical significance (P<0.05). There was no statistical significant difference in BMI of insulin glargine group before and after treatment (P>0.05). Cost-minimization analysis showed that the cost of insulin glargine group in reducing FBG,2 h PG and HbA1c were less than liraglutide group,but were more than liraglutide group in reducing BMI. Sensitivity analysis demonstrated the stability and reliability of cost-minimization analysis. CONCLUSIONS:Lira-glutide and insulin glargine have the same clinical efficacy,but insulin glargine need lower cost in blood glucose control,and liraglutide is better therapy plan for body weight control.

ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L^-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe²⁺ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot. ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）. ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe³⁺ uptake， leading to an imbalance in the antioxidant system.

Paridis Rhizoma possesses the functions of clearing heat and detoxifying， alleviating swelling and relieving pain， cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer， lung cancer， gastric cancer， and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation， migration， and invasion of tumor cells， regulating cell cycle， inducing apoptotic and non-apoptotic death pathways， and regulating metabolism and tumor microenvironment. Furthermore， total saponins in Paridis Rhizoma showed anti-inflammatory， antioxidant， antimicrobial， hemostatic， and uterus-contracting activities. At the same time， they may induce apoptosis of normal cells， inflammation and oxidative stress， and metabolic disorders. In recent years， the reports of liver injury， reproductive injury， gastrointestinal injury， hemolysis， and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate， while oral administration may have hepatoenteric circulation. Meanwhile， due to the low solubility and activation of P-glycoprotein （P-gp） molecular pump， the prototype absorption， intestinal permeability， and recovery rate of total saponins in Paridis Rhizoma are poor， which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect， pharmacokinetics， and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure （CNKI）， VIP， and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords， hoping to provide references for the research， development， and clinical application of such components.