Objective To observe the effect of bortezomib on acute graft-versus-host disease (aGVHD) in an aGVHD model of mice and investigate the related mechanism. Methods Male C57BL/6( H-2Kb)mice were used as donors and female Balb/c (H-2Kd) mice used as recipients. Balb/c mice received total body irradiation (TBI) by 7.0 Gy X-radiation, and randomly divided into five groups. normal (group A), TBI (group B), TBI + bortezomib (group C), TBI + bone marrow cells (BMC) + spleen cells (SC) (group D) and TBI + bortezomib + BMC + SC (group E). The physical signs and the pathological damage of aGVHD, mean survival time, and chimerism were observed in recipients. The NF-κB p65 levels in nuclei of the liver and small intestine tissues of groups A,B and C were analyzed by Western blot. Results ( 1 ) The clinical aGVHD score in group D was (7.37±0. 32), significantly higher than in group E (5.85 ± 0.40) (P＜0. 05). Histopathology of the gut, liver and skin illuminated that the Ⅲ-Ⅳ degree GVHD occurred in group D. The occurrence of aGVHD in group E was later than in group D. The symptoms and the pathological damage of aGVHD in group E were milder than in group D. The average survival time in group E was significantly longer than that in group D (P＜0.05). The percentage of donor-derived cells in recipient mice was above 90% at day 12 after transplantation; (2) NF-κB p65 levels in nuclei of the liver and small intestine tissues in group B was significantly higher than in group C on the day 1,3 and 5 (P＜0. 05). Conclusion Bortezomib can inhibit the activation and expression of NF-κB,which may be the underlying mechanism for it to relieve aGVHD.

Objective To investigate the clinical features of young female patients with acute myocardial infarction (AMI) who were referred to Peking Union Medical College Hospital. Methods A total of 24 consecutive AMI female patients (age≤44 years) who underwent coronary angiography were retrospectively retrieved from the database, and 70 AMI patients whose age ≥ 65 years and who also underwent coronary angiography were enrolled as a control (elderly) group. Clinical features were compared between the two groups. Results Of the 24 young female AMI patients, MI from non-atherosclerosis was identiifed in 9 patients (non-ATS group). Compared to the remaining 15 young female AMI patients (ATS-group), non-ATS group was younger (P<0.05), with lower BMI (P<0.05) and less traditional risk factors of coronary heart disease (P<0.05). Coronary angiography showed more normal artery (P<0.05) and lesions on left main (P<0.05). However, when compared to the elderly group, the young female ATS-group was associated with less hypertension (P<0.01), smoking (P<0.05), traditional risk factors (P<0.01) and lower level of blood pressure (P<0.05), fasting glucose (P<0.05), serum creatine (P<0.01), TC (P<0.05), and LDL-C (P<0.01) at admission. Coronary angiography showed single vessel disease was the most common lesion. Conclusions Acute myocardial infarction in young female might be caused by non-atherosclerosis. Those due to atherosclerosis differ in coronary risk factors and angiographic features from the elderly female AMI patients.

Objective To explore the influence of the lentiviral vectors-mediated mouse genetic engineering regulatory T cells (Treg) infused after allogeneie bone marrow transplantation (allo-BMT)on graft-versus-host disease (GVHD) in mice.Methods Lentivirus-mediated expression of Forkhead box P3 (Foxp3) converted CD4~+ CD25~- T cells from Balb/c mice into engineered Tregs in vitro.An allo-BMT model of Balb/c→C57BL/6 mice was established.Mice were randomly assigned into four groups:(1) The recipients in engineering Treg group were injected with 5×10~6 donor bone marrow cells and 5×10~6 splenoeytes plus 5×10~6 genetic engineering Treg;(2)The recipients in transplantation control group were iniected with 5×10~6 donor bone marrow cells and 5×10~6 splenocytes;(3) The recipients in radiation group were injected with 0.2 ml RPMI 1640;(4)The recipients in empty vector control group were injected with 5×10~6 donor bone marrow cells and 5×10~6 splenocytas plus 5×10~6 empty vector transduced CD4~+ CD25~- T cells.Survival time,clinical GVHD Score or histopathological analysis(skin,liver and small intestine) were observed after allo-BMT.Chimerism of bone marrow cells from recipients survived for 60 days after transplantation was measured Results The mean survival times in radiation group, transplantation control group,erIgineering Treg group and empty vector control group were (8.8±0.6),(36.7±2.5),(51.6±4.0) and (34.1±2.3)days respectively.The survival time in engineering Treg group was signiticantly prolonged as compared with other groups as judged by the log-rank test(P<0.05).Histopathological ahalysis in several target organs (skin,liver and small intestine)confirmed the presence of severe GVHD in transplantation control group and empty vector control group. No histological signs of GVHD were observed in recipients in engineering Treg group and clinical GVHD scores in this group were significantly decreased compared to transplantation control group and empty vector control group. Conclusion Co-injection of genetic engineering Treg can efficiently prevent recipients from lethal GVHD during allo-BMT in mice

Objective To explore the influence of the lentiviral vectors mediated mouse genetic engineering regulatory T cells(Tr) infused after allogeneic bone marrow transplantation(allo-BMT) on graft-versushost disease(GVHD) in mice. Methods Lentivirus-mediated expression of forkhead box P3 (Foxp3) converted CD4 + CD25 - T cells from BALB/c mice into engineered Tr in vitro. An allo-BMT model of BALB/c→C57BL/6 mice was established. After irradiation, the recipients were injected with donor cells along with genetic engineering Tr. Survival time, histopathological analysis, serum levels of inflammatory cytokines were observed after allo-BMT. Results The mean survival times in radiation group, transplantation control group, engineering Tr group and empty vector control group were ( 8.8 ± 0.6 ) d, ( 36.7 ± 2.5 ) d, ( 51.6 ± 4.0 ) d and ( 34.1 ± 2. 3 ) d. The survival time in engineering Tr group was significantly increased as compared to other groups as judged by the log-rank test ( P ＜0.05 ). Histopathological analysis in several target organs( skin, liver and small intestine) confirmed the presence of severe GVHD in transplantation control group and empty vector control group. No histological signs of GVHD were observed in recipients in engineering Tr group. The serum levels of IFN-γ, IL-2 and TNF-α were all increased after transplantation in above groups. The peaks of concentrations of IFN-γ, IL-2 and TNF-α in engineering Tr group were significantly decreased compared to transplantation control group and empty vector control group at day 21 ( P ＜ 0. 05 ). Conclusion Co-injection of genetic engineering Tr can efficiently prevent recipients from lethal GVHD during allo-BMT in mice by reducing the serum levels of inflammatory cytokines.

Objective To explore the influence of the lentiviral vectors-mediated mouse genetic engineering regulatory T cells (Treg) infused after allogeneic bone marrow transplantation (alloBMT) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect in mice.Methods Lentivirus-mediated expression of Forkhead box P3 (Foxp3) transformed CD4 + CD25- T cells from Balb/c mice into engineered Tregs in vitro. An allo-BMT model of Balb/c→C57BL/6 mice was established. The recipients were given lethal X-ray total body irradiation before transplantation.Mice were randomly assigned into five groups and each group contained 10 recipients: (1) The recipients in radiation group were injected with 0.2 ml RPMI 1640; (2) The recipients in leukemia control group were injected with 5 × 106 donor bone marrow cells and 500 mouse T-cell leukemia/lymphoma cells (EL4 cells); (3) The recipients in transplantation control group were injected with 5 × 106 donor bone marrow cells and 5 × 106 splenocytes plus 500 EL4 cells; (4) The recipients in engineering Treg group were injected with 5 × 106 donor bone marrow cells, 5 × 106 splenocytes and 500 EL4 cells plus 5 × 106 genetic engineering Treg; (5) The recipients in empty vector control group were injected with 5 × 106 donor bone marrow cells, 5 × 106 splenocytes and 500 EL4 cells plus 5 × 106 empty vector-transduced CD4+ CD25- T cells. Survival time, clinical GVHD score or histopathological analysis (skin, liver and small intestine) were observed after allo-BMT. Chimerism of bone marrow cells from recipients survived for 60 days after transplantation was measured. Results The mean survival time in radiation group, leukemia control group, transplantation control group,engineering Treg group and empty vector control group was ( 10. 3 ± 1.5), (20. 7 ± 1.9), (26. 0 ±4.3), (49. 0 ± 17. 7) and (24. 4 ± 4. 1 ) days respectively. The survival time in engineering Treg group was significantly prolonged as compared with other groups as judged by the log-rank test (P＜0. 05).Histopathological analysis in several target organs (skin, liver and small intestine) confirmed the presence of severe GVHD in transplantation control group and empty vector control group. No histological signs of GVHD or leukemia were observed in recipients in engineering Treg group and clinical GVHD scores in this group were significantly decreased as compared with transplantation control group and empty vector control group. Conclusion Co-injection of genetic engineering Treg can efficiently prevent recipients from lethal GVHD without affecting GVL activity during allo-BMT in mice.

Objective To explore the different expression of NF-κB in both K562 and its multidrug resistant cell line K562/A02 and discuss the mechanism of muhidrug resistance(MDR). Methods To detect the growing feature of the cells. Flow cytometry was used to analys the difference between the distribution profile of K562/S and K562/A02 cell. MTT colorimetry was used to determine the cytotoxic effect of adramycin, and expression of mdrl gene was detected by semi-quantitative reverse transcriptase poly-merase chain reaction (RT-PCR) in K562 and K562/A02 cells. FACS was used to determine the expression and function of glycoprotein (P-gp) on the cell membrane. Western blotting was used to determine the NF-κB p65protein in nueleus. Results There was a difference between K562 and K562/A02 cells growed in a halfadherent way rather than suspending ones, there were increases in the percentage number of cells at G0/G1 and S phases(P ＜0.05). This was mirrored by a decreasing number of cells within the G2/M phase(P＜0.05). Butthere was no difference in apoptosis rate(P ＞0.05). mdr1 mRNA was detected in K562/A02 cells, in which the expression P-gp was much higher [(94.17±0.89)%:(1.41 ±O.491)%]. NF-κB p65 protein in nucleus was overexpressed in K562/A02 cells. Conclusion The activation of NF-κB signaling pathway may attribute to the formation of MDR in K562/A02 cells.

Growth year is one of the important factors for the quality of Polygala tenufolia. In this study, primary metabolites and secondary metabolites were compared in 1, 2 and 3 years old P. tenufolia cultivated in Shaanxi Heyang. The samples were subjected to ultra-high performance liquid chromatography (UPLC)-quadrupole time-of-flight mass spectrometry (Q-TOF MS) and nuclear magnetic resonance (NMR) analysis, and the obtained data were analyzed using principal component analysis (PCA) and other statistical analysis methods. In addition, content and correlation of different metabolites were also calculated. The results showed no significance between main component contents in 2 year-old and 3 year-old P. Tenufolia, but 1 year-old was statistically different. The contents of primary metabolites, such as fructose, sucrose, and choline increased as time goes on, while glycine and raffinose decreased. The contents of secondary metabolites, such as onjisaponin Fg, polygalasaponin XXVIII, polygalasaponin XXXII increased, while polygalaxanthone III and parts of oligosaccharide multi-ester including tenuifoliose A, tenuifoliose C, tenuifoliose C2 and tenuifoliose H decreased with the extension of the growth years. Growth years has important impact on the quality of P. tenuifolia and the existing growing years of commodity P. tenuifolia have its scientific evidence. This study supplied a new method for the quality evaluation of Chinese medicinal materials.

OBJECTIVE:To investigate the application effect of PDCA circulation method in clinical pharmaceutical care. METHODS:According to the method of PDCA cycle,clinical pharmaceutical care quality and satisfaction degree of physicians, nurses and patients in 2013 were investigated to find out the problems;the reasons were analyzed and countermeasures were made out,checked and implemented. Finally,the quality of clinical pharmaceutical care,the medical staff and patient's satisfaction with clinical pharmaceutical care were compared before and after the implementation of PDCA circulation. RESULTS:Due to the poor quality of clinical pharmaceutical care and low satisfactory degree of our hospital,we formulated related countermeasures,such as enhancing the medication service skill of clinical pharmacists in obstetrics and gynecology department,extending the coverage of pharmaceutical ward round,developing the pharmaceutical care for patients with high risk pregnancy or underwent assisted repro-duction,strengthening communication and propaganda of medical staff and patients. After the implementation of countermeasures, the quality indicators of clinical pharmaceutical care were improved in 2014,compared to 2013,such as the number of patients in-cluded in pharmaceutical ward round increased from 445 to 1 780;total number of reasonable medication intervention suggestion in-creased from 14 to 29;that of pharmaceutical consultation increased from 8 to 23;the satisfaction degree of medical staff and pa-tients improved from 55.93% and 45.95% to 100% and 92.10%,respectively. CONCLUSIONS:PDCA circulation can significant-ly improve the quality of clinical pharmaceutical care and satisfactory degree of our hospital,and promote pharmaceutical care of our hospital.

Objective To establish standard parameters of cervical alignment and cervical range of motion(ROM) in asymptomatic population,and to explore the influential factors such as age,sex and cervical disc degeneration.Methods The cervical standard lateral,flexion and extension plain radiographs of 212 asymptomatic volunteers were analyzed retrospectively.The volunteers,including 128 females and 84 males with ages ranging from 20 to 79 years,were divided into 6 groups from 3rd to 8th decade of life and were divided into 4 groups based on the scoring system of cervical disc degeneration.These plain films were blindly measured by 3 spine surgeons with Mimics software,and each spine surgeon mcasured them for 3 times.Several parameters,including C2-C7 cervical alignment,total ROM,flexion ROM,extension ROM and segmental ROM were measured.The score of disc degeneration were assessed from C2-C3 to C6-C7.Pearson correlation analyses was used to quantify the relation between cervical alignment and total ROM.Multiple linear regression analyses were required to account for influential factors.Inter-and intrarater correlation coefficient was analyzed.Results The C2-C7 cervical alignment was 21.40°± 12.15°,and the total ROM was 63.59°± 15.37°.Sex had a significant impact on the cervical alignment (regression coefficient was-2.472,P ＜ 0.05).Both sex and age had significant impacts on the total ROM (regression coefficient was 3.863 and-6.463 respectively,P ＜ 0.05).Sex had a significant impact on C2,3 and C5,6 segmental ROM; age had a significant impact on all of the five segmental ROM from C2,3 to C6,7; cervical disc degeneration had a significant impact on the C4-5,C5-6 and C6-7 segmental ROM.The cervical alignment had no significant association with both of the extension and total ROM (r=-0.106 and 0.215,respectively,P ＞ 0.05),but had a significantly negative association with flexion angle (r=-0.401,P＜ 0.05).The measurement of cervical alignment,total ROM and segmental ROM showed excellent intra-rater agreement and excellent inter-rater agreement.Conclusion Sex is an influential factor of the cervical alignment.Sex and age are two influential factors of the total ROM.Sex,age and cervical disc degeneration are influential factors of the segmental ROM.The cervical alignments do not have an impact on total ROM.

Objective To assess the functional role of TH 17 cells in allogeneic hematopoietic stem cell transplantation (allyHSCT).Methods Bone marrow monocytes and splenic T cells were enriched from C57/BL6 donors.Recipient Balb/c mice were irradiated with 7.5 Gy total body irradiation (TBI) and injected with 5 105 splenic T cells and 5 106 bone marrow monocytes.Survival was monitored daily,clinical graft-versus-host disease (GVHD) was assayed three times a week,and detailed histopathologic analyses of lung were performed at day six after Allo-HSCT.Flow cytometry analysis was performed using CD3-FITC,CD4-PE,CD45-PerCP-CyS.5 monoclonal antibodies.Cells were stained for intracellular cytokines using mouse TH 1/TH2/TH 17 cytokine kit.Results All the experimental animals showed GVHD manifestations on the day 6 after transplantation.Animals from BMT and HF groups were scarified and histological analysis of lung was performed.Absence of TH 17 cells induced severe pathologic pulmonary lesions.The histopathology of the lung tissue was characterized by disorganization,epithelia cell damage,interstitial fibroplasias,and monocytes infiltration.The proportion of TH1 and TH 17 in BMT group was (5.53 ± 0.11 ) ％ and ( 1.04 ± 0.34)％ respectively,both significantly different from that in HF group.The levels of IL-17A and IFN-γin BMT group were (2.81 ±0.19) and (42.97 ± 0.23) pg/mL respectively.IL-17A could not be detected in HF group,yet the level of IFN-y was only (9.89 ± 0.51 ) pg/mL.IL-10 in both HF and BMT groups was not detectable.Conclusion Lung is on target of aGVHD.IL-17A may play a key role in the lung injury after transplantation.