AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.

AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics， surgery， radiotherapy， or hormone therapy. The treatment process has limitations such as multidrug resistance， non-selective targeting of cancer cells， and drug toxicity. With the development and application of traditional Chinese medicine （TCM）， Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation， differentiation， and metastasis， and avoid drug resistance， serving as the focus of current tumor treatment research. Hedysari Radix， one of the genuine medicinal materials in Gansu province， is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation， immune regulation， anti-oxidation， prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties， Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity， scavenging free radicals， and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer， bladder cancer， gastric cancer， breast cancer， and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research， this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis， blocking cell cycle， inhibiting tumor cell proliferation， migration， and invasion， regulating micro mRNA （miRNA）， inducing cell autophagy， enhancing immune regulation， as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics， and systematically explained the anti-tumor mechanism of Hedysari Radix active components， aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

OBJECTIVE: To compared the effect of different drying methods on drying characteristics, water effective diffusion coefficient and biased activation energy of Codonopsis Radix and to definite 3 different drying methods of varying temperature(45-55-60, 60-55-45, 60-45-60℃) and 3 constant temperature(45, 55, 60℃) on drying characteristic curves of different commercial grades of Codonopsis Radix. METHODS: Used R2, χ2 and RMSE as evaluation indexes, 10 typical drying kinetic models were selected to fit the drying curve of Codonopsis Radix, and the effective moisture diffusion coefficient and biased activation energy under different drying method were calculated. RESULTS: It was found that the Midilli model could well describe the drying process of different commercial grades of Codonopsis Radix, the water ratio of Codonopsis Radix showed an exponential downward trend. If the initial drying temperature was set above 55℃, the maximum drying rate could be reached within 2 h. And commercial grades temperature had certain influence on the effective water diffusion coefficient of Codonopsis Radix. Under the same temperature condition, the average speed of moisture migration during drying of Codonopsis Radix was:first-class> second-class>third-class, and the Deffwere 10.433 9×10-8, 5.545 2×10-8, 2.249 6×10-8·m2·s, respectively. The calculated bias activation energy of Codonopsis Radix was 2.943×104-4.378×104 J·mol-1, the order of bias activation energy of different drying methods was as follows:60-55-45℃ variable temperature<60-45-60℃ variable temperature<45-55-60℃ variable temperature<55℃ constant temperature<60℃ constant temperature <45℃ constant temperature, which indicated that the moisture in the medicinal materials was more likely to evaporate and overflow and consumes less energy than the constant temperature drying. In particular, the bias activation energy of 60-55-45℃ drying method was 77.54% and 81.86% of the other 2 variable temperature drying methods, which were 67.22%, 75.13% and 74.26% of the 3 kinds of constant temperature drying. CONCLUSION The use of cooling mode in the drying process can save more time and energy, and can provide experimental basis for the improvement of drying technology and optimization of drying process of Codonopsis Radix.

OBJECTIVE：To p rovide policy suggestions for the development and supervision of online drugstores in China. METHODS：By literature review ，the relevant literatures and policy documents about the development of online drugstores were searched，screened and sorted out to summarize the development process of China ’s internet drug trading mode and policy ，analyze the development status of China ’s online drugstores ；on the basis of the development experience of some developed countries ，the suggestions were put forward for China ’s relevant policies. RESULTS & CONCLUSIONS ：China’s medical e-commerce started relatively late ，and the policies related to online drug trading were basically released during last 20 years. The number of online drugstores showed a growing trend. The online drugstores were geographically allocated widely but unevenly. They sold many varieties，and policies on selling prescription medicines were gradually liberalized. These online drugstores provided diverse payment and delivery choices ，but their pharmaceutical service needed to be improved. The development models of online drugstores in the United Kingdom ，the United States and Germany could be referred. According to the current situation of online drugstores in China ， combined with the development mode and operation strategy in foreign countries ，it is suggested to improve relevant laws and regulations，and strengthen legal support ；strengthen the government supervision to ensure drug safety ；use the industrial power to standardize medicine operation behavior ；set up the third part trading platform to promote medical insurance payment.

Objective To investigate the influencing factors and clinical significance of high-resolution magnetic renounce imaging (HR-MRI) plaque enhancement in patients with symptomatic intracranial atherosclerotic (ICAS) stenosis.Methods Patients with symptomatic ICAS stenosis confirmed by digital subtraction angiography and examined by HR-MRI were enrolled prospectively.The demographic data,vascular risk factors,laboratory tests,and imaging features of plaques were compared according to whether the plaques were enhanced or not.They were randomly divided into an ischemic stroke group and a transient ischemic attack (TIA) group according to the results of diffusion-weighted imaging.The relationship between plaque enhancement and ischemic stroke was analyzed.Results Thirty-fiwe patients with symptomatic ICAS stenosis were enrolled.Their mean age was 53 ± 13 years and 25 were males.There were 21 patientswith ischemic stroke and 14 patients with TIA;22 had plaque enhancement and 13 did not have.The leukocyte count ([7.50±2.30] × 109/L vs.[5.80± 1.00] × 109/L;t=2.487,P=0.018) and proportion of severe stenosis (86.4％ vs.53.8％;P =0.040) of the plaque enhancement group were significantly higher than those of the non-enhancement group.The proportion of smoking was significantly lower than the non-enhancement group (13.6％ vs.46.2％;P=0.050).The plaque enhancement rate of the ischemic stroke group was higher than that of the TIA group (71.4％ vs.50.0％;P =0.288),but there was no significant difference.Conclusions In patients with symptomatic ICAS,the degree of vascular stenosis and the leukocyte level were associated with plaque enhancement.In addition,there was no significant correlation between plaque enhancement and the occurrence of ischemic stroke in patients with symptomatic ICAS.

Objective To evaluate cerebral perfusion through brain computed tomography perfusion imaging (CTP) in order to investigate the relationship between cerebral perfusion and vascular cognitive impairment (VCI).Methods A total of 103 patients with ischemic stroke were recruited, who received thrombolytic therapy and CTP test in the Fourth Affiliated Hospital of China Medical University from December, 2016 to May, 2017. The patients were divided into normal cognitive function group (control group, n=43), vascular cognitive impairment-no dementia group (VCIND group, n=48), and vascular dementia group (VD group, n=12) according to the degree of impairment in cognitive function after the assessment of Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). The characteristics of cerebral blood flow perfusion in region of interest of brain CTP were analyzed.Results There was difference in incidence of diabetes among three groups (χ2=7.556, P<0.05). The rate of diabetes was higher in VCIND group and VD group than in the control group. Age and diabetes were the independent risk factors for VCI (OR>1, P<0.05). There was difference in cerebral blood volume (CBV) in frontal lobe, temporal lobe, and parietal lobe among three groups (F>3.216, P<0.05). CBV in frontal lobe, temporal lobe, and parietal lobe reduced in VD group than in the control group (P<0.05), while CBV in frontal lobe and temporal lobe reduced in VD group than in VCIND group (P<0.05). There was difference in mean transit time (MTT) in left temporal lobe, left parietal lobe, and centrum semiovale among three groups, while there was difference in left occipital lobe in time to peak (TTP) among three groups (F>3.116, P<0.05). MTT and TTP were higher in VD group than in the control group and VCIND group (P<0.05). There was no difference in cerebral blood flow (CBF) in both left and right brain, and MTT and TTP in right brain among three groups (P>0.05). CBV in frontal lobe, parietal lobe and right temporal lobe demonstrated positive relationship with the scores of MMSE (r>0.203, P<0.05). CBV in parietal lobe and left frontal lobe also demonstrated positive relationship with the scores of CDT (r>0.214, P<0.05).Conclusion The cerebral blood flow perfusion reduced in different levels of VCI, especially in frontal lobe, temporal lobe and parietal lobe. Cerebral blood flow perfusion reduced with the progress of cognitive impairment, and the left hemisphere injured earlier than the right one. Brain CTP may be applied in the early recognition of VCI.

Hypoxia inducible factor-1αis a kind of hypoxia response factor. Acute cerebral ischemia and anoxia can induce up-regula-tion of hypoxia inducible factor-1α, and the downstream genes, which plays a role in both the energy metabolism and collateral circulation after cerebral ischemia. Neural stem and progenitor cells regeneration also benefit the functional outcome after ischemic stroke. Hypoxia in-ducible factor-1αmay induce proliferation and differentiation of neural stem and progenitor cells through Notch, Wnt/β-catenin pathways, etc., in the ischemic stroke model.

ObjectiveTo compare the quality of Baitiao Codonopsis Radix with different commercial grades; To provide the basis for the rational utilization of Codonopsis Radix.MethodsTotally 54 batchs of Baitiao Codonopsis Radix with different commercial grades from main producing areas in Gansu were collected. The contents of lobetyolin and atractylenoideⅢ in Codonopsis Radix were detected by HPLC. Colorimetric method was used to detect the content of polysaccharide in the Codonopsis Radix. Chinese Pharmacopoeia 2010 Edition was referred to detect the content of extractum. One way ANOVA and factor analysis method were used to comprehensively evaluate the data.ResultsLobetyolin and atractylenoideⅢ were all negatively correlated with commercial grades. The results of the principal component factor ranking showed that the samples were not sorted by the order of commercial grades, with commercial grade two ranking in the forefront.Conclusion The quality of Baitiao Codonopsis Radix with different commercial grades is different, and the quality of commercial grade two is better than other commercial grades.