Objective:To analyze the off-label use and adverse reactions of lobaplatin for injection to provide reference for the rational use in clinic. Methods:A retrospective review was conducted on the inpatient medical records (201 cases) with lobaplatin for injection from November 2016 to July 2017 in a hospital and analyzed the characteristics of adverse drug reactions/events (ADR/ADE) with the help of SPSS software. The ADRs were performed correlation factor analysis.Results:The off-label ratio of the indication,administration route and solvent for lobaplatin was 89.55%,18.41% and 47.26%,respectively. The rate of adverse events was 63.18%. The main adverse reactions were blood and lymphatic system disorders and hepatobiliary system damage,and the manifestations were lymphocyte decrease(40.80%),hemoglobin(23.88%),white blood cell decrease (19.90%) and platelet decrease (15.92%) and AST increase (10.45%). No grade 5 adverse event happened, however, new adverse reactions,such as palpitation, dyspnea, harshness, etc were shown. The use of 0.9% sodium chloride injection as the solvent for lobaplatin may be a risk factor for ADRs. Conclusion:Most of the medical orders with lobaplatin for injection contain off-label use,and the rate of adverse events is as high as 63.18%. The use of 0.9% sodium chloride injection as the solvent for lobaplatin may be a risk factor for ADRs.

ABSTRACT Ellagitannin is a complex compound of plant polyphenols, and it is an effective substance in many commonly used natu-ral drugs. Ellagitannin has been widely used in medicine, cosmetics, food, health care products and the other fields. The article re-viewed the structure source, biological activity and metabolic outcomes of ellagitannin in order to provide basis for the in-depth resear-ches and the resource development of natural medicines rich in tannins.

ABSTRACT Ellagitannin is a complex compound of plant polyphenols, and it is an effective substance in many commonly used natu-ral drugs. Ellagitannin has been widely used in medicine, cosmetics, food, health care products and the other fields. The article re-viewed the structure source, biological activity and metabolic outcomes of ellagitannin in order to provide basis for the in-depth resear-ches and the resource development of natural medicines rich in tannins.

Objective:To investigate the transport mechanism of punicalagin in MDCK monolayer model .Methods:The safe con-centration of punicalagin in MDCK cells was determined by CCK8 assay.Millicell -ERS was used to measure cell monolayer TEER value to determine the integrity of the cell monolayer .The effects of direction , drug concentration , time, P-gp inhibitor and EDTA-Na2 on the absorption and transport of punicalagin were studied systematically .And then the drug concentration was analyzed by HPLC to calculate the apparent permeability coefficient (Papp) and efflux ratio(ER).Results: Punicalagin transport in MDCK cells was time and concentration dependent .Punicalagin showed poor absorption in MDCK cells .Papp from apical to basolateral side ( AP-BL) within the concentration range of 100-300μg· ml-1 was (6.13 ±0.12) ×10 -7 cm· s-1 , (6.96 ±0.26) ×10 -7 cm· s-1 and (5.94 ±0.10) ×10 -7 cm· s-1 , respectively .P-gp inhibitor and EDTA-Na2 could significantly increase the transport of punicalagin in AP-BL direc-tion, while the transport decreased at 4℃.Conclusion:The transport mechanism of punicalagin might be passive diffusion as the dom-inating process involving active transportation .Punicalagin is one of P-gp substrates with exocytosis and absorbed via the paracellular route.

Objective:To investigate the effects of neferine on the proliferation and apoptosis of HepG2 cells. Methods: The effect of neferine on the proliferation of HepG2 cells was determined by cell counting kit-8 (CCK-8), the morphology of HepG2 cells with Hoechst33258 staining was observed under a fluorescent microscope,the degree of damage to HepG2 cells was observed by lactate dehydrogenase (LDH) kit,Annexin V /propidium iodide (PI) and PI/Rnase were used to analyze the apoptosis and the cell cycle. Results:Neferine could inhibit the proliferation of HepG2 cells in a dose and time-dependent manner,and the degree of damage to the cell membrane increased with the dose of the drug. The results of Hoechst33258 staining and flow cytometry (FCM) indicated that HepG2 cells were arrested in G0/G1phase and the apoptotic rate increased with the concentration increase of neferine.Conclusion:Neferine can inhibit the growth and proliferation of HepG2 cells in a dose and time-dependent manner, induce it arrested in G0/G1 phase and induce the late apoptosis of HepG2 cells.

Objective:To optimize the formula and preparation of exendin W /O/W multiple emulsion , and study the main proper-ties in vitro to lay foundation for the development of exendin prolonged action preparation .Methods:Using multiple emulsion yield and centrifugal separation time as the comprehensive index , the formula and preparation of exendin multiple emulsion were optimized by or-thogonal tests, and the morphology, particle size, stability, encapsulation efficiency and drug release in vitro were studied.Results:The optimal formula was as follows:the volume ratio of W1 phase to O phase was 1:1.2, the quality percentage of emulsifierⅠin the O phase was 10％, poloxamer 407 in W2 phase was 10％, and the quantity ratio of W1/O to W2 phase was 1:1.The optimal prepara-tion conditions were as follows:the stirring speed for W1/O was 10000 r· min-1 , and the stirring time was 10 min, and that for W1/O/W2 was 2500 r· min-1 with the stirring time of 3 min.The multiple emulsion was spherical with the mean size of (46.3 ±2.6)μm, and the centrifugal and viscosity stability were both promising .The drug encapsulation efficiency was above 90％, and the drug release in vitro accorded with a Higuchi equation: Y=13.7930X+5.5981(r=0.9883), showing notable sustained and prolonged property .Conclusion:The optimal formula and preparation process of exendin multiple emulsion are simple with high drug content , good stability and notable sustained release property in vitro.

Objective:To improve the stability of exendin W/O/W multiple emulsion.Methods:The amount of electrolyte sodium chloride in the internal water phase and that of thickener PVP in the external water phase were both screened for exendin W/O/W mul-tiple emulsion,and the cryoprotectant in the freeze-drying process was optimized in order to further optimize the formula and preparation of exendin W/O/W multiple emulsion. Verification experiment was carried out to study the main properties of the optimized exendin W/O/W multiple emulsion in vitro. Results: The optimal quality volume percentage concentration of sodium chloride in the internal water phase was 0.10%,and that of PVP in the external water phase was 0.15%,and the best cryoprotectant was 10% mycose. The main in vitro properties of exendin W/O/W multiple emulsion showed no significant changes before the freeze-drying and after the rehy-dration. Conclusion:Through the optimization of the internal and external water phase of exendin W/O/W multiple emulsion,the sta-bility is enhanced,which lays foundation for the in vivo studies.

In recent years, a considerable number of studies have shown that N-acetylcysteine( NAC) is a promising agent in the treatment of a variety of neuropsychiatric disorders. The present article briefly outlined its role in the regulation of these disorders and reviewed the current literatures on the use of NAC in autism and obsessive-compulsive related disorders(OCRD)in order to provide ba-sis for the clinical application of NAC in neuropsychiatric field.

Gastroesophageal reflux disease is a common disease of digestive system. With the increase of domestic morbidity, the burden on the medical and health care system is correspondingly increased. The treatments of gastroesophageal reflux disease are mainly drug therapy and surgical treatment. With the increase in the number of selectable drugs and the emergence of new surgical techniques, it is particularly necessary to consider pharmacoeconomics of the plan while ensuring safety and effectiveness, especially in the context of the lack of overall medical and health resources in the country. The study of pharmacoeconomics considers different prevention, diag-nosis and treatment strategies from the perspective of economics, and provides reference for clinical treatment decision. The article re-viewed recent advances in pharmacoeconomics evaluations of gastroesophageal reflux disease.

Objective To observe the effects of sulforaphane on the apoptosis in human gastric cancer HGC27 cells, and to study the possible mechanism of it. Methods The proliferation activity of HGC27 cells treated with sulforaphane was analyzed by CCK8 kit. Apoptosis rates were assessed by flow cytometry. After HGC27 cells were treated with sulforaphane, and the expression levels of Bcl-2, Bax, caspase-3, PI3K, Akt and p-Akt were measured by Western Blot. After HGC27 cells were treated with LY294002, sulforaphane and LY294002+sulforaphane, the expression levels of PI3K, Akt and p-Akt were also investigated by Western Blot. Results The proliferation of HGC27 cells was significantly suppressed by sulforaphane in dose-dependent and time-dependent manners. The apoptotic rates of HGC27 cells in 10, 20, 40 μg/ml of sulforaphane groups (10.29% ± 1.57%, 23.68% ± 1.69%, 35.29% ± 2.38% vs. 2.52% ± 0.74%) were greatly increased compared with the control group. The expression levels of Bax (18.92 ± 2.18, 34.06 ± 5.06, 44.08 ± 5.69 vs. 12.51 ± 2.15) in 10, 20, 40 μg/ml of sulforaphane groups were greatly increased compared with control group(P＜0.05). The expression levels of Bcl-2 (56.39 ± 5.27, 33.06 ± 4.26, 25.61 ± 4.01 vs. 78.25 ± 7.26), PI3K (51.06 ± 5.27, 42.06 ± 5.21, 23.08 ± 4.51 vs. 79.07 ± 8.12), p-Akt/Akt (58.62 ± 5.34, 35.24 ± 4.06, 14.52 ± 2.56 vs. 82.64 ± 8.25) in 10, 20, 40 μg/ml of sulforaphane groups were greatly decreased compared with control group (P＜0.05). The expression levels of PI3K (56.41 ± 5.36, 34.37 ± 4.52, 23.11 ± 3.05 vs. 81.24 ± 7.16), p-Akt/Akt (49.52 ± 5.84, 31.06 ± 4.09, 21.05 ± 2.28 vs. 77.52 ± 7.06) in the LY294002, sulforaphane and the LY294002+sulforaphane groups were greatly decreased compared with the control group (P＜0.05). Conclusions Sulforaphane may inhibit proliferation and promote apoptosis of HGC27 cells probably by inactivating PI3K/Akt signaling pathway.