OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m² d1 + oxaliplatin 100 mg/m² d 1 + etoposide 60 mg/m² d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
Humans ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies ; Etoposide ; Neoplasm Recurrence, Local/drug therapy* ; Asparaginase ; Deoxycytidine ; Lymphoma, T-Cell, Peripheral/drug therapy* ; Lymphoma, Extranodal NK-T-Cell/therapy* ; Oxaliplatin/therapeutic use*

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.
Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Humans ; Life Style ; Twins/genetics* ; Twins, Dizygotic ; Twins, Monozygotic

OBJECTIVE: To investigate the prognostic evaluation value of neutrophil-lymphocyte ratio (NLR) in patients with newly diagnosed angioimmunoblastic T cell lymphoma (AITL). METHODS: Clinical data of 39 patients with newly diagnosed AITL in our hospital from March 2010 to August 2018 were colleated and retrospective analyzied, and the relationship between NLR before treatment and the prognosis of AITL patients was analyzed. RESULTS: Among 39 AITL patients, the median value of NCR was 5.43. Based on the cut-off value (5.43), all the patients were divided into 2 groups: high NLR group (5.43, n=20) and a low NLR group (＜5.43, n=19). The total effective rate of treatment was lower in the high NLR group as compered with low NLR group (P=0.041). Univariate analysis showed that, age ＞60 years old, extranodal involvement＞1 as well as high NLR were the independent risk factors that affected overall survival (OS) in newly diagnosed AITL patients. Multivariate Cox analysis showed that extranodal involvement＞1 and high NLR were the independent risk factors that affected OS in newly diagnosed AITL patients. CONCLUSION The NLR may be an independent prognostic factor in patients with newly diagnosed AITL. High NLR associated with poor prognosis.
Humans ; Lymphocytes ; Lymphoma, T-Cell ; Middle Aged ; Neutrophils ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

OBJECTIVETo explore the effect of infusing G-CSF mobilized recipient spleen cells at different time after haploidentical stem cell transplantation(HSCT) on graft-versus-host disease (GVHD) in mice and its possible mechanism.

METHODSForty mice after HSCT were randomly divided into 4 groups (n=10): GVHD positive control group (control group), 1st d recipient cell infusion group after transplantation (+1 d group), 4th d recipient cell infusion group after transplantation(+4 d group), 7th d recipient cell infusion group after transplantation(+7 d group). The mice in control group were injected the normal saline of same equivalent with experimental group which were given the same amount of G-CSF-mobilized recipient spleen cells. The general manifestation and pathological change of GVHD were observed. The expression changes of CD3CD4, CD3CD8cell subsets and FasL in peripheral blood were detected by flow cytometry.

RESULTSThe incidence of GVHD was significantly decreased in +4 d group and the median survival time was longer than 60 days, which was significantly higher than that of control group (24 d), +1 d group (21 d), +7 d group (28 d). (P<0.01, P<0.01, P<0.01). The Fasl expression of peripheral blood T lymphocytes in +4 d group were significantly lower than that in the other 3 groups(P<0.05).

CONCLUSIONThe +4 d infusion of G-CSF mobilized recipient spleen cells on 4th day after haploidentical HSC transplantation can inhibit the expression of FasL in donor T lymphocytes, and significantly reduce the incidence of GVHD.

OBJECTIVETo investigate the effects of microvesicles(MV) isolated from human peripheral blood hematopoietic stem cells(PB-HSC) on immune regulation and hematopoiesis.

METHODSPB-HSCs were separated by density-gradient centrifugation and cultrued. The supernatants of PB-HSC at 48 h were harvested for isolation and purification of MV by using ultracentrifugation. The electron microscopy was used to observe the morphology of MV. The protein level in MV was quantified through bicinchoninic acid(BCA) protein assay. Flow cytometry was used to detect the immunophenotype of MV. Human peripheral blood mononuclear cells(PB-MNC) were isolated from healthy donor and treated with isolated MV. After being co-cultured for 12 h, confocal microscopy was used to observe the action mode of MV on PB-MNC. After being co-cultured for 48 h, the levels of IL-2, IL-6, IL-8, IL-10, IFN-γ and TNF-α were detected by ELISA. Flow cytometry was used to detect the changes of T cell subsets and the activation of T cell subsets as well as intracellular cytokine staining after co-culture for 48 h. The methylcellulose was used to assess the hematopoiesis-supportive function of MV as well as co-cultured supernatants.

RESULTSThe eletron microscopy revealed that MV were elliptical membrane vesicles. The protein amount in MV ranges from 29 to 110 µg. Flow cytometry showed that MV expressed mix markers on the surface, especially highly expressed MV specific marker CD63(85.86%) and hematopoietic stem cell marker CD34(33.52%). After being co-cultured for 12 h, confocal microscopy showed that MV were merged with PB-MNC. After being co-cultured for 48 h, ELISA showed that the secretion of cytokines IL-6,IL-8, IL-10 as well as TNF-α was increased while the level of IL-2 and IFN-γ was not changed much. The results of flow cytometry showed that there was no significant change in T cell subsets and T cell activation. Staining of intracellular factor showed that IL-8 was increased significantly in CD11ccells. The colony-forming experiments revealed that MV and the co-cultured supernatants could facilitate the colony formation.

CONCLUSIONMV isolated from PB-HSC have immune-regulatery function and can prornote hematopoiesis.

OBJECTIVETo investigate the role of α-enolase (ENO1) in regulating glucose metabolism and cell growth in human glioma cells.

METHODSGlucose uptake and lactate generation were assessed to evaluate the changes in glucose metabolism in human glioma U251 cells with small interfering RNA (siRNA)-mediated ENO1 knockdown. MTT assay and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to examine the cell growth and cell cycle changes following siRNA transfection of the cells.

RESULTSTransfection of U251 cells with siRNA-ENO1 markedly reduced glucose uptake (P=0.023) and lactate generation (P=0.007) in the cells and resulted in significant suppression of cell proliferation (*P<0.05) since the second day following the transfection. Transfection with siRNA-ENO1 also obviously suppressed cell cycle G1/S transition in the cells (P=0.0425). The expressions of HK2 and LDHA, the marker genes for glucose metabolism, were significantly down-regulated in the cells with siRNA-mediated ENO1 knockdown.

CONCLUSIONENO1 as a potential oncogene promotes glioma cell growth by positively modulating glucose metabolism.

Acute myeloid leukemia is most common in the elderly patients, and the most elderly patients are thought to be unfit for intensive treatment because of the risk of fatal toxicity, and required other therapeutic approaches to optimize clinical outcome for them. Domestic and foreign scholars have carried out a lot of new drugs and treatment programs. This review focuses on the advances of therapy for elderly acute myeloid leukemia, including biological characteristics of elder AML, adoptive immunotherapy, allogeneic hematopoietic stem cell transplantation and so on.

OBJECTIVETo explore the biological characteristics of microvesicles(MV) derived from bone marrow mesenchymal stem cells (BM-MSC) and their capability supporting ex vivo expansion of hematopoietic stem cells(HSC).

METHODSThe MV from cultured BM-MSC supernatant were isolated by multi-step differential velocity contrifugation; the morphological characteristics of MV were observed by electron microscopy with negative staining of samples; the protein level in MV was detected by using Micro-BCA method; the surface markers on MV were analyzed by flow cytometry. The peripheral blood HSC(PB-HSC) were isolated after culture and mobilization; the experiment was diveded into 2 group: in MV group, the 10 mg/L MV was given, while in control group, the same volume of PBS was given; the change of PB-HSC count was observed by cell counting; the change of surface markers on PB-HSC was detected dynamically by flow cytometry; the cell colony culture was used to determin the function change of PB-HSC after co-culture with MV.

RESULTSMSC-MVs are 20-100 nm circular vesicles under electron microscope. About 10 µg protein could be extracted from every 1×10MSC. The flow cytometry showed that CD63 and CD44 were positive with a rate of 96.0% and 50.2%, while the HLA-DR, CD34, CD29 and CD73 etc were negative. When being co-cultured with GPBMNC for 2 days, the cell number of MV groups was 1.49±0.15 times of the control group (P>0.05). When being co-cultured for 4 days, the cell number of MV groups was 2.20±0.24 times of the control group(P<0.05). The CD34cell number of MV groups was 1.76±0.30 times the control group after culture for 2 day and 1.95±0.20 times after culture for 4 day.

CONCLUSIONThe MV has been successfully extracted from MSC culture supernatant by multi-step differential velocity centrifugation. MSC-MV can promote HSC expansion in vitro.

OBJECTIVETo explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML).

METHODSA total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery.

RESULTSOut of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2.

CONCLUSIONThe CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.

Adolescent ; Adult ; Agranulocytosis ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cladribine ; therapeutic use ; Cytarabine ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Thrombocytopenia ; Topotecan ; therapeutic use ; Young Adult