ObjectiveTo explore the possible mechanism of action of Lifei Xiaoji Pill （理肺消积丸， LXP） in the treatment of non small cell lung cancer based on the Warburg effect and the USP47/BACH1 pathway. MethodsFifty C57BL/6 mice were randomly divided into five groups， model group， LXP group， inhibitor group， LXP + inhibitor group， and cisplatin group， with 10 mice in each group. A lung cancer mouse model was established by subcutaneously injecting Lewis cells. On the next day， the model group mice were given 0.2 ml of saline by gavage daily， the LXP group given 240 mg/（kg·d） of LXP solution once a day by gavage， the inhibitor group intraperitoneally injected with P22077 at a dose of 10 mg/（kg·d） every day， the LXP + inhibitor group given both LXP by gavage and P22077 by intraperitoneal injection once a day， and the cisplatin group received 0.5 mg/（kg·d） cisplatin intraperitoneally every other day. All treatments lasted for 14 days. On the day after the last dose， tumor weight and volume were measured， tumor histopathology was examined by HE staining， apoptosis in tumor tissues was detected by TUNEL staining， and proliferation cell nuclear antigen （PCNA） protein levels were detected by immunohistochemistry. Warburg effect indicators， including glucose concentration， lactate content， and adenosine triphosphate （ATP） production in tumor tissues， were measured. Western Blot and qRT-PCR were used to detect the protein and mRNA expression levels of USP47， BACH1， hexokinase 2 （HK2）， and glyceraldehyde 3-phosphate dehydrogenase （GAPDH）. ResultsCompared with the model group， all drug intervention groups showed reduced tumor weight and volume， improved tumor pathology， decreased PCNA positive rate， increased apoptosis rate， and reduced expression levels of USP47， BACH1， and HK2 proteins and mRNA （P＜0.05 or P＜0.01）. Except for lactate content in the cisplatin group， the glucose concentration in tumor tissues of other drug intervention groups increased， while lactate content and ATP production decreased （P＜0.05 or P＜0.01）. Compared with the LXP group， the LXP + inhibitor group showed more significant improvements in these indicators （P＜0.05 or P＜0.01）. Compared with the cisplatin group， the LXP + inhibitor group had lower mRNA expression of HK2 and GAPDH， and lower protein levels of USP47 and HK2 （P＜0.05 or P＜0.01）. Compared with the inhibitor group， the cisplatin group had higher HK2 protein levels， while the LXP + inhibitor group showed lower mRNA expression of BACH1， HK2， and GAPDH （P＜0.05 or P＜0.01）. ConclusionLXP significantly inhibits tumor growth in lung cancer mice， and its mechanism of action may be related to inhibiting the Warburg effect via the USP47/BACH1 pathway.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

OBJECTIVE To establish the de tection method for the adulteration of Bupleurum marginatum in Ganmao qingre granules，and to determine the adulteration limit . METHODS HPLC-MS/MS method was used to detect the content of nepasaikosaponin K in commercial and self -made samples of Ganmao qingre granules ，using electrospray ionization ，and the analysis was carried out under multiple reaction monitoring model in negative mode with m/z 943.6→635.5 as the quantitative ion pair. The calculation method was established for the adulteration proportion of B. marginatum in Ganmao qingre granules . Taking nepasaikosaponin K as the index ，the adulteration limit was determined . RESULTS The linear range of nepasaikosaponin K were 0.051-20.200 μg/mL（r＝0.999 1）. RSDs of precision ，repeatability and stability （24 h）tests were all lower than 2.50%. The average recoveries were 97.58%（RSD＝2.09%，n＝9）. The limit of detection was 0.60 μg/g，the limit of quantitation was 1.80 μg/g. The adulteration ratio of B. marginatum in Ganmao qingre granules had a good linear relationship to the peak area of nepasaikosaponin K in the range of 5%-100%（r＝0.990 9）. The contents of nepasaikosaponin K in 15 batches of Ganmao qingre granules were 2.584-56.661 μg/g. One batch of samples exceeded the proposed adulteration limit （10%），and the unqualified rate was 6.67%. CONCLUSIONS The established analytical method can be used to detect the adulteration of B. marginatum in Ganmao qinggre granules ，the proposed adulteration limit is 10%.

Objective To observe the effects of foam dressings on preventing medical device related pressure injuries in patients with neck fixation.Methods Totally 156 patients who received neck fixation in Xingtai People's Hospital between January and June 2017 were selected and equally randomized into the towel group,the hydrocoiloid group and the foam dressing group (n=52) depending on different protective materials used on the interface between neck fixation and skin.The incidence and severity of local pressure injuries on the neck and the auricle were compared between the three groups.Results There were no phase-2 local pressure injuries on the neck or the auricle in any patient in the three groups;the incidences of pressure injuries in the foam dressing group,the towel group and the hydrocolloid group were 15.38％,56.60％ and 41.18％,respectively (x2=20.008,P ＜ 0.001).Conclusions Foam dressings can effectively prevent the incidence of medical device related pressure injuries in patients with neck fixation.

BACKGROUND:Endothelial progenitor cels are widely used in the treatment of various vascular diseases, and early exercise training contributes to restore motor function after spinal cord injury. However, the therapeutic effects of endothelial progenitor cel transplantation or early exercise training alone are unfavorable. OBJECTIVE:To observe the influence of transplantation of endothelial progenitor cels combined with early exercise training on blood vessel regeneration and hind limb function in rats after spinal cord injury. METHODS:Eighty adult Sprague-Dawley rats were enroled to establish spinal cord injury models using the modified Alen’s method, and then randomly divided into four groups. Rats were respectively given culture mediumvia the tail vein, injection of endothelial progenitor cels (3×106)via the tail vein, roler and treadmil trainings for 2 weeks, or injection of endothelial progenitor celsvia the tail vein folowed by 2 weeks of roler and treadmil trainings in the model, cel transplantation, exercise and combined groups. RESULTS AND CONCLUSION:At 2 weeks after transplantation, the hindlimb motor function of rats in the combined group was better than that in the cel transplantation group and exercise group, and moreover, the percentage of CM-Dil positive cels, the number of horseradish peroxidase-positive nerve fibers, capilary density and expression of vascular endothelial growth factor and brain-derived neurotrophic factor were also significantly higher in the combined group than the cel transplantation group and exercise group. These findings indicate that early exercise training has a neuroprotective role in spinal cord injury; endothelial progenitor cel transplantation combined with early exercise training can promote regeneration of synapses and blood vessels and improve hindlimb motor function of rats, probably by increasing expression levels of vascular endothelial growth factor and brain-derived neurotrophic factor.

OBJECTIVETo prepare the submicron emulsion of fresh Zhongjiefeng volatile oil.

METHODThe Zhongjiefeng volatile oil submicron emulsion was obtained after passing the elementary emulsion through a high pressure homogenizer. The physical and chemical stability of the emulsion was evaluated with the stability parameter of centrifugation, appearance of emulsion and the pH. The formulation and processing factors were optimized by single factor reviewing and orthogonal experimental design.

RESULTBy controlling various processing factors and optimizing formulation, the stable submicron emulsion of Zhongjiefeng volatile oil was prepared. Its mean particle diameter was 164-169 nm with PDI 0.084-0.107 and Zeta electric potential was -40 mV.

CONCLUSIONThe formulation and preparation technique of the emulsion is reasonable.

Objective To evaluate the changes of platelet-derived growth factor(PDGF) and vascular endo-thelial growth factor(VEGF) in infectious and autoimmunity diseaases. Methods The growth factors were measured by ELISA in 149 patients for seven times in different periods,and the levels and duration were compared. Results PDGF was (6.32±2.54) μg/ml and (2.57±1.65) μg/ml (P<0.05), and VEGF was (179.5±53.30) ng/ml and (221.4±70.04) ng/ml(P<0.05) in the two groups before treatment;There was statistical significance in dif-ferent time points between groups and within groups for PDGF(P<0.05) and significant difference for time chan-ging to the peak and changed duration between two groups for VEGF(P<0.05). For the two groups,the peak time of PDGF were (2.6±1.1) and (5.4±3.3) days;The peak time of VEGF were (2.4±0.7) and (7.2±3.3) days respectively(P<0.05 for each). However in the two groups, the change duration were (6.7±3.1) and (15.4±6.1) days for PDGF and (8.1±3.4) and (16.7±7.2) days for VEGF (P<0.05 for each). Conclu-sions There is significant difference for serum levels of PDGF and VEGF and the level change duration as well in the two groups, which maybe correlated with inflammatory nature and outcome.

AIM: To study the pharmacokinetics of ligustilide in the volatile oil from Angelica Sinensis(Oliv.) Diels in the rabbit. METHODS: HPLC method for ligustilide determination in the blood was developed.The HPLC system consisted of C_(18) column using MeOH-H_2O(65∶35,v/v) as mobile phase at a flow rate of 1.0 mL/min and UV detection at 236 nm. RESULTS: Linear calibration curves were obtained over the concentration range of 0.40 ?g?mL~(-1)～10.00 ?g?mL~(-1) for ligustilide.The minimum limit detection was 0.40 ?g?mL~(-1).The recovery of ligusitilide in blood was 90.90% with RSD 2.74%. CONCLUSION: After oral administration of volatile oil,intracorporal process of ligustilide in rabbit accords with 2-compartment model with 1 st order absorption,(2.6638) h and 108.88 h are obtained as t_(1/2?) and t_(1/2?) respectively.