BACKGROUND: At present, the transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) or bone marrow-derived hepatocyte stem cells (BDHSCs) is common in the treatment of liver fibrosis, but the combined treatment for liver fibrosis is rarely reported. Combined transplantation of BM-EPCs possessing the function of angiogenesis and BDHSCs possessing the function of hepatocyte regeneration might play a dual anti-fibrosis role. OBJECTIVE: To evaluate the reversal effect on liver fibrosis by the combined transplantation of BM-EPCs and BDHSCs in rats. METHODS: The liver fibrosis rat models were induced with CCl4 subcutaneous injections for 6 weeks. BM-EPCs of rats with liver fibrosis were obtained by culture induction in vitro.BDHSCs of rats with liver fibrosis were obtained by magnetic bead cell sorting.BM-EPCs and/or BDHSCs were transplanted into liver fibrosis rats via the tail vein and branch of the portal vein,and then the effects of BDHSCs transplantatiron on liver fibrosis and liver function were observed. RESULTS AND CONCLUSION: (1) Masson staining results showed transplantations of BDHSCs and BM-EPCs, alone or both, could suppress the formation of collagen fibers. However, the staging scores of liver fibrosis showed that only the combined transplantation of BM-EPCs and BDHSCs could significantly improve liver fibrosis,which was significantly different from the model group(1.75±0.25 vs. 3.00±0.19, P < 0.05). (2) The liver biochemical assay in the blood showed that the levels of all five parameters of alanine aminotransferase, aspartate aminotransferase, total bilirubin, prothrombin time, and activated partial thromboplastin time in the BM-EPCs/BDHSCs group were significantly improved to be equivalent to normal levels, compared with those in the model group (P < 0.05). To conclude, it is an effective treatment for liver fibrosis by the co-transplantation of BM-EPCs and BDHSCs.

OBJECTIVETo study the effect of Xinnao Shutong capsule (XNST) on energy metabolism dysfunction, free radical injury and inflammatic factors in the course of acute cerebral ischemic damage, and try to reveal the mechanism of the protection against ischemia.

METHOD60 male Wistar rats weighing 280 - 320 g were randomly divided into five groups: normal, sham operation, model, XNST treatment( XNST-T) , and Western medicine treatment (WM-T) group. Acute multi-infarct model in rats was induced by injecting the embolus of blood powder through the right external carotid artery (ECA) into the internal carotid artery (ICA). At 72 hours after ischemia, morphologic change and the express of tumor necrosis factor-alpha (TNF-alpha) and interleukin -1beta ( IL-1beta) in hippocampus CAl section and cortex were observed, biochemical criterions including the activity of Na+ -K+ -ATPase, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in hippocampus were examined.

RESULTThe morphologic change of hippocampus and cortex in both XNST-T and WM-T groups was milder than that in model group. The activity of Na+ -K+ -ATPase, LDH and SOD in hippocampus were all significantly decreased in model group (P <0. 01), and elevated in XNST group (P <0. 01) as well as in WM-T group (P <0. 01). The content of MDA in hippocampus was significantly increased in model group (P <0. 05), and was reduced in XNST group (P <0. 05) as well as in WM-T group (P <0. 01).

CONCLUSIONThe results reveal that XNST has the protective effect against cerebral ischemic injury. And its possible mechanism is that XNST can prevent the upper pathological process.

Animals ; Brain Infarction ; complications ; Brain Ischemia ; etiology ; metabolism ; prevention & control ; Capsules ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Hippocampus ; drug effects ; metabolism ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Saponins ; isolation & purification ; pharmacology ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism ; Tribulus ; chemistry

Objective To study the effect of intestinal flora on the pharmacokinetics of ticagrelor in rats.Methods A total of 45 SD rats were randomly divided into control group,test A group and test B group.Rats of test groups were orally given live combined bifidobacterium and lactobacillus tablets for 7 days,respectively;rats of control group were given the same volume distilled water.On day 8,ticagrelor was orally administered to all rats.Blood samples were obtained at 0.08,0.25,0.50,1,1.5,2,3,4,6,8,12,24 h after ticagrelor administration.The plasma concentration of ticagrelor was determined by LC-MS/MS.The pharmacokinetic parameters were determined by DAS 2.1.1 software and the statistic analysis was processed with SPSS 21.0 software.Results The pharmacokinetic parameters of ticagrelor in the test A group,test B group and control group were as follows:AUC0-t were (6336.24 ± 1840.46),(4444.05± 1033.43) and (4469.32 ±928.47) ng· mL-1 · h-1;AUC0-∞ were (6841.98 ± 1975.95),(4656.66 ± 1083.78) and (4736.47 ± 897.42) ng · mL-1 · h;Cmax were (858.65 ± 275.98),648.81 ± 215.59) and (617.49 ± 168.95)ng · mL-1;t1/2 were (6.40 ± 2.18),(5.25 ± 1.39) and (5.68 ± 2.08) h;tmax were (0.88 ± 0.23),(0.90 ± 0.21) and (1.30 ± 0.59) h;clearance (CL) were (2.82±0.72) (4.07±0.99) and (3.95±0.91) L·h-1 ·kg-1;apparent volume of distribution (Ⅴ) were (26.07 ± 12.00),(31.45 ± 14.65) and (32.95 ± 14.17) L · kg-1.There were significant differences in AUC0-t,AUC0-∞,Cmax,tmax and CL between test A group and control group (P ＜ 0.05).On the contrary,no significant differences were observed on the pharmacokinetic parameters between test B group and control group.Conclusion Increased intestinal probiotics can increase the AUC0-t,AUC0-∞,and Cmax of ticagrelor,while decrease the CL of ticagrelor.

Objective The aim of this research is to identify and compare the adjustment levels in patients with temporary and permanent colostomy, and to provide evidence to improve nursing performance. Methods In the First, Second, and Third Affiliated Hospital of Kunming Medical University, 52 patients with colorectal stoma participated in the research and completed the questionnaire of OAS (Ostomy Adjustment Scale) and demographic data. The data were established using Epidata 3.1, then analyzed with SPSS 17.0. The results were described using frequency, mean, stand deviations, and p values.Results Patients with permanent colostomy gained higher scores in OAS scores and psychological adaptation. Patients with temporary colostomy had higher scores in physical adaptation and social adaptation. Conclusion The nursing staff will promote the quality of life for this population from multiple perspectives in the future.

Objective To discuss the factors influencing the concentrations of clopidogrel active metabolite in plasma of patients with acute coronary syndrome(ACS).Methods One hundred and five patients with ACS were administrated aspirin (100 mg · d-1) and clopidogrel (75 mg · d-1) for 4 days.On day 5,blood samples (approximate 4 mL) were collected at 1 h after administration with empty stomach.Half of the blood added 20 μL 2-Bromo-3'-methoxyacetophenone (MPB,500 mmol · L-1) immediately was used for the determination of clopidogrel active metabolite.And the other was used for detecting the cytochrome P450 2C19 * 2 (CYP2C19 * 2),* 3,and paraoxonase-1 (PON1).By using single factor analysis,the binary variable and ranked data related to the blood drug concentration of clopidogrel active metabolites were analyzed.And the measurement data related to the blood drug concentration of clopidogrel active metabolites were analyzed using Spearman analysis.Results The concentration of clopidogrel active metabolites had a significantly negative correlation with diabetes,hyperlipidemia,percutaneous coronary intervention (PCI),PON1 carrier (P ＜ 0.05);but positive correlation with β-blockers,statins and serum albumin(ALB) (P ＜ 0.05).Conclusion The diabetes,hyperlipidemia,PCI can reduce the concentration of clopidogrel active metabolites in blood;while the ALB,β-blockers and statins can increase the concentration of clopidogrel active metabolites in blood.

Objective To study the prevention and foreseeing nursing of the complications of interventional therapy for carotid cavernous fistula (CCF). Methods The foreseeing nursing and reasons for the complications of interventional therapy for CCF were analyzed in the 16 patients. Results 16 patients were embolized successfully.Exophthalmos and vascular murmur were relieved. The most common complications were bleeding of the puncture,cerebral vasospasm, cerebral hemorrhage, cerebral embolism and hyperperfusion syndrome. 1 patient was reembolized for the rupture of balloon. Vascular vasospasm was relieved after treatment in 2 patients. Hyperperfusion syndrome was relieved after lower blood pressure in 1 patient. Conclusions Interventional embolization was an effective treatment for CCF. Foreseeing nursing was the key to ensure the treatment effect.

OBJECTIVETo observe the effect of vascular endothelial growth factor (VEGF) on bone marrow-derived mesenchymal stem cell (MSC) proliferation and explore the signaling mechanism involved.

METHODSMSC culture was performed following the classical whole bone marrow adhering method. The characteristics of MSC were identified by induction of multi-lineage differentiation and flow cytometry for surface marker analysis (CD34, CD45, CD29, and CD90). Following the addition of 50 nmol/L wortmannin, 50 µmol/L PD98059, 30 µmol/L SB203580, 10 µmol/L H89, 20 µmol/L Y27632, 1 µmol/L rapamycin, 10 µmol/L straurosporine, 6 nmol/L Go6976, or 50 µmol/L Pseudo Z inhibitors in the cell culture, the MSC were treated with 20 ng/ml VEGF and the changes of the cell proliferation rate was measured with MTT assay.

RESULTSCultured MSC were capable of multi-linage differentiation and did not express VEGF-R, CD29 or CD90. Treatment with 20 ng/ml VEGF obviously promoted MSC proliferation, and this effect was inhibited partially by p38 mitogen-activated protein kinase (MAPK) inhibitor rapamycin, PD98059, SB203580, Go6976, and straurosporine.

CONCLUSIONSVEGF promotes MSC proliferation in close relation to the AKT-PKC pathway, in which PKC signal pathway may play the central role.

Animals ; Bone Marrow Cells ; cytology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Female ; Male ; Mesenchymal Stromal Cells ; cytology ; Protein Kinase C ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vascular Endothelial Growth Factor A ; pharmacology

OBJECTIVETo explore the correlation between single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) gene and the susceptibility to primary hepatocellular carcinoma (HCC).

METHODSA total of 300 histologically confirmed HCC cases (from November 2001 to April 2010) and 310 healthy controls with no history of chronic hepatitis B or hepatocellular carcinoma (2009-2010) were selected from a hospital in Guilin and a hospital in Beijing for this case-control study.139 HCC patients in the case group had complete clinical tracking data. All the subjects were Han Chinese, with no age or gender restrictions.2 ml peripheral blood samples were drawn from each subject with informed consent. SNP of rs12972991, rs4803223, rs8099917 and rs12979860 four loci in IL-28B gene were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF).

RESULTSThe frequencies of C allele at rs12972991, G allele at rs8099917 and G allele at rs4803223 were 6.7% (40/598), 7.9% (47/598) and 10.0% (59/588) respectively in case group; all higher than the corresponding frequencies in control group, separately 2.9% (18/618), 4.1% (25/616) and 3.6% (21/608). The differences were statistically significant (χ2=9.542, 7.858, 20.736, P values all<0.05). The above alleles could increase the risk of HCC, and the OR (95%CI) values were separately 1.67 (1.13-2.46), 1.49 (1.08-2.06) and 2.91 (1.79-4.72). The genotype frequencies of AC+CC at rs12972991, GT+GG at rs8099917, GA+GG at rs4803223 were 13.0% (39/299), 14.7% (44/299) and 19.0% (56/296) respectively in case group; while the frequencies were lower in control group, separately 5.8% (18/309), 8.1% (25/308) and 6.6% (20/304). The differences were statistically significant (χ2=9.319, 6.557, 20.948, P values all<0.05). These genotypes may increase the risk of HCC, and the adjusted OR (95%CI) values were 2.24 (1.31-3.83), 1.81 (1.14-2.88) and 2.90 (1.78-4.70), respectively. The stratified analysis of the clinical data indicated that the frequency of genotype GA+GG at rs4803223 was 50.0% (13/26) in patients of tumor thrombosis in portal vein (TTPV), higher than the frequency of genotype AA (21.1%, 23/109). The difference was statistically significant (χ2=8.965, P=0.003).

CONCLUSIONThe results suggested that IL-28B gene polymorphisms was correlated to the susceptibility to HCC in Chinese Han ethnic population. Among them, GA + GG genotype at rs4803223 could increase the risk of TTPV in HCC patients.

Alleles ; Carcinoma, Hepatocellular ; genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukins ; genetics ; Liver Neoplasms ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

In this study, the thermoresponsive micelles were synthesized with random copolymerization method and the photosensitizer indocyanine green (ICG) was loaded on micelles through the physical adsorption. The light energy was converted into heat energy to increase the temperature after irradiation with near-infrared light. When the phase transition temperature was reached, the micelle was disassembled and the targeted therapy was achieved. The nanoparticles were characterized with a transmission electron microscopy, Fourier transform infrared spectrometer, nuclear magnetic resonance spectrometer and other characterization were used to investigate. The critical micelle concentration (CMC), upper critical solution temperature, the photothermal properties of the carrier and the release of drug triggered by light were investigated after the doxorubicin (DOX) loaded. The carrier was evaluated for toxicity, cellular uptake, the effect of photothermal, the combination of photothermal and chemotherapy; the p(AAm-co-AN)-g-PEG (PAAP) was spherical in shape with a particle size of about 45 nm and a phase transition temperature was about 43℃. The critical micelle concentration was 24 μg·mL^-1. The particle size increased to 88 nm after loaded with ICG and DOX which the photothermal effect was obvious. The cumulative release of the drug under the irradiation of near-infrared light (808 nm, 2 W·cm^-2, 2 min·h^-1) was increased to 59.4% (pH 5.0) after 5 h. The results of the cell experiment indicated that ICG-PAAP was almost non-toxic and uptaken by the lysosomal pathway. The cell killing effect was stronger with combination of chemotherapy (DOX as 20 μg·mL^-1) with more than 70% of the cells killed. The results showed that the prepared micelle with low toxicity was thermoresponsive and could be used in combined therapy of tumor under the irradiation of near-infrared light.

In this study we investigate the effects of cadmium stress on Astragalus membranaceus seedlings and the alleviative effects of attapulgite clay in growth substrate on cadmium stress to A. membranaceus seedlings. The results showed that the Y (Ⅱ) (effective photochemical quantum yield of PSⅡ photosynthetic), qP(photochemical quenching coefficient), ETR(the rate of non-cyclic electrontransport through PSⅡ), and chlorophyll content of the leaves were significantly decreased with the increase of cadmium concentrations, while the cadmium content, non-photochemical quenching(NPQ, qN) of the leaves and cadmium content, MDA content, plasma membrane permeability, and the damage degree of root apical membrane of the roots were significantly increased. Simultaneously, the activities of APX(ascorbate peroxidase), SOD(superoxide dismutase), POD(peroxidase), CAT(catalase), soluble protein content, and soluble sugar content of roots were increased first but then decreased with the increasing cadmium concentration. Under the condition of without Cd stress, the attapulgite clay into the growth substrate did not significantly affect above physiological indexes of leaves, but significantly increased SOD activity and soluble sugar content of roots and decreased the MDA content, damage degree of root apical membrane of roots, while other physiological indexes did not significantly change. Under cadmium stress, the presence of attapulgite clay in the growth substrate significantly alleviated the cadmium-induced decreases Y (Ⅱ), qP, ETR and chlorophyll content of leaves, and the CAT activity, soluble protein content, and soluble sugar content of roots. Under condition with cadmium stress, the presence of attapulgite clay significantly alleviated the cadmium-induced increases of leaves cadmium content, qN and NPQ, and the cadmium content, MDA content, plasma membrane permeability, damage degree of root apical membrane, SOD, POD, and APX activity of the roots. And, the alleviative effects of attapulgite clay on cadmium stress to A. membranaceus roots were more obvious with the increase of cadmium stress time. The above results showed that the addition of attapulgite clay into the growth substrate has certain alleviative effect on the cadmium stress to A. membranaceus seedlings.