Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

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

OBJECTIVE: To observe the safety of donor NK cell infusions in the settings of hematopoietic stem cell transplantation and after consolidation chemotherapy in elderly patients with acute myeloid leukemia (AML). METHODS: Forty patients with AML were included, in which 21 patients aged over 60 years were at the stage of complete remission (CR) and 19 patients that received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononucleated cells were isolated from peripheral blood from the donors (for allo-HSCT) or healthy immediate family members (elderly AML). The cells were seeded into the flasks pre-coated with NK cell specific activators, and expanded in media containing recombinant human IL-15 and IL-2 for 14 days. The cells were transfused intravenously after the identification of quality control. Trypan blue exclusion test was used for the determination of cell viability and counting. Flow cytometry analysis was performed to assess the surface antigenic profile. Seventy-eight infusions of the cell products were received by the elderly patients with AML after consolidation chemotherapy, 11 infusions were received by the patients during allo-HSCT and 32 infusions 3 moths after transplantation. The safety of cell therapy, body temperature, blood pressure and other indexes were observe during and 48 hours after cell transfusion. Meanwhile, the occurrence and severity of acute graft-versus-host disease (GVHD) were documented. RESULTS: Flow cytometry analysis showed that the proportion of NK cells (CD3^-CD56⁺) in the mononucleated cells before culture was (14.10±4.22)% (n=121), and the proportion increased dramatically up to (87.29±8.75)% (n=121) after culture for 14 days, the number of NK cells increased to 753.47±140.13 times (n=121). The doses of the infused NK cells was (7.58±2.50)×10⁷/kg per infusion. Moderate fever occurred in three cases after multiple infusions, and the temperature restored to normal on the same day after treatment. Fever was observed in one patient after every infusion of four times in total. The temperature reached to 38.5-39.0 ℃ and returned to normal within 1-2 hours after adequate antipyretic treatment, and then there was no discomfort. No GVHD was observed in the elderly AML patients, while 6 cases that received allo-HSCT developed moderate acute GVHD, among them grade I in 5 cases and grade II in 1 case. No other severe toxicities were observed. CONCLUSION NK cell products with a high-purity could be obtained by ex vivo expansion with this protocol. The transfusion of these expanded cells is generally safe in the elderly patients with AML that have received chemotherapy or patients that received hematopoietic stem cell transplantation.
Aged ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/therapy* ; Middle Aged ; Recurrence

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 effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80⁺CD86⁺ cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively. RESULTS: The proportion of CD80⁺CD86⁺ cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group. CONCLUSION For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.
Cell Differentiation ; Cells, Cultured ; Dasatinib/pharmacology* ; Dendritic Cells ; HLA-DR Antigens/pharmacology* ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Leukocytes, Mononuclear ; Monocytes

OBJECTIVE: To evaluate the risk factors affecting thromboembolism in lymphoma patients with chemotherapy. METHODS: Three hundred and four consecutive lymphoma patients treated by chemotherapy between January 2012 and July 2019 were enrolled and retrospectively analyzed, consisting of 111 patients with thromboembolism and 193 without thromboembolism. Univariate analysis was used to compare the clinical characteristics and related laboratory examination between the patients, while multivariate Logistic regression analysis were used to identify the risk factors affecting thromboembolism in lymphoma patients with chemotherapy. RESULTS: Univariate analysis showed that the female, BMI <18.5 or >24, ≥60 years old, with abnormal platelets before chemotherapy, prolonged single hospitalization days and patients at Ann Arbor stage III and IV could increase the incidence of thromboembolism in lymphoma patients treated by chemotherapy. Multivariate Logistic regression analysis showed that abnormal platelet count before chemotherapy, patients at Ann Arbor stage III and IV, and female were all the independent risk factors affecting thromboembolism in lymphoma patients thromboembolism after chemotherapy (P<0.05). CONCLUSION For lymphoma chemotherapy patients, female, abnormal platelet count before chemotherapy and Ann Arbor stages III and IV show a significantly higher risk for thromboembolism. Thus, preventive anticoagulation therapy is recommended.
Antineoplastic Combined Chemotherapy Protocols ; Female ; Humans ; Lymphoma/drug therapy* ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Thromboembolism/epidemiology*

OBJECTIVE: To investigate the role of petroleum ether extract of Rhizoma Amorphophalli (SLG) in inhibiting proliferation and promoting apoptosis and differentiation of leukemia K562 cells. METHODS: K562 cells were processed by SLG and PD98059 which was the ERK signaling pathway blocker. Then cell vitality was tested by MTT. Cell apoptosis rate and positive percentage of antigen expression related with differentiation were detected by flow cytometry. The protein expression levels of ERK1/2 and pERK1/2 were detected by Western blot. RESULTS: The proliferation activity of K562 was reduced by 50, 100, 200 mg/L SLG in a concentration dependent manner (r=0.9997). The apoptosis rate and positive expression rate of CD11b, CD14 and CD42b which were related with differentiation were raised by SLG, as well as the expression of pERK1/2, while PD98059 could reverse the promoting effect of SLG on apoptosis and differentiation partially. CONCLUSION SLG can inhibit the proliferation and promote apoptosis and differentiation of K562 cells through ERK signaling pathway.
Alkanes ; Apoptosis ; Cell Proliferation ; Humans ; K562 Cells ; Petroleum ; Plant Extracts/pharmacology*

OBJECTIVE: To investigate the clinicopathological features of intestinal diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical features, pathological morphology, immunophenotype, and EBER in situ hybridization of 136 DLBCL patients diagnosed in Jinan People's Hospital Affiliated to Shandong First Medical University from January 2007 to October 2014 were analyzed retrospectively. A total of 136 DLBCL samples were obtained, the DLBCL sites were categorized as: duodenum (n=23), ileocecal region (n=63), other small intestine (n=29), rectum (n=7), and other large intestine (n=14). Survival curves for the DLBCL patients were plotted using the Kaplan-Meier method and judged by the Log-rank test. RESULTS: Patients with DLBCL of the ileocecal region and other small intestine except duodenum were mainly male (P=0.042), and had a higher proportion of limited-stage tumors(P=0.015), and lower International Prognostic Index (IPI) (P=0.001). Patients with DLBCL of ileocecal region had higher incidence of lactate dehydrogenase elevation (P=0.007), and higher incidence of intestinal obstruction or perforation (P<0.001) than those with DLBCL of other regions. The 5-year overall survival and 5-year progression-free survival of patients with DLBCL in ileocecal and other small intestine sites were higher than those in other sites, but the differences were not statistically significant (P=0.135, 0.459). Fifty percent of intestinal DLBCL were germinal center B cell-like (GCB) subtypes. A low-grade B-cell lymphoma was found in 21% of 136 tumor samples. In ileocecal and other small intestinal specimens, the proportion of low-grade B-cell lymphoma was 29%, and the difference was statistically significant(P=0.025). About 16% of 136 DLBCL samples expressed follicular lymphoma while no mucosa-associated lymphoid tissue lymphoma . The Epstein-Barr virus-encoded RNA-1 (EBER1) positive rate of duodenal DLBCL was significantly higher than that of other sites (5/23, 22% vs 2/63, 3%, P=0.001). CONCLUSION The intestinal DLBCL is commonly observed in male, and ileocecal is the most primary site. Patients with DLBCL of the ileocecal region and small intestine except duodenum have low IPI, high proportion of limited-stage tumors, low level of lactate dehydrogenase, high incidence of intestinal obstruction or perforation, and low incidence of inert lymphoma. The EBER1 positive rate of DLBCL in duodenal is higher.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Prognosis ; Retrospective Studies

OBJECTIVE: To establish a mouse mixed chimerism (MC) model of nonmyeloablative allogeneic bone marrow transplantation(allo-BMT) and explore its affecting factors. METHODS: The MC model was established by nonmyeloablative allo-BMT followed by high-dose post-transplant cyclophosphamide (PTCY). 123 mice in the experiments was retrospectively analyzed, and the factors related with the chimerism were explored with the univariate and multivariate logistic regression analysis. A multivariate linear regression was performed by R project to obtain a mathematical model for predicting the chimeric level with relevant affecting factors. RESULTS: The model presented mixed chimerism on day 14 after transplantation, and was characterized by a donor lymphocyte infusion (DLI) which significantly promoted donor engraftment on day 15, but transfplantation of PBS in control group was failed. Among 123 mice, 47 (38.21%) mice were MC, while 76 (61.79%) mice were non-MC in 123 mice, respectively; univariate analysis showed that the baseline body weight of mice (P=0.001, 17.84±1.19 g vs 18.50±0.94 g), total body irradiation(TBI，P=0.048) and the using of cyclophosphamide (P=0.16) were affected the chimeric state of mice, while the number of infusing cells and the time of detection showed no significant effects. Multivariate regression analysis showed that under certain conditions, the body weight of mice on day 0 was an independent factor affecting chimeric levels (OR=0.493, 95% CI 0.307-0.791, P=0.003). Through R project multiple linear regression, the math model was achieved, which was chimerism=6.09-12×weight(g)+80.03×TBI(Gy)-4.4×cell-counts (× 10 CONCLUSION The experiment presents a method for establishing a mixed chimeric mice model after non-myeloablative bone marrow transplantation and constructs a mathematical model with relevant factors affected chimerism status.
Animals ; Bone Marrow Transplantation ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Mice ; Retrospective Studies ; Transplantation Chimera ; Transplantation Conditioning ; Transplantation, Homologous