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.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

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.
Humans ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/genetics* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Lipopolysaccharides/pharmacology* ; NF-kappa B

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

OBJECTIVE: To evaluate the efficacy of the second-line nilotinib and third-line dasatinib on chronic myelogenous leukemia (CML) with failed first- and second-line treatments, and analyze the influencing factors of the efficacy. METHODS: Selected 83 patients in The Third People's Hospital of Kunshan City, Jiangsu Province with CML who were treated with nilotinib as the second-line treatment after the failure of the first-line treatment with imatinib as the second-line treatment group (referred to as the second-line group) from January 2014 to December 2018, and 61 CML patients who were treated by dasatinib as the third-line treatment group (referred to as the third-line group) after the failure of the second-line treatment with nilotinib; the first-line treatment with imatinib failed, but due to various reasons, the patients were fully after being informed of the possible serious consequences of not changing the drug treatment, 37 CML patients who were still required to continue imatinib treatment served as the control group. The hematological, genetic and molecular responses of each group were compared for 3, 6, and 24 months of treatment. LogistiC regression was used to analyze the factors affecting the second and third line curative effects. RESULTS: The three groups had statistically significant differences in the rates of achieving CHR, MCyR, and MMR at 3, 6, and 12 months of treatment (P<0.05). Compared the two groups, the CHR rates of the second-line group at 3, 6, and 12 months of treatment were 100.00%, 97.59%, and 95.18%, respectively; higher than the third-line group's 90.16%, 86.89%, 83.61% and the control group's 83.78%, 75.68% and 72.97%; the CHR rate of the third-line group was higher than that of the control group at 6 and 12 months of treatment. The rates of reaching MCyR at 3, 6, and 12 months after treatment in the second-line group were 87.95%, 93.98% and 93.98%, respectively, while those in the third-line group were 80.33%, 88.52% and 86.89%, which were higher than those of the control group of 67.57%, 64.86% and 48.65%. The rates of achieving MMR at 3, 6, and 12 months of treatment in the second-line group were 19.28%, 33.72% and 60.24%, respectively, and those in the third-line group were 11.48%, 26.23% and 49.18%, which were higher than those of the control group of 0.00%, 2.70% and 0.00%; The rate of reaching MMR within 12 months of treatment in the second-line group was higher than that of the third-line group, and the differences was statistically significant (P<0.05). There was no significant difference in the rate of reaching MCyR between the second-line group and the third-line group at 3, 6, and 12 months, and the rate of reaching MMR at 3 and 6 months (P>0.05). The incidence of nausea and vomiting among the three main non-hematological adverse reactions, and the incidence of grade 1~2 anemia among the hematological adverse reactions were statistically significant (P<0.05). There was no significant difference in the incidence of rash, eyelid edema, diarrhea, thrombocytopenia, leukopenia and neutropenia in the three groups (P>0.05). The incidence of nausea and vomiting and grade 1~2 anemia in the second-line group and the third-line group were higher than that of the control group, and the difference was statistically significant (P<0.05). There were statistically significant differences in Sokal score, medication compliance, and hematological adverse reactions between the MMR group and the non-MMR group (P<0.05). Logistic regression analysis showed that dose reduction or withdrawal during the treatment period, and grade 3~4 hematological adverse reactions were the main factors affecting the second and third line curative effects (OR=22.160, 2.715, 95% CI=2.795-93.027, 1.882-48.834). CONCLUSION The second-line nilotinib and the third-line dasatinib have a better effect on CML patients who have failed the first and second-line treatments. Grade 3~4 hematological adverse reactions, dose reduction or withdrawal are risk factors that affect the efficacy of second and third-line treatments.
Antineoplastic Agents/therapeutic use* ; Dasatinib/therapeutic use* ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors/therapeutic use* ; Pyrimidines/therapeutic use* ; Treatment Outcome

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.
B-Cell Maturation Antigen ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen ; Remission Induction

Neutrophil extracellular trap (NET) is a type of bead-like, fibrous and reticular substances that is actively released by activated inflammatory neutrophils during the stage of infections or inflammatory responses. NET, which is composed of chromatin DNA and multiple intracellular protein components, may wrap pathogens to limit their diffusions. Meanwhile, NET may kill pathogens via a wide range of antibacterial proteins, which is considered as the third antibacterial mechanism of neutrophils, in addition to phagocytosis and degranulation. Recent studies have shown the involvement of NET in the immune response against parasitic infections. This review summarizes the advances of NETs in the immune responses against parasitic infections, so as to provide insights into the elucidation of the pathogenesis and development of therapeutics of parasitic diseases.

OBJECTIVE: To evaluate the predictive value of pre-treatment serum uric acid (sUA) level for the prognosis of newly diagnosed multiple myeloma (NDMM) patients. METHODS: The NDMM patients admitted to our center from January 2014 to December 2018 were analyzed retrospectively, and 94 patients among them who were initially treated with bortezomib-based chemotherapy for at least 4 cycles were included in this study. Clinical characteristics, laboratory data and follow-up information were collected, and the predictive value of sUA on the overall survival (OS) of NDMM was evaluated by using receiver operating characteristic (ROC) curve based on the patient's pre-treatment sUA level and the survival status at the end of follow-up, and the correlation of the sUA level with patient's clinical, laboratory characteristics and overall survival (OS) was further analyzed. The univariate and multivariate Cox proportional-hazards model were used to identify the potential factors affecting OS. RESULTS: ROC analysis showed that the area under the curve for predicting OS in NDMM patients with sUA level was 0.702 (P<0.001), and the optimal cut-off value was 455.4 μmol/L. Compared to patients with low sUA (<455.4 μmol/L), patients with higher sUA (≥455.4 μmol/L) were more likely to have international staging system (ISS) stage III disease, beta2-microglobulin (β CONCLUSION Pre-treatment sUA level is a potential biomarker for the prognosis evaluation in NDMM patients, which deserves a further exploration and verification.
Bortezomib ; Humans ; Middle Aged ; Multiple Myeloma ; Prognosis ; Retrospective Studies ; Uric Acid

OBJECTIVE: To investigate the irregular antibody positive rate and antibody specificity in children with thalassemia received long-term blood transfusion in Hainan area and analyze the causes of antibody screening positive. METHODS: Micro-column gel method was used to screen the irregular antibody in 49 children who received transfusion treatment in our hospital, and the antibody specificity of the positive samples was evaluated. RESULTS: Fourteen of 49 cases showed positive for screening. Among them, 11 cases showed Rh blood group antibody after detecting antibody specificity, 1 case showed the coexistence of irregular antibody and autoantibody. One case for anti-JK CONCLUSION Most of the antibodies produced after long-term blood transfusion in the children with thalassemia belong to Rh blood group antibodies; the children with mixed thalassemia are more likely to produce antibodies; the antibody screening positive rate of Li nationality is higher than that of Han nationality, which may be caused by the genetic difference of blood type between Li nationality and Han nationality.
ABO Blood-Group System ; Blood Grouping and Crossmatching ; Blood Transfusion ; Child ; Female ; Humans ; Infant ; Male ; Rh-Hr Blood-Group System ; beta-Thalassemia

OBJECTIVE: To explore the effect of miR-144 to the biological behavior of multiple myeloma cells and its mechanism. METHODS: RT-PCR was used to detect the expression of miR-144 in multiple myeloma cells and plasma of MM patients. MTT assay was used to detect the proliferation and cloning ability of myeloma cells transfected by miR-144. Flow cytometry was used to detect the cell cycle distribution of myeloma cells with over-expression of miR-144. Apoptosis of myeloma cells with over-expression of miR-144 was detected by TUNEL assay. Transwell cell invasion and migration assay was used to detect the invasion and migration ability of myeloma cells with overexpressing on miR-144.Western blot analysis was used to detect the protein expression levels of MMP-9 and MMP-2 in myeloma cells with over expression of miR-144, as well as the expression levels of proteins related to Wnt/β-catenin signaling pathway. RESULTS: The expression level of miR-144 in MM cell lines and blood of MM patients was significantly lower than that in control group (P＜0.05). The proliferation, invasion and migration of myeloma cells with over-expression of miR-144 were significantly decreased (P＜0.05), and the apoptosis level was increased (P＜0.05). The expression levels of MMP-9, MMP-2, Wnt/β-catenin signaling pathway in myeloma cells with over-expression of miR-144 were significantly lower than those in control group (P＜0.05). CONCLUSION MiR-144 can inhibit the proliferation, migration and invasion of multiple myeloma cells and induce cell apoptosis. The specific mechanism may be related with the activity of inhibiting Wnt/β-catenin signaling pathway.
Apoptosis ; Biological Products ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; Multiple Myeloma ; Wnt Signaling Pathway ; Wnt4 Protein ; beta Catenin

OBJECTIVE: To investigate the effect of chidamide on the killing activity of NK (Natural killer cell, NK) cells targeting K562 cells and its related mechanism. METHODS: K562 cells were pretreated with chidamide at different concentrations and cocultured with NK cells at different effect-target ratios. The killing effect of chidamide on K562 cells by NK cells, the expression of natural killer group 2 member D (NKG2D) ligands and apoptosis rate of K562 cells were detected by flow cytometry. RESULTS: The killing sensitivity of NK cells to K562 cells could be enhanced by chidamide. The expression of ULBP2 on K562 cell surface could be up-regulate, however, the expression of ULBP1 and MICA/MICB showed no statistically difference as compared with control group. Chidamide showed no obvious cytotoxicity to K562 cells. CONCLUSION Chidamide can significantly improve killing efficiency of NK cells on K562 cells, which may be related to the up-regulation of ULBP2 expression.
Aminopyridines ; Benzamides ; GPI-Linked Proteins ; Histocompatibility Antigens Class I ; Humans ; Intercellular Signaling Peptides and Proteins ; K562 Cells ; Killer Cells, Natural ; immunology ; NK Cell Lectin-Like Receptor Subfamily K