Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM).@*METHODS@#The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated.@*RESULTS@#After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity.@*CONCLUSION@#BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

[Functional prediction of Tanreqing Injection in brain diseases].

The study explores the application of Tanreqing Injection into brain components in brain diseases. The components of Tanreqing Injection and its existing components in rat cerebrospinal fluid were qualitatively analyzed by liquid chromatography-mass spectrometry(LC-MS). The possible mechanism of action of Tanreqing Injection into brain on brain diseases was predicted by network pharmacological theory. In this study, 17 brain-entry components of Tanreqing Injection were founded, and 222 core targets were obtained from network pharmacological results. The biological processes include 31 items such as negative regulation of apoptotic process, MAPK cascade, Ras protein signal transduction, and 22 items such as PI3 K-Akt signal transduction, MAPK signal transduction and neurotrophic factor signal transduction. Nine brain diseases including stroke, migraine and meningioma were screened out by predicting the effect of Tanreqing Injection on brain components, which provide ideas and directions for further study of a certain encephalopathy and lay a theoretical foundation for further revealing its molecular mechanism.

[Explore compatibility mechanism of Xingnaojing injection in treating cerebral infarction based on network pharmacology].

This paper aimed to explore the molecular mechanism of Xingnaojing injection and its scientific connotation of compatibility mechanism from a new perspective on bioinformatics and network biology. Based on the analysis function of intergrative pharmacology platform V1.0, the compatibility mechanism of this prescription was investigated by constructing the herbs-compounds-targets network. Seven hundreds and ninety-five targets from the prescription were screened out, then 302 hub nodes were included in drug targets-disease targets network. Enrichment analysis showed that it was related to MAPK cascade, negative/positive regulation of apoptotic process and other biological functions as well as PI3K/AKT, neurotrophin and other signal pathways. The target functions of different drugs were similar, complementing each other, and belonging to the common signaling pathway with asynergistic effect. Based on analysis of core components-key targets-main pathway network, among totally 25 core components and 29 key targets, musk had 15 and 25 respectively.SLC1A2, AR, PGR, CAT, NMDA receptors and other targets were associated with cerebral infarction. Musk, gardenia and borneol compatibility can play a bidirectional regulation of apoptosis; musk and gardenia showed synergistic effect on Ras signaling pathway, indicating that musk was the main ingredient of the injection and the other three drugs played the role of assistance. This study could not only provide the bioinformatics support in compatibility mechanism of Xingnaojing injection, but also provide theoretical support for its formula rationality.

Treatment Selection of Elderly Acute Myeloid Leukemia Patients Guided by HCT-CI Score / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the feasibility of guiding the individalized treatment strategy for elderly AML patients by using hematopoietic cell transplantation-comorbidity index(HCT-CI) score.</p><p><b>METHODS</b>The clinical and biological data of 165 elderly (260 years) AML patients in department of hematology of the first affiliated hospital of Wenzhou medical universtity from January 2000 to December 2014 were analyzed retrospectively. The AML patients were divided into 3 groups: score 0-1, 2-3 and ≥4 according to HCT-CI, then the patients in each group again were divided into standard chemotherapy group, low dose chemotherapy group and support therapy group accoriding to therapeutic regimens, and the efficacy of above mentioned 3 kinds of treatment and their effects on survival of ealderly AML patients were compared, the prognostic risk factors for patients were analyzed further.</p><p><b>RESULTS</b>A total of 165 patients (100%) were followed-up, and the mean follow-up time was 309 days, median survival time was 210 days. The survival analysis showed that the patients in HCT-CI score 0-1 group and 2-3 group banefited from chemotherapy, while the survival analysis of the HCT-CI score ≥4 group showed that there were no significant differance in survival rate between support therapy and chemotherapy groups. The complete remission rate and early mortality of patients received low dose or standard dose chemotherapy in HCT-CI score 0-1, 2-3 and ≥4 groups were not significantly different. Univariate analysis and multivariante analysis of COX ratio risk model showed that the EOCG-PS≥2, WBC≥100×10/L at initial diagnosis and HCT-CI score ≥4 were the independent risk factor affecting the prognosis of elderly AML patients. The median survival time of patients received chemotherapy and support therapy was 840 and 150 d(P<0.01) in HCT-CI score 0-1 group respectively, 210 and 60 days (P<0.01) in HCT-CI score 2-3 group respectively, 130 and 90 days (P>0.05) in HCT-CI score ≥4 group, respectively.</p><p><b>CONCLUSION</b>The HCT-CI score can be used as simple and feasible evaluation criteria to judge the selection of individualized treatment strategy for elderly AML patients.</p>

Construction of anti-cD20scFv/CD80/CD28/zeta recombinant gene modified T cell and research on its targeting cytotoxicity / 中华血液学杂志

<p><b>OBJECTIVE</b>To construct anti-CD20scFv/CD80/CD28/zeta recombinant gene modified T cells, test its effectiveness of eradicating CD20+ lymphoma cells and provide a probably new approach to tumor adoptive immunotherapy.</p><p><b>METHODS</b>CD28-zeta cDNA were amplified from vector pBULLET and inserted into pLNCX vector that contained anti-CD20scFv/CD80 gene. The recombinant vectors were transduced into PA317 cells and high titer retroviruses were obtained to infect human peripheral blood T lymphocytes. Resistant T cells were obtained by G418 selection at one week. Then transduced T lymphocytes and lymphoma cell lines Daudi Raji were cocultured. The cytotoxicity and cytokine production of transduced T cells were determined by non-radio-activation cytotoxicity assay and ELISA respectively.</p><p><b>RESULTS</b>The recombinant eukaryotic vector was constructed successfully as proved by enzyme digestion analysis and sequencing. These T cells were able to lyse CD20+ target cells and secrete high levels of IL-2 and IFN-gamma in vitro.</p><p><b>CONCLUSION</b>Recombinant gene modified T cells can be constructed successfully. It can specially kill CD20 positive lymphoma cells in vitro.</p>

Apoptosis induced by hydroquinone in bone marrow mononuclear cells in vitro / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of hydroquinone on apoptosis of bone marrow mononuclear cells, and to evaluate the toxic effect of benzene on stem cells.</p><p><b>METHODS</b>Cell morphology was observed by HT fluorescent stain method, and DNA fragments were analyzed by agarose gel electrophoresis. Anti-Annexin V FITC plus PI staining for apoptotic and necrotic rate was examined by flow cytometer.</p><p><b>RESULTS</b>After adding different concentrations of hydroquinone to the cells for 6 h culture, the fluorescent intensity of nucleus increased, the color of nucleus became deep and inhomogeneous, and the chromatin was condensed and distributed around the neucleus. DNA ladder was detected in all samples. Cell apoptotic rate in different concentration of hydroquinone groups was significantly higher than that in blank control group (P < 0.05). With the increase of the concentration of hydroquinone, the apoptotic and necrotic rate also increased. The optimal concentration of hydroquinone was 50 micro mol/L. When it was >or= 75 micro mol/L, the necrotic rate increased significantly. Hydroquinone-induced apoptosis was associated with culture time at the concentration of 50 micro mol/L, and the peak apoptotic time was 10 h, then the apoptotic rate decreased and necrotic rate increased.</p><p><b>CONCLUSION</b>Hydroquinone can induce apoptosis of bone marrow mononuclear cells in vitro with dose-effect and time-effect relationship.</p>