[The Research Progress in the Diagnosis and Treatment of Primary Intestinal Diffuse Large B-cell Lymphoma--Review].

Primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is clinically rare, but in recent years, with the gradual maturity of pathology and molecular biology technology, its incidence rate and diagnosis rate have also increased. Due to the lack of specificity of the clinical symptoms of PI-DLBCL, it is easy to misdiagnose and miss the diagnosis, and there is no consensus on the best treatment of PI-DLBCL in clinical practice. Therefore, by retrieving the latest literature at home and abroad, this review systematically discusses the pathogenesis, clinical manifestations, diagnostic criteria, treatment and prognosis of PI-DLBCL, in order to improve the understanding of rare PI-DLBCL in hematology and oncology, and provide reference for basic research and clinical diagnosis and treatment of PI-DLBCL.

[Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors].

OBJECTIVE: To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. METHODS: Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). RESULTS: Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). CONCLUSION: Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

[The Mechanisms of Piceatannol in Inhibiting the Malignant Biological Characteristics of Acute Myeloid Leukemia Cells].

OBJECTIVE: To explore the effect and molecular mechanism of Piceatannol on malignant biological characteristics of acute myeloid leukemia (AML) cells. METHODS: HL60, U937, HL60/ADR and U937/ADR cells were treated with different concentrations of Piceatannol. CCK-8 assay was used to detect cell proliferation. Cell apoptosis was detected by flow cytometry with Annexin V/PI double staining. The protein expressions of apoptosis, autophagy and related signaling pathways were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression changes of drug resistance genes in drug-resistant AML cell lines. RESULTS: The activity of HL60 and U937 cells could be inhibited by Piceatannol and induced apoptosis. When Piceatannol interfered with AML cells for 24 h, the ratio of autophagy marker LC3-II/LC3-I increased with the increase of concentration (r=0.672， r=0.549). When Piceatannol interfered with AML cells for 48 h, the expression of Bcl-2 protein was down-regulated and caspase-3 was hydrolyzed and activated. At the same time, the activation level of Akt/NF-κB signaling pathway was inhibited to induce programmed death of AML cells. Piceatannol can also down-regulate the expression of MRP1 and gradually weaken the chemotherapy resistance of AML drug-resistant cell lines, but it has a weak effect on the expression of BCRP and almost no effect on MDR1. CONCLUSION: Piceatannol can inhibit the proliferation of AML cells and induce programmed death, which may be related to the inhibition of Akt/NF-κB signaling pathway, the hydrolysis of caspase-3 and the down-regulation of Bcl-2 protein expression, and the suppression of the expression of some drug resistance genes.

[Experimental Study on the Mechanism of Mangiferin Inhibiting Malignant Biological Characteristics of Multiple Myeloma and Exerting Anticancer Effect].

OBJECTIVE: To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy. METHODS: U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family. RESULTS: Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05). CONCLUSION: Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.

[The Effects and Regulatory Mechanism of Targeting CXC Chemokine Receptor 1/2 Combined with Ara-C on the Malignant Biological Behaviors of U937 Cells of Acute Myeloid Leukemia].

OBJECTIVE: To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML. METHODS: Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05). CONCLUSION: Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.

Private post-secondary library websites and the ADA: compliancy and COVID-19.

This study explores whether US post-secondary institutions (PPI) follow philosophies to foster inclusive communities, providing resources for those individuals with disabilities thrive socially, personally, and academically, while there have been no thorough studies conducted to determine web accessibility of the nation's top-ranked PPI library webpages. Additionally, this study pioneers in comparison with the accessibility of PPI's library homepages fighting COVID-19. The study evaluated the library homepages of the premium PPIs based on Money.com's 2019 list of "The Best Colleges in America" via the WAVE web accessibility evaluation tool. The outcomes determined that most of the library homepages analyzed were littered with numerous errors, and the shift to online-based research in learning had no significant impact on the number of errors WAVE detected. The disconcerting findings of this study demonstrate the overall failure to recognize the importance of web accessibility or perhaps even the indifference toward accessibility on the part of the PPI community.

[The Value of T Cell subsets and Cytokine Levels Changes in the Clinical Diagnosis, Treatment and Prognosis Evaluation of Multiple Myeloma].

OBJECTIVE: To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with MM and immune function status, biochemical indicators, and their relationships with clinical stage and prognosis, which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of MM patients. METHODS: The clinical data of 89 MM patients in two hospitals were collected, and 36 healthy people without tumor or infectious diseases were selected as the control group. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels, respectively. At the same time, automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (ALB), creatinine (CRE) and hemoglobin (HGB) levels, and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed. RESULTS: The proportions of NK cells and CD8+T lymphocytes in the peripheral blood of MM patients were significantly higher than that of the control group (P<0.01), the proportion of CD4+T and the ratio of CD4+/CD8+ were lower than those of the control group (P<0.05); however, there was no significant difference in the numbers CD3+T cells compared with the control group (P>0.05). The proportion of CD4+T and ratios of CD4+/CD8+ in MM patients were lower than those of normal controls, and were negatively correlated with MM staging (r=-0.964, r=-0.653), that is, the later the MM staging, the more obvious their levels were reduced, while CD8+T and NK cells were positively correlated with MM staging (r=0.891, r=0.728), that is, the later the MM staging, the more significant their levels increased. The levels of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) of MM patients in the disease stage Ⅰ, Ⅱ and Ⅲ were (5.87±0.92)%, (7.97±1.32)%, (11.52±4.71)% respectively, the difference was statistically significant compared with control group (P<0.05), and the level of Treg cells in MM patients with stage III was significantly higher than that in controls and patients with other disease stages (P<0.01). The proportion of Treg cells (CD4+CD25highCD127low/-T cells/CD4+T cells) in MM patients was positively correlated with the concentration of ß2-MG and LDH (r=0.793, r=0.536), but had no significant correlation with HGB, ALB and CRE. The serum levels of IL-6, IL-10 and TNF-α in MM patients were significantly higher than those in the control group (P<0.05), which were closely related to MM staging(r=0.839, r=0.917, r=0.746), that is, the later the MM staging, the higher the levels; The serum IFN-γ level was negatively correlated with the stage of MM (r=-0.689), and its level gradually decreased with the increase of the disease stage and degree (P<0.01). There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage, but they were all up-regulated compared with the control group (P<0.05). CONCLUSION: The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of MM patients, which is an effective indicator for the disease monitoring of MM patients.

[Clinical Features of Two Cases of Rare Mast Cell Leukemia].

Mast cell leukemia(MCL)is an extremely rare type of leukemia with high heterogeneity in clinical practice.MCL needs to be diagnosed by means of bone marrow routine and pathology,flow immunophenotyping,and cytogenetics and molecular biological testing.This article retrospectively studied the clinical data including the clinical features,diagnosis,treatment,and prognosis of two patients with MCL,aiming to improve the understanding of MCL and provide a new reference for the clinical diagnosis,treatment,and basic medical research of this disease.

[Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report of One Case].

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.