Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice / 中国实验血液学杂志

OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.@*METHODS@#THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.@*RESULTS@#1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.@*CONCLUSION@#Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Clinical Study on Middle-late Non-small Cell Lung Cancer Treated with Therapy of Strengthening Qi, Resolving Phlegm and Dissipating Mass / 广州中医药大学学报

Objective To observe the clinical effect of therapy of strengthening Qi, resolving phlegm and dissipating mass for middle-late non-small cell lung cancer. Methods Sixty patients with middle-late non-small cell lung cancer were randomly divided into 3 groups according to the results of intention-to-treat and genetic test. All of the 3 groups were given fundamental supportive and asymptomatic treatment, and additionally Group Ⅰ was mainly given oral use of Jinfuan Decoction with the actions of strengthening Qi, resolving phlegm and dissipating mass based on syndrome differentiation, group Ⅱ was treated with molecular targeted therapy with Gefitinib Tablets and /or Erlotinib Hydrochloride Tablets, and groupⅢ was only given the fundamental supportive and asymptomatic treatment. The 3 groups were treated for 3 cycles(84 days), and then we compared the tumor size, clinical symptoms, quality of life, distant metastasis, and the toxic and adverse effect in each group. Results (1) GroupⅠand group Ⅱhad stronger effect on relieving cough, shortness of breath and lassitude than groupⅢ(P<0.05); groupⅡand groupⅢwere more effective on relieving bloody sputum and chest pain than groupⅠ(P<0.05); groupⅠand groupⅢwere more effective on relieving fever than groupⅡ(P < 0.05). (2) In aspect of quality of life, KPS scores of groupⅠand group Ⅱwere much increased after treatment (P < 0.05), but the scores of group Ⅲ showed no obvious increase (P > 0.05). The improvement of KPS scores in groupⅠand groupⅡwas superior to that in groupⅢ(P<0.05). (3) GroupⅡhad a higher effective rate on stabilizing tumor size, the rate arrived to 65.0％, and was superior to that in groupⅠand groupⅢ(P <0.05) , and the effective rate in group Ⅰ was superior to that in group Ⅲ(P < 0.05). Group Ⅰ and group Ⅱhad a higher stabilizing rate than group Ⅲ(P < 0.05) , but the difference between group Ⅰ and group Ⅱ was insignificant (P>0.05). (4) GroupⅠhad less adverse reaction and higher safety. (5) The distant metastasis rate in groupⅠand groupⅡwas obviously lower than that in groupⅢ(P<0.05), but the difference of distant metastasis rate beetween group Ⅰ and group Ⅱ was insignificant (P > 0.05). Conclusion Therapy of strengthening Qi , resolving phlegm and dissipating mass is effective on relieving tumor-related symptoms , improving the quality of life, stabilizing the tumor, and controlling the distant metastasis in middle-late non-small cell lung cancer patients.

Experience of Professor SUN Xue-mei in Treatment of Primary Thrombocythemia / 中国中西医结合杂志

There is no radical cure for essential thrombocythemia currently. Professor SUN Xue-mei has extensive clinical experience in treating it by combined therapy of Chinese and Western medicine. In this paper, authors tried to summarize her experience from guiding ideology and therapeutic points. Authors insisted on the direction of integrative medicine on the basis of syndrome differentiation, paying attention to psychological counseling,and applied individual treatment in clinics.

Modified Shengma Biejia Decoction Combined with CAG Program for Elderly Acute Myeloid Leuke- mia Patients with Yin Deficiency Toxin Stasis Syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of modified Shengma Biejia Decoction (MSBD) combined with CAG program in treating elderly acute myeloid leukemia (AML) patients with yin deficiency toxin stasis syndrome (YDTSS).</p><p><b>METHODS</b>Totally 46 elderly AML patients were assigned to the treatment group (24 cases; treated with MSBD + CAG) and the control group (22 cases; treated with CAG + placebos of Chinese medicine) according to random digit table. The therapeutic course of CM placebo or MSBD was 21 days. The clinical efficacy and adverse reactions were observed. Meanwhile, physical state (ECOG Score), transfusion dependency, and TCM syndrome score were compared before and after treatment.</p><p><b>RESULTS</b>(1) The complete remission rate was 54% (13/24) and the objective response rate (ORR) was 71% (17/24) in the treatment group, obviously higher than those of the control group [36% (8/22); 54% (13/24)], with statistical difference (P = 0.036, 0.042). When comparing the efficacy based on risk level, the moderate and poor ORR was 71% (10/14) and 67% (6/9) in the treatment group, and 57% (8/14) and 33% (2/6) in the control group, with statistical difference between the two groups (P = 0.048; P = 0.010). (2) Compared with before treatment in the same group, the ECOG score significantly decreased, the average infusion time of red cells and platelets were markedly prolonged in the treatment group after treatment (P < 0.05). ECOG score, the average infusion time of red cells and platelets were significantly better in the treatment group than in the control group after treatment (P < 0.05). (3) Compared with before treatment in the same group, scores of fever, hemorrhage, and bone pain were markedly reduced in the control group (P < 0.05); scores of fever, fatigue, hemorrhage, dry mouth, and bone pain were markedly reduced in the treatment group (P < 0.05). Better effect in relief of fever, fatigue, hemorrhage, dry mouth, and so on was obtained in the treatment group than in the control group (P < 0.05). (4) In aspect of hematotoxicity, the incidence of neutropenia, anemia, thrombocytopenia was obviously lower in the treatment group than in the control group [29.2% (7/24) vs 54.5% (12/22); 16.7% (4/ 24) vs 45.5% (10/22); 33.3% (8/24) vs 63.6% (14/22); P < 0.05]. The incidence of fatigue and anorexia was obviously lower in the treatment group than in the control group [37.5% (9/24) vs 63.6% (14/22), 37.5% (9/24) vs 81.8% (18/22); P < 0.05].</p><p><b>CONCLUSION</b>MSBD combined with CAG program in treating elderly AML patients with YDTSS, with efficacy enhancing toxicity reducing effect, had distinct advantages in improving physical condition and clinical symptoms, and reducing transfusion dependency.</p>