OBJECTIVE To explore and predict the quality markers （Q-markers） of Compound xiebai capsules for the treatment of chronic obstructive pulmonary disease （COPD） by constituents analysis combined with network pharmacology and molecular docking studies， and to establish the quality standard of Compound xiebai capsules. METHODS UHPLC-TOF-MS was used for qualitative analysis of Compound xiebai capsules， and the candidate Q-markers of Compound xiebai capsules were screened by combining network pharmacology and molecular docking technology. Further， HPLC was applied to establish the fingerprints of 15 batches of Compound xiebai capsules and to conduct quantitative analysis of the main components. RESULTS A total of 51 components were identified from Compound xiebai capsules. Among them， 15 components， namely oxyberberine， methylworenine， coptisine， tetrahydroberberine， epiberberine， berberine， magnoflorine， gandensin， cucurbitacin D， hydroxygenkwan， jatrorrhizine， columbamine， quercetin， cucurbitacin R， and palmatine， were determined as the candidate Q-markers for Compound xiebai capsules in the treatment of COPD. A total of 13 common peaks were calibrated in the fingerprints of 15 batches of Compound xiebai capsules for COPD treatment， with similarity values ranging from 0.976 to 0.999 compared to the reference fingerprint. Seven components were identified among these peaks， namely peak 5 （magnoflorine）， peak 8 （jatrorrhizine）， peak 9 （epiberberine）， peak 10 （columbamine）， peak 11 （coptisine）， peak 12 （palmatine）， and peak 13 （berberine）. Their respective contents were （0.267±0.048）， （0.453±0.084）， （0.572±0.160）， （0.392±0.074）， （1.076±0.273）， （1.477±0.271）， and （6.664±1.249） mg/g （ n ＝3）. CONCLUSIONS This study predicted 15 candidate Q-markers of Compound xiebai capsules in the treatment of COPD and established the fingerprint along with a quantitative determination method for seven major components.

OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group， negative control group， positive control group （fluoxetine 10 mg/kg， i.g.）， single drug group （C. saxicola total alkaloids 210 mg/kg， i.g.） and combined drug group （C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg， i.g.） according to the random number table method， with 6 rats in each group. By lipopolysaccharide （LPS） induction modeling， except blank control group （no model and no administration） received intraperitoneal injection of the same amount of normal saline， the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling， each administration group was given relevant drug intragastrically according to the corresponding dose， and blank control group and negative control group （without drug treatment） were administered intragastrically with an equal volume of solvent to dissolve the drug； continued modeling while administering the drug. After two weeks of continuous administration， the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments； the levels of tumor necrosis factor-α， interleukin-1β and interleukin-6 in rats were determined； the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day， and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted， the area under the curve （AUC） was calculated， and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats.

ObjectiveTo investigate the pharmacodynamics， pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide（LPS）-induced depression rats. MethodRats were randomly divided into the control group， model group， fluoxetine group（10 mg·kg^-1）， Jiaotaiwan group（1.5 g·kg^-1） and combination group（1.5 g·kg^-1 of Jiaotaiwan+0.05 g·kg^-1 of borneol）， with 8 rats in each group. Except for the control group， the depression model was established by intraperitoneal injection of LPS for 7 consecutive days， and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors［interleukin-1β（IL-1β）， IL-6 and tumor necrosis factor-α（TNF-α）］ of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin（HE） and Nissl staining. After the behavioral tests of sucrose preference， open field and forced swimming were completed， blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage， the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed， and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group， rats in the model group showed decreased sucrose preference rate and total distance of open field， prolonged swimming immobility time， and increased expression of inflammatory factors in serum（P<0.01）. Compared with the model group， the sucrose preference rate and total distance of open field were increased， and the swimming immobility time was shortened in the rats of each administration group， and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group（P<0.05， P<0.01）. The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group， the area under the curve（AUC_0-t， AUC_0-∞）， peak concentration（C_max） and the average steady-state plasma concentration（C_av） of berberine and epiberberine in the combination group were increased（P<0.05， P<0.01）， AUC_0-t， AUC_0-∞， mean residence time（MRT_0-∞） and C_av of coptisine were significantly increased（P<0.05， P<0.01）， C_max of jatrorrhizine increased significantly（P<0.05）， but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group， the contents of jatrorrhizine， epiberberine， coptisine， palmatine and berberine in the brain tissue of combination group were increased（P<0.05， P<0.01）， the content of magnoflorine increased and that of berberrubine decreased， but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats， reduce the levels of serum inflammatory factors， improve the pathological damage of hippocampus， and have antidepressant effect. Compared with Jiaotaiwan alone， the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats， improve its bioavailability， promote its absorption， and improve the brain targeting of the drug， which is more conducive to the antidepressant effect of Jiaotaiwan.

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

Objective To investigate whether Danhong injection can enhance the therapeutic effect of neural stem cell (NSC) transplantation in repairing cerebral ischemia injury by regulating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Methods Forty male SD rats were randomly divided into the NSC transplantation group (NSC group), Danhong injection group (DH group), NSC+ Danhong injection group (N+D group), NSC+ Danhong injection group +ML385 group(N+D+M group) and PBS control group (PBS group), 8 rats in each group. All rat models of cerebral ischemia were established by embolization of the middle cerebral artery. Reperfusion was performed at 1.5 h after embolization. All rats in each group received corresponding interventions at 3 d after reperfusion. The neurological function score was evaluated before and 1, 2, 4 weeks after NSC transplantation. All rats were sacrificed at 4 weeks after NSC transplantation. The parameters related to oxidative stress were detected. The expression levels of neuron-specific nuclear protein (NeuN) and von Willebrand factor (vWF) were determined by immunofluorescence staining. Results Before NSC transplantation, the neurological function scores did not significantly differ among different groups (all P > 0.05). At postoperative 1, 2 and 4 weeks, the neurological function scores in the NSC, DH and N+D groups were significantly lower than those in the PBS and N+D+M groups (all P < 0.05). Compared with the PBS and N+D+M groups, the malondialdehyde (MDA) levels were significantly decreased, whereas the superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels were considerably increased in the NSC, DH and N+D groups (all P < 0.05). The GPX level in the N+D+M group was significantly lower than that in the PBS group (P < 0.05). Immunofluorescence staining showed that the transplant NSC in the rat brain migrated to the surrounding area of cerebral infarction and survived, and expressed neuronal marker NeuN and neovascularization marker vWF. However, the number of living NSC in the N+D+M group was significantly lower compared with those in the remaining groups. Conclusions Danhong injection may improve the microenvironment of stem cell transplantation, enhance the survival rate of transplant NSC and improve the therapeutic effect of NSC transplantation for cerebral ischemia injury probably by regulating the Nrf2 signaling pathway.

To establish a simple, quick and effective method to get a large amount of spider toxin JZTX-26 (35 aa) and JZTX-51 (27 aa) with 3 disulfide bonds each, the mature peptides coding gene fragments were constructed and fused with maltose-binding protein (MBP) tag in an Escherichia coli expression vector pMAL-p2x. The recombinant constructs pMAL-jz26 and pMAL-jz51 were transformed and cultured in E. coli TB1 and BL21 (DE3). After being induced by isopropyl-β-d-thiogalactoside (IPTG), the periplasmic proteins were purified by amylose affinity chromatography and analyzed by SDS-PAGE. The fusion proteins were digested with factor X, and purified by Sizes-Exclusion chromatography and Reversed Phase HPLC. Molecular weights of the purified peptides were obtained by using a MALDI-TOF-TOF mass spectrometer, which were consistent with the theoretical molecular weights. Five milligram of target protein could be purified from 1 L of culture medium. The results indicate that the peptides with three disulfide bonds can be expressed by using the prokaryotic expression system with MBP tag. Our findings suggest the possibility of genetic engineering to obtain large amount of spider peptide toxins.

Objective To analyze the features of health economics in the treatment of leukemia;To evaluate the improvement trend of levels of clinical diagnosis, treatment and management. Methods TCM medical information dtatabase and electronic medical system in Zhejing Province TCM Hospital from January 2010 to December 2015 were retrived. According to inclusion and exclusion criteria, leukemia patients’ materials that met the critiria were screened. The total hospitalization fees, cost of Western medicine, the cost of Chinese patent medicine, cost of TCM decoction pieces, and cost of blood transfusion were set as costs, while white blood cell count, hemoglobin concentration, and platelet count were set as effectiveness indicators for cost effectiveness analysis. Results In patients with low white blood cell count increased unit white blood cell count, patients with high white blood cell count declined unit white blood cell count, patients with low hemoglobin increased unit hemoglobin count and patients with low platelet count increased unit platelet count, the total hospitalization fees, cost of Western medicine, the cost of Chinese patent medicine, cost of TCM decoction pieces, and blood transfusionfor the above increases showed a decreasing trend. Conclusion Health economics advantages in three blood routine indicators after treatment of integrated traditional Chinese and western medicine for leukemia is increasing year by year.

Background Choroidal neovascularization (CNV) leads to blindness in many fundus diseases.Study showed that naringenin suppresses CNV,but it presents with poor bioavailability because of its poor solubility in water.β-cyclodextrin (β-CD) can increase the water-solubility of drugs, however, whether the inhibitory effect of naringenin on CNV can be improved after clathrated with β-CD remains unclear.Objective This study was to compare the inhibitory effects of naringenin with naringenin/β-CD compounds on CNV in rats.Methods Naringenin/β-CD clathrate compounds were prepared with saturated solution,the solubility of naringenin in water was calculated based on standard curve.Thirty-two male Brown Norway rats were randomized into normal control group, model control group, naringenin group and naringenin/β-CD group.Laser-induced CNV models were created in the right eyes of rats from the model control group, naringenin group and naringenin/β-CD group.Naringenin and naringenin/β-CD clathrate compounds were intraperitoneally injected at a dose of 20 mg/kg in the rats of naringenin group and naringenin/β-CD group since the day after modeling, respectively, once per day for 4 weeks, and equal volume of DMSO was injected in the same way in the model control group.Fluorescein isothiocyanate dextran (FITC-D) was injected via rat hypoglossal vein for the preparation of flatmounts of choroid in the fourth week,and the areas of CNV were measured and compared among the groups.The retinal pigment epithelium (RPE)-choroid-sclera tissues were isolated from the rats, and the relative expression levels of vascular endothelial growth factor (VEGF) , cyclooxygenase-2 (COX-2),phosphatidylinositol-3-kinase (PI3K),p38mitogen-activated protein kinase (p38MAPK), matrix metalloproteinase (MMP)-2, MMP-9 mRNA and their proteins in RPE-choroid-sclera tissue were detected using real-time PCR and Western blot.Results The solubility of naringenin in water increased by 11.8 folds after encapsulated with β-CD.The CNV areas in the model control group, naringenin group and naringenin/β-CD group were (34.56± 1.67), (20.90± 1.47) and (13.20± 1.38) × 103 μm2 , respectively, showing significant reduces in the naringenin group and naringenin/β-CD group compared with the model control group (t =3.973 ,P＜O.05;t =5.532, P＜0.01) ,and the CNV area in the naringenin/β-CD group was significantly smaller than that in the naringenin group (t =3.605,P＜0.05).The relative expression levels of VEGF, COX-2, PI3K, p38MAPK, MMP-2, MMP-9 mRNA and their proteins were significantly declined in the normal control group,naringenin group and naringenin/β-CD group in comparison with the model control group (all at P＜0.05).In addition, the expression levels of VEGF mRNA and COX-2 mRNA and their proteins were significantly lower in the naringenin/β-CD group than those in the naringenin group (all at P＜0.05).Conclusions The naringenin/β-CD clathrate compounds can improve the water solubility of naringenin and enhance their inhibitory effect on rats CNV.The inhibitory effect of naringenin on rats CNV probably is associated with anti-inflammatory pathway.

ObjectiveTo investigate the application value of digital three-dimensional reconstruction in liver transplantation for hepatic alveolar echinocoecosis (HAE).MethodsClinical data of 21 patients with end-stage HAE undergoing liver transplantation (LT) and 6 living donors in the First Affiliated Hospital of Xinjiang Medical University between April 2012 and December 2014 were retrospectively studied. Among the 21 patients, 13 were males and 8 were females with the average age of (43±13) years old. Among the 6 donors, 4 were males and 2 were females with the average age of (40±9) years old. Fifteen cases underwent extracorporeal hepatectomy and autotransplantation and 6 cases underwent living donor LT. The informed consents of all patients and 6 living donors were obtained and the local ethical committee approval had been received. All patients and donors received computer tomography (CT) plain scan, 3-phase (arterial phase, portal venous phase and delayed phase) enhancement scan and computed tomography angiography (CTA). The total liver volume and the liver graft volume were measured according to the two-dimensional liver image. The digital three-dimensional liver reconstruction software was used to perform three-dimensional model reconstruction. The total liver volume and the liver graft volume were measured a second time. The liver section was designed and the individualized virtual surgery was performed. The actual total liver volume and the liver graft volume were measured during LT to assess the error rate of liver volume predicted before operation. The comparison of liver volume data was conducted usingt test and the comparison of the error rate of liver graft volume was conducted using Chi-square test.Results The intrahepatic anatomical relationship was clearly displayed by the three-dimensional model, which was in accordance with that observed during operation. The liver graft volume of 15 patients undergoing extracorporeal hepatectomy and autotransplantation and 6 patients undergoing living donor LT calculated by the digital three-dimensional reconstruction technology was (766±197) ml, which was signiifcantly smaller than (833±243) ml calculated by the two-dimensional measurement (t=-3.674,P<0.05). Compared with the actual liver graft volume of (955±194) ml measured during operation, the average error rate of the liver graft volume calculated by the three-dimensional reconstruction technology was (6±1) %, which was signiifcantly smaller than (13±2) % of that calculated by two-dimensional measurement (t=-14.346,P<0.05). The liver graft volume measured by the three-dimensional measurement was positively correlated with the actual liver graft volume measured during operation (r=0.967,P<0.05). All the operations were completed successfully. One patient died of acute renal failure 12 d after LT. No case was observed developing liver failure or hemorrhage or other severe complications. The growth of the liver graft was good and the anastomotic stoma of intrahepatic vessels was clear by CT reexamination and three-dimensional reconstruction after operation. ConclusionThe application of three-dimensional reconstruction technology in preoperative assessment and operation planning of LT for end-stage HAE can improve the precision and success rate and achieve good curative effect.

Objectiye To investigate the value of liver transplantation for the treatment of end-stage hepatic alveolar echinococcosis(HAE).Methods The clinical data of 8 patients with end-stage HAE who received liver transplantation at the First Affiliated Hospital of Xinjiang Medical University from December 2000 to August 2010 were retrospectively analyzed.The operation time,anhepatic phase,infusion of suspension of red blood cells and postoperative complications were observed.Results The median operation time,anhepatic phase and infusion of suspension of red blood cells were 635 minutes(range,490-760 minutes),66 minutes(range,44-240 minutes)and 20 U(range,4-40 U).Liver transplantation was successfully carried out on 7 patients except for 1 patient who received emergent liver transplantation died of severe hepatic encephalopathy,renal failure and coagulation disorder on postoperative day 1.The median follow-up time was 6 months(range,3-29 months).One patient died of septicopyemia in postoperative month 3,1 died of incurable infection of bile duct in postoperative month 5,and 1 died of acute rejection in postoperative month 6.One patient was complicated with stricture of the bile duct anastomosis,and was cured by choledochojejunostomy.The size of the metastatic lesion in the left lung of 1 patient was reduced.One patient who underwent liver autotransplantation had no signs of residual liver disease with good liver function.Conclusion End-stage HAE is an indication for liver transplantation.A minimum dose of immunosuppressive agent and systemic administration of anti-HAE drugs are necessary to prevent the recurrence of HAE and ensure a long-term survival.Liver autotransplantation is the optimal method for the treatment of end-stage HAE,because no immunosuppressive agent is needed after operation.