OBJECTIVE:To study the pharmacodynamics of Compound xiangqi granules in vitiligo model guinea pigs. METH-ODS:The vitiligo guinea pigs model was established by chemical decolorization with hydrogen peroxide. Then guinea pigs were randomly divided into 5 groups after modeling,including model control group (water),vitiligo capsules group [positive control, 50 mg/(kg·d)] and Compound xiangqi granules low-dose,medium-dose and high-dose groups [25,100,and 400 mg/(kg·d)]. They were given related medicines intragastrically once a day for 40 days. The distribution of skin melanin and the number of black hair follicle were observed,and cholinesterase (ChE) activity,malondialdehyde (MDA) content of plasma and hemorheology in-dexes were detected. Blank control group had also been established. RESULTS:Compared with blank control group,the distribu-tion of skin melanin,the number of black hair follicle and ChE activity decreased in model control group,while plasma viscosity, whole blood viscosity and hematocrit increased significantly,and erythrocyte sedimentation rate decreased significantly;there was statistical significance(P<0.05 or P<0.01). Compared with model control group,except erythrocyte sedimentation rate and hema-tocrit of low-dose group,above indicators of positive control group and Compound xiangqi granules low-dose,medium-dose and high-dose groups were all improved;there was statistical significance(P<0.05 or P<0.01),showing good effectiveness-dose rela-tionship. CONCLUSIONS:Compound xiangqi granules improve relative indicators of experimental vitiligo model guinea pigs effec-tively.

Objective To investigate the relationship between the CD+4 CDHigh25 regulatory T cells and cytokine IL-10 and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Flow cytometric was used to detect the percentage of CD+4 CDHigh25Foxp3High Treg cell and CD+4 CDHigh25 CDLow127 Treg cell in CD+4 T cells and at the same time ELISA was used to test the serum IL-10 levels in corresponding period. Results 13 patients have received hematopoietic function reconstruction. aGVHD group of CD+4 CDHigh25 CDLow127/CD+4 and CD+4 CDHigh25 Foxp3High/CD+4 ratio were significantly lower than non-aGVHD group, the difference was statistically significant (P ＜0.01); Ⅲ-Ⅳ degree of aGVHD subgroup was lower than Ⅰ - Ⅱ degree of aGVHD subgroup, but no statistical significance(P ＞0.05); the same as between-group CD+4 CDHigh25 CDLow127/CD+4 and the CD+4 CDHigh25 Foxp3High/CD+4 has no significant difference;aGVHD group of IL-10 concentration was significantly lower than non-GVHD group, the difference was statistically significant (P ＜0.01). Treg cell and IL-10 changes in correlation, r = 0.557, P ＜0.05. Conclusion The level of Treg cell was closely related to the occurrence of aGVHD after allo-HSCT. So it is very important to monitor the Treg cell level for clinical early diagnosis of aGVHD and predict prognosis of aGVHD and guide the application of immunosuppressant. CD127 can serve as a Treg cell surface-specific marker, to promote the detection of Treg cell and purification. IL-10 was an important negative regulator. Treg cell and IL-10expression in patients with aGVHD was correlation, which may provide some basis for Treg cell immunosuppressive mechanism.

Objective To explore the effect of proteasome inhibitor bortezomib (BOR) on proliferation inhibition and apoptosis in imatinib-resistant chronic myeloid leukemia cell line K562/G01. Methods MTT assay was used to observe the effect of growth inhibitory of cells; flow cytometry was used to detect cell cycle and apoptosis. Results K562/G01 cells was not sensitive to imatinib,1C50 values of imatinib to K562 and K562/G01 cells was (20.09±1.38) and (0.54±0.13) μmol/L,respectively; BOR could inhibit proliferation in K562/G01 cell,peaked at 48 h,and IC50 value of BOR to K562/G01 was (23.10±2.71) nmol/L. G2/M phase cell cycle arrest and significant apoptosis peak could be seen by flow cytometry with increased in the concentration and action time of BOR. Conclusion BOR can inhibit proliferation and induce apoptosis in imatinib-resistant K562/G01 cell,the mechanism may be related to cell cycle G2/M phase arrest.

A novel chitosan derivant, N-octyl-N-arginine chitosan (OACS) with a mimetic structure of cell-penetrating peptides was synthesized by introducing hydrophilic arginine groups and hydrophobic octyl groups to the amino-group on chitosan's side chain. Structure of the obtained polymer was characterized by FT-IR and 1H NMR. The substitution degree of octyl and arginine groups was calculated through element analysis and spectrophotometric method, separately. The critical micelle concentration of OACS was 0.12 - 0.27 mgmL(-1) tested by fluorescence spectrometry. The solubility test showed OACS could easily dissolve in pH 1 - 12 solutions and self-assemble to form a micelle solution with light blue opalescence. The OACS micelles have a mean size of 158.4 - 224.6 nm, polydisperse index of 0.038 - 0.309 and a zeta potential of +19.16 - +30.80 mV determined by malvern zetasizer. AFM images confirmed free OACS micelle has a regular sphere form with a uniform particle size. MTT test confirmed that OACS was safe in 50 - 1 000 micromol-L(-1). The result of HepG2 cell experiment showed that the cell internalization of OACS micelles enhanced with increased substitution degree of arginine by 40 folds compared to chitosan. Thus, OACS micelles were a promising nano vehicle with permeation enhancement and drug carrier capability.

Objective To develop a simple, rapid and sensitive method for the determination of major compounds from Gardenia jasminoides Ellis using liquid chromatography tandem mass spectrometry (LC-MS/MS).Methods The analysis was performed on Dikma Diamonsil?C18 (100mm×4.6mm, 5μm) column with acetonitrile-0.1％acetic acid and 0.1％acetic acidwater as mobile phase at a rate of 0.4ml/min.The column temperature was set at 40℃and the injection volume was 2μl.Quantification of these compounds was performed by LC-MS/MS with positive or negative ion mode electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode.Nebulizer gas, 3L/h;drying gas, 15L/h;desolvation line (DL) temperature, 240℃;heat block temperature, 300℃;CID, 230kPa.The mass transition of the precursor/product ions was monitored at m/z 391.10→149.30for shanzhiside, 573.40→365.05for genipin-1-gentiobioside, 447.30→225.15for geniposide.Results The regress equation of shanzhiside, genipin-1-gentiobioside and geniposide were Y=243.810 X-289.957, r=0.999 9;Y=137.125 X+2 092.76, r=0.999 6;Y=2 030.32 X+823 213, r=0.999 8in the range of 10.76-215.2ng/ml;516-4 128ng/ml;2 000-20 000ng/ml respectively.This validated method has good repeatability, precision, recovery and stability.The results meet the requirements by regulation.Conclusion This method shortened the analysis time and improved efficiency.It assayed the three iridoid glycosides in Gardenia jasminoides Ellis sensitively and precisely.This method can be used for the quality control of Gardenia jasminoides Ellis.

Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Interferons ; therapeutic use ; Interleukin-2 ; therapeutic use ; Leukemia, Myeloid, Acute ; drug therapy ; Recurrence ; Remission Induction ; Thalidomide ; therapeutic use

Objective To analyze the clinical features,efficacy and outcomes in patients with transplantation associated thrombotic microangiopathy (TA-TMA).Methods The clinical data of 9 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed from January 2011 to August 2018 in Affiliated Tumor Hospital of Zhengzhou University.Results There were 6 male and 3 female patiens with a median age of 31 (12-38) years.The median time from transplantation to TA-TMA was 76 (24-155) days.The baseline blood and biochemical parameters at diagnosis of TA-TMA included median hemoglobin (Hb) 66 (58-77) g/L,platelet (PLT) count 22 (4-38) × 109/L,serum lactic dehydrogenase (LDH) 655 (305-4 238) U/L,blood urine nitrogen (BUN)level 15.9 (4.8-26.2) mmol/L,blood creatinine (Cr) level 118 (24-380) μmol/L.The proportion of median peripheral blood schistocytes was 2.6％(1.2％-9％).All patients had positive urinary occult blood tests,and urinary protein was seen in 4 patients.Three patients had mental symptoms.Coombs tests were all negative.The main treatments of TA-TMA composed of reduction and withdrawal of calcineurin inhibitor,steroids and plasma exchange.Response was seen in 4 patients.Patients who did not response to the treatment had a higher proportion of schistocytes,more severe acute graft-versus-host disease (aGVHD),more elevated serum LDH and other transplant-related complications.Conclusions TA-TMA after allo-HSCT is a serious complication with high mortality rate.The proportion of schistocytes in peripheral blood,serum LDH level and comorbidities are prognostic factors of clinical outcome.

Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.

Objective:To optimize the extraction process of the water extract of Zhenwutang and study on the preparation of gran -ule of Zhenwu decoction to provide reference for the development and utilization of Zhenwutang granule .Methods: Heating refluxing was used, and the effects of the ratio of solid to liquid , extraction time and times were investigated by orthogonal test .As the synthetic indices of evaluation , the yield of extraction and the contents of paeoniflorin and benzoylmesaconine measured by HPLC were deter -mined to confirm the optimal water extraction process of Zhenwutang granule .Besides, granularity pass rate, moisture, loss on drying, solubility and angle of repose of the granule were regarded as the indices to evaluate the best ratio of the excipients in the preparation of the granule by single factor test.Results:Paeoniflorin and benzoyl mesaconitine had good linearity within the range of 5.45-32.70μg (r=0.9996) and 3.24-16.80 μg(r=0.9997), respectively.The average recovery was 99.62％ (RSD =1.34％ , n=6) and 1017.2 ％(RSD=1.74％, n=6), respectively.The optimum extraction process was as follows :the ratio of solid to liquid was 1:12 with twice refluxing extraction ( 2h for each time) .The optimum granule forming process was as follows:the pharmaceutical excipients were a mixture of dextrin and soluble starch with the best ratio of 1:3. The granularity pass rate , moisture, loss on drying, solubility and angle of repose of the granule was94 .12％ ,4.87 ％, 0.93％,89 .23％ and 36.18°, respectively.Conclusion:The optimized re-fluxing extraction process is stable , reliable and feasible , and the prepared granule is in good formability and melting .

Penicillium decumbens T. is an important filamentous fungus for the production of cellulases to effectively degrade lignocellulose for second generation biofuel production. In order to enhance the capability of Penicillium decumbens to produce cellulases, we constructed a creB (a deubiquitinating enzyme encoding gene) deletion cassette, and generated a creB knockout strain with homologous double crossover recombination. This mutation resulted in a detectable decrease of carbon catabolite repression (CCR) effect. The filter paper activity, endoglucanase activity, xylanase activity and exoglucanase activity of the deltacreB strain increased by 1.8, 1.71, 2.06 and 2.04 fold, respectively, when comparing with the parent strain Ku-39. A 2.68 fold increase of extracellular protein concentration was also observed. These results suggest that the deletion of creB results in CCR derepression. These data also suggest that CREB influences cellulase production of Penicillium decumbens. In generation, this study provides information that can be helpful for constructing cellulase hyper-producing strain.
Cellulase ; biosynthesis ; Endopeptidases ; genetics ; metabolism ; Gene Knockout Techniques ; Lignin ; metabolism ; Mutant Proteins ; metabolism ; Penicillium ; enzymology ; genetics ; Recombination, Genetic ; Ubiquitinated Proteins ; genetics ; Ubiquitination