BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

AIM: To establish individualized drug therapy strategy for patients with rejection and hyperglycemia after liver transplantation. METHODS: Clinical pharmacist collaborated with the surgeons and participated in the diagnosis and treatment of rejection and hyperglycemia after liver transplantation. Taking together liver function, therapeutic drug monitoring, drug-drug interactions between tacrolimus and wuzhi capsule, individualized drug therapy was adapted to improve the prognosis. RESULTS: The patient recovered well and survived in good health till now. CONCLUSION: It is highly suggested that clinical pharmacists actively involved in treatment of more severe and difficult-to-treat disease and design the individualized dosing regimens. This will largely contribute in reduced adverse drug reaction, improved safety and effectiveness in drug use as well as the quality of life in the "post-transplantation era".

ObjectiveAlmond， which is bitter in taste， contains traces of toxic substances. For the sake of the safety of prescriptions containing this medicinal material， the processing method of "soaking in boiling water" was selected. Moreover， through literature research and network pharmacology， the characteristic index of this medicinal material was determined. On this basis， a method was established for the determination of amygdalin in Qingfei Paidu Granules （QFPD） and the transfer rate of it in the processing of this prescription was monitored， aiming at improving the quality control system of QFPD. MethodThe high performance liquid chromatography conditions are as follows： YMC Triart C₁₈ column （4.6 mm × 150 mm， 5 µm）， mobile phase of methanol-water with flow of 1.0 mL·min^-1， column temperature of 35 ℃， and detection wavelength of 210 nm. ResultThe linear curve fitted well and the average recovery of amygdalin was 97.74% with RSD of 4.3%. The transfer rates of amygdalin from the medicinal material to the extract， from extract to concentrate， and from concentrate to granules were investigated with this method. The result showed that the average transfer rate from the medicinal material to the granules was （60±3.91）%. The comparison of transfer rate between the processes suggesting that the extraction of the medicinal material might be the key part influencing the prescription preparation. ConclusionThe method is simple， sensitive， reproducible， stable， and accurate， and the index is reasonable. Thus， the method can be used for the quality control of QFPD and determination of transfer rate of components in the preparation of QFPD. This study further improves the quality control standard of almond in QFPD， which can serve as a reference for the clinical application of QFPD.

Objective:To explore the regulatory effect of glutathione S-transferase P1(GSTP1) on the radiosensitivity of mouse Lewis lung cancer (LLC) cells.Methods:GSTP1-shRNA lentivirus and negative control lentivirus were used to respectively infect the LLC cells, and stable transgenic strains were selected. Real-time PCR and Western blot were conducted to quantitatively measure the expression levels of GSTP1 mRNA and protein in the LLC cells to verify the knockdown effect. The cell counting kit-8(CCK-8) assay was used to detect cell viability after irradiation. The colony formation assay was utilized to assess the cell proliferation ability after irradiation. Flow cytometry was performed to assess the level of cell apoptosis after irradiation. The tumor-bearing mice were established and irradiated to detect the changes in the tumor volume after irradiation. TUNEL staining was employed to detect the level of tumor apoptosis after irradiation. Immunofluorescence was used to detect the number of CD 4+ CD 8+ T cells in the tumor after irradiation. Results:Real-time PCR and Western blot showed that after shRNA lentivirus interference, the expression levels of GSTP1 mRNA and protein were significantly down-regulated. Down-regulation of GSTP1 reduced cell viability and proliferation, and increased the rate of cell apoptosis after irradiation. The tumor volume of the tumor-bearing mice after irradiation in the GSTP1 knockdown group was significantly smaller than that in the NC group, whereas the tumor apoptosis rate was significantly higher and the number of infiltrating CD 4+ CD 8+ T cells in the tumor was remarkably higher compared with those in the control group. Conclusion:Knockdown of GSTP1 can significantly increase the radiosensitivity of LLC cells and enhance the infiltration of lymphocytes in tumor tissues.

Objective:To study the dose response of two-dimensional ionization chamber matrix detectors under IMRT fields irradiation at different gantry angles and different directions.Methods:After the dose calibration of the medical accelerator and the two-dimensional ionization chamber matrix detector respectively, the solid water phantom was used to cover the upper part of the two-dimensional ionization chamber matrix detector. Adjusting the thickness of the solid water, the effective distances between the effective measuring center of the two-dimensional ionization chamber matrix detector and the incident point of the central axis of the radiation on the surface of the phantom was always controlled at 5 cm. Four locations with 0、45、90 and 135 degrees of the long axis of the treatment bed were selected, and each location was irradiated by IMRT fields at different frame angle of 60°, 45°, 30°, 15°, 0°, -15°, -30°, -45° and -60°, respectively.Results:The dose deviation of the medical accelerator was less than 0.18% in the range of different rack angles. The directional response deviation of the two-dimensional ionization chamber matrix detector was less than 0.63%, and the measurement deviation of each probe of the two-dimensional ionization chamber matrix detector to its center probe was less than 0.50%.Conclusions:The two-dimensional ionization chamber matrix detector has good directional response and it is a useful tool for developing intensity-modulated radiotherapy technology. The method proposed in this study can provide a basic basis for the relevant medical accelerator metrology departments to formulate corresponding quality control test specifications.

Objective To investigate the change patterns of functional brain networks and their relations with cognitive function in patients with end-stage renal disease (ESRD).Methods Sixty-two patients with ESRD (ESRD group),admitted to our hospital from July 2018 to June 2019,and 36 age-,gender-,and education level-matched healthy controls (HC group) were enrolled.Mini-mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Trail Making Test A (TMT-A),TMT-B and Symbol Digit Modalities Test (SDMT) were used to evaluate the cognitive function for all subjects.Resting-state functional magnetic resonance imaging data were acquired;after data preprocessing,the brain functional networks were constructed and the topological parameters were calculated.Statistical methods were used to compare the differences of cognitive function scores and topological parameters between the two groups,and to analyze the correlations between these topological parameters and cognitive function scores in the ESRD group.Results The MMSE,MoCA and SDMT scores of the ESRD group were significantly lower than those of the HC group (P＜0.05),and the ESRD group took significantly longer time to complete TMT-A and TMT-B than the HC group (P＜0.05).The ESRD group had significantly lower normalized clustering coefficient (γ),small-worldness (σ) and local efficiency (Elocal) values than the HC group (P＜0.05).Patients in the ESRD group exhibited significantly decreased nodal efficiency in the paralimbic-limbic network (including the bilateral insula,median cingulate and paracingulate gyri,hippocampus,parahippocampal gyrus,amygdala,temporal pole:superior temporal gyrus,and temporal pole:middle temporal gyrus),right heschl gyrus and left superior temporal gyrus,and exhibited significantly increased nodal efficiency in the visual network (including the right distal-shaped gyrus,bilateral wedge,and left superior and middle occipital gyrus) as compared with the HC group (P＜0.05).In the ESRD group,the area under the curve (AUC) ofγ and σ was positively correlated with MoCA scores (r=0.698,P=0.000;r=0.661,P=0.000),and the AUC of Elocal showed positive correlation with MMSE scores (r=0.407,P=0.003).Conclusion Abnormal topological organization of the functional brain networks is revealed in patients with ESRD,which affects the cognitive function of these patients.

Objective To investigate the inter-hemispheric resting-state functional connectivity and its relation with cognitive function in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI) based on voxel-mirrored homotopic connectivity (VMHC). Methods A total of 52 patients with ESRD (ESRD group), admitted to our hospital from July 2018 to January 2019, were enrolled; 36 age-, gender-, and education level-matched healthy controls (HCs group) were collected at the same time period. The cognitive function of all subjects was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT)-A, TMT-B and Symbol Digit Modalities Test (SDMT). The rs-fMRI and 3D-T1WI data were acquired from all subjects; after image preprocessing, VMHC values between brain hemispheres were calculated and the regions with significantly different VMHC values were obtained. The correlations between VMHC values in significant regions and cognitive scale scores were analyzed. Results MMSE, MoCA and SDMT scores of ESRD patients were significantly lower than those of the HCs group (P<0.05), and ESRD patients took longer time to complete TMT-A and TMT-B tests than the HCs group (P<0.05). As compared with that of the HCs group, significant decrease of VMHC values of ESRD patients was found in the hippocampus, lingual gyrus, superior temporal gyrus, caudate nucleus and anterior cingulate gyrus (P<0.01, AlphaSim correction); the VMHC values of the anterior cingulate gyrus and hippocampus were positively correlated with MMSE and MoCA scores (P<0. 05). Conclusion Significant abnormal inter-hemisphere functional connectivity is found in patients with ESRD, which is associated with cognitive function.

Objective To investigate the clinical curative effect of Danhong injection and Tongxinluo capsule in treating patients with cerebral Infarction. Methods Eighty cerebral infarction patients of Neurology Department in Kailuan General Hospital Affiliated to Hebei United University were selected and randomly divided into control and treatment groups. Patients in the control group were received the based therapy,and patients in treatment group were received Danhong injection and Tongxinluo capsule besides the based therapy. The levels of homocysteine(Hcy),blood lipid,blood viscosity were measured at before treatment,the 14th day,1 month and 3 months after the treatment. All data were analyzed by SPSS13. 0. Results (1)The levels of Hcy,total cholesterol( TC),triglyceride( TG)and blood viscosity( high shear viscosity,low shear viscosity and hematocrit)in treatment group were significantly different from the control group at the 14th day after treatment(P < 0. 05).(2)The levels of TC,TG,HDL-C,LDL-C and blood viscosity in patients of the treatment group at 1 month and 3 months after treatment were different from those of the control group( P< 0. 05). Meanwhile,the levels of TC,TG,HDL-C,LDL-C and blood viscosity in patients of the treatment group at the 14th day after treament were significant different from those of 3 month after treatment(P < 0. 05).(3) The levels of TG,HDL-C,LDL-C and hematocrit in patients of the control group at 3 months after treatment were significantly different from those at pre-treatment(P < 0. 05). The CHOL and TG levels of the control group were different from those at pre-treatment at the 14th day after treatment( P < 0. 05).(4)There were significant differences between two groups at the 14th day,1 month and 3months after treatment in terms of therapy effect(Z= 5. 21,5. 54,3. 86;P = 0. 031,0. 024,0. 048). Conclusion The therapy of Danhong injection combined with Tongxinluo capsule can reduce the levels of Hcy,blood lipid,blood viscosity,and then improve the prognosis of patients with cerebral infarction.

Cinobufacino injection is purified from water extraction of the skin of Bufo bufo gargarizans, which has been widely used for various cancers in clinic with significant anti-tumor effects. Bufadienolides were regarded as the main active constituents of cinobufacino injection in previous reports. In present study, 6 bufadienolides were isolated and purified from Cinobufacino injection. Their structures were identified as 3-epi-ψ-bufarenogin (1), ψ-bufarenogin (2), 3-epi-arenobufagin (3), arenobufagin (4), 3-epi-gamabufotalin (5), and 3-oxo-arenobufagin (6), separately. Among them, 1 and 3 were new compounds, 5 and 6 were new natural products. Compounds 1, 2 and compounds 3, 4 were two pairs configuration isomers at C-3, separately.

Objective To observe the relationship between expression changes of γH2AX and the radiosensitivity of lung cancer cells in vitro. Methods The radiosensitivity of lung cancer cell lines A549 and SBC-3 was measured by clone forming assay. The DSBs damage of lung cancer cell lines A549 and SBC-3 was determined by Western blot assay. Re-sults The clone forming rates of lung cancer cell lines A549 and SBC-3 were gradually decreased with the increased radia-tion dose.γH2AX expression was related to the cell radiosensitivity 1 hour and 6 hours after radiated. Conclusion The phosphorylated histoneγH2AX is a powerful tool to monitor DNA DSBs and to predict the radiosensitivity in lung cancer ra-diotherapy.