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Background: Recent studies have suggested association between the ABO blood group and inflammation, which was a crucial pathological process of primary knee osteoarthritis. The aim of this study was to investigate the association between the ABO blood group and primary knee osteoarthritis ​and the severity of primary knee osteoarthritis evaluated by the Kellgren/Lawrence score, as well as the histopathologic association in a subgroup of patients. Methods: We performed a retrospective review of patients with primary knee osteoarthritis that served as the case group ​and a random sampling of healthy blood donors that served as the control group. The severity of knee osteoarthritis at the first outpatient visit was evaluated by the Kellgren/Lawrence scoring system. Further study was performed to investigate the expression of blood group antigens in synovial tissue of the knee in both cases and controls. Results: A total of 1126 cases and 30299 controls were involved. The proportion of AB blood group was higher in the case group than in the control group (9.7% vs. 7.8%), and logistic regression revealed that the AB blood group was a risk factor of primary knee osteoarthritis (P ​= ​0.025 and 0.048 for univariate and multivariate analysis, respectively), independent of age (P ​= ​0.973) and sex (P ​= ​0.520). Patients of the blood group AB had a higher Kellgren/Lawrence score (P ​= ​0.017). The immunohistochemical study indicated association between LeY antigen and primary knee osteoarthritis (P ​= ​0.029). Conclusions: This study suggested that the blood group AB was associated with primary knee osteoarthritis, as well as its radiological severity. Further study indicated that LeY antigen, which was related to the blood group, was associated with primary knee osteoarthritis. Translational potential of this article: This study revealed that blood group AB and LeY antigen was associated with primary knee osteoarthritis, which shed new light on the nature of osteoarthritis, and the development of novel therapy for osteoarthritis. Keywords: Blood group, Kellgren/Lawrence, Knee, LeY antigen, Osteoarthritis

Background Disparities in multiple myeloma (MM) prognosis based on sociodemographic factors may exist. We investigated whether education level at diagnosis influenced Chinese MM patient outcomes. Methods We performed a multicenter retrospective analysis of data from 773 MM patients across 9 centers in China from 2006 to 2019. Sociodemographic and clinical factors at diagnosis and treatment regimens were recorded, and univariate and multivariate analyses were performed. Results Overall, 69.2% of patients had low education levels. Patients with low education levels differed from those with high education levels in that they were more likely to be older, and a higher proportion lived in rural areas, were unemployed, had lower annual incomes and lacked insurance. Additionally, compared to patients with high education levels, patients with low education levels had a higher proportion of international staging system (ISS) stage III classification and elevated lactate dehydrogenase (LDH) levels and underwent transplantation less often. Patients with high education levels had a median progression-free survival (PFS) of 67.50 (95% confidence interval (CI): 51.66–83.39) months, which was better than that of patients with low education levels (30.60 months, 95% CI: 27.38–33.82, p p p p Conclusions Low education levels may independently predict poor survival in MM patients in China.

As tyrosine kinase inhibitors (e.g., Imatinib, IM) fail to induce long-term response in some chronic myeloid leukemia (CML), novel therapies targeting leukemia-dysregulated pathways are necessary. Nuclear-cytoplasmic trafficking of proteins play a key role in the development of leukemia and drug resistance. KPT-330 (Selinexor), an inhibitor of chromosome region maintenance 1 (CRM1, nuclear receptor exportin 1, XPO1), demonstrated activities against a few hematological malignancies. We examined the anti-leukemic efficacy of KPT-330 in IM-resistant CML. Cell viability was examined by MTS assay. Apoptosis and cell cycle were assessed by flow cytometry. CRM1 mRNA was detected by PCR. Expression of CRM1 protein and its cargo proteins were determined by western blot or immunofluorescent staining. Furthermore, we engrafted nude mice subcutaneously with IM-resistant CML K562G. Mice were treated with IM, KPT-330 alone or in combination. Expression of CRM1 in CML were markedly higher than control. KPT-330 inhibited proliferation, induced cell cycle arrest and apoptosis of K562 and K562G. IC50 of IM on K562G was reduced by KPT-330. Mechanistically, KPT-330 inhibited CRM1 and increased the nuclear/cytoplasm ratio of BCR-ABL and P27. p-AKT was downregulated while p-STAT1 and caspase-3 were upregulated. Furthermore, KPT-330 showed anti-leukemic effect in primary IM-resistant CML with T315I mutation in CRM1-dependent manner. In K562G xenograft mice model, KPT-330 inhibited tumor growth and sensitized K562G to IM in vivo. To conclude, KPT-330 showed anti-leukemic activity and sensitized CML to IM in CRM1-dependent manner in vitro and in vivo. KPT-330 represents an alternative therapy for IM-refractory CML, warranting further investigation of CRM1 as therapeutic target.

Artesunate (ART) is a sesquiterpene lactone isolated from the leafy portions of the Chinese herb Artemisia annua. Here, we evaluated the effect of ART on the prostate cancer (PCa) cell lines DU145 and LNCaP and explored its potential mechanisms. ART inhibited the viability and mobility of DU145 and LNCaP cells. Mechanistically, we found that UCA1, one of the most important lncRNAs in malignancies of the urinary system, may be a potential mediator contributing to the tumor suppressor function of ART. First, the UCA1 level was reduced significantly after being exposed to ART. In addition, UCA1 was up-regulated in prostate cancer tissues compared to hyperplastic prostatic tissues, and a higher UCA1 level predicted poor prognosis in PCa patients. Furthermore, reintroduction of UCA1 into PCa cells reversed the effect of ART on apoptosis and metastatic ability. Then we determined that the miR-184/Bcl-2 axis might be the downstream signaling pathway of UCA1 upon ART treatment. UCA1 binds to miR-184 through its seed sequences and may function as a sponge for miR-184.

BACKGROUND Many studies have demonstrated that the long non-coding RNA (lncRNA), NEAT1_1, plays critical roles in various human tumor entities and is related to the survival of patients with malignancies. However, the role of NEAT1_1 in diffuse large B cell lymphoma (DLBCL) remains unclear. The aim of this study was to investigate the role of NEAT1_1 in DLBCL. METHODS The expression of NEAT1_1 was evaluated in paraffin-embedded tissues from 64 DLBCL patients and 15 lymphnoditis patients using the ISH method. The correlations between the expression levels of NEAT1_1 and clinical-pathological features and patients' survival were also analyzed. After knocking down NEAT1_1 using shRNA in the DLBCL cell lines OCI-Ly1 and SUDHL-4, cell viability, apoptosis and migration were assessed by performing CCK8 assays, annexin V-FITC/PI double staining assays and migration filter assays, respectively. RESULTS NEAT1_1 expression was increased in DLBCL tissue compared to lymphnoditis tissue samples (P< 0.001). The NEAT1_1 level was positively related to stage (P= 0.031), IPI (P= 0.017), extranodal site involvement (P= 0.042) and drug response (P= 0.040). Kaplan-Meier analysis showed that high expression levels of NEAT1_1 were correlated with a poor prognosis in DLBCL patients. After shRNA-NEAT1_1 was transfected into OCI-Ly1 and SUDHL-4 for 24 h, the NEAT1_1 level decreased to approximately one-third the level of the control. Moreover, the viability and migration ability of the DLBCL cell lines were significantly suppressed. shRNA-NEAT1_1 induced apoptosis in both DLBCL cell lines. CONCLUSIONS Our results showed that NEAT1_1 plays an oncogenic role in DLBCL. NEAT1_1 expression may serve as a predictive marker for DLBCL patients.

Aberrant activation of the PI3K/Akt/mTOR pathway contributes to the proliferation of malignant cells, and may confer resistance to chemotherapy in various malignancies, including acute myeloid leukemia (AML). Chemoresistance is the major reason for relapse in AML. RAD001 (everolimus) has been used at d1 and d7 of an induction chemotherapy regimen for AML, which has acceptable toxicity and may improve conventional chemotherapeutic treatment. Dual inhibitors of PI3K and mTOR overcome some of the intrinsic disadvantages of rapamycin and its derivatives. In this study, we evaluated the effects of BEZ235, a PI3K/mTOR dual inhibitor, on the multidrug-resistant AML cell lines HL-60/VCR and K562/ADR in vitro. BEZ235 dose-dependently inhibited the viability of HL-60/VCR and K562/ADR cells with the IC50 values of 66.69 and 71.44 nmol/L, respectively. BEZ235 (25-100 nmol/L) dose-dependently inhibited the migration of the two AML cell lines, and it also significantly sensitized the two AML cell lines to VCR and ADR. After treatment with BEZ235, the miR-1-3p levels were markedly increased in HL-60/VCR cells. Using TargetScan analysis and luciferase assays, we showed that miR-1-3p targeted BAG4, EDN1 and ABCB1, the key regulators of cell apoptosis, migration and multidrug resistance, and significantly decreased their levels in the two AML cell lines. Transfection of HL-60/VCR and K562/ADR cells with miR-1-3p-AMO to inhibit miR-1-3p could reverse the anti-proliferation effects of BEZ235. In conclusion, the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1.

To investigate the mechanisms by which berberine suppressed the proliferation of human multiple myeloma cells.Human U266 multiple myeloma cell line was tested. Cell proliferation, apoptosis, ultramicrostructure and secretion function were examined using Cell Counting Kit-8 (CCK8), flow cytometry (FCM), electron and fluorescence microscopy, as well as ELISA assay. The microRNAs (miRs) and transcription factors in U266 cells were detected using arrays and verified by qRT-PCR. EMSA and luciferase assays were used to verify the p65-dependent transactivation of miR-21 gene.Treatment of U266 cells with berberine (40-160 μmol/L) suppressed cell proliferation and IL-6 secretion in dose- and time-dependent manners. Meanwhile, berberine dose-dependently induced ROS generation, G(2)/M phase arrest and apoptosis in U266 cells, and decreased the levels of miR-21 and Bcl-2. Overexpression of miR-21 counteracted berberine-induced suppression of cell proliferation and IL-6 secretion. In U266 cells treated with berberine (80 μmol/L), the activity of NF-κB was decreased by approximately 50%, followed by significant reduction of miR-21 level. berberine (80-160 μmol/L) increased the level of Set9 (lysine methyltransferase) by more than 2-fold, caused methylation of the RelA subunit, which inhibited NF-κB nuclear translocation and miR-21 transcription. In U266 cells treated with berberine (80 μmol/L), knockdown of Set9 with siRNAs significantly increased NF-κB protein level accompanying with a partial recovery of proliferation.In U266 cells, berberine suppresses NF-κB nuclear translocation via Set9-mediated lysine methylation, leads to decrease in the levels miR21 and Bcl-2, which induces ROS generation and apoptosis.

Microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme that specifically catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), has been reported to be over-expressed in a variety of solid tumor cells and tissues, but not in normal tissues. Its association with leukemia, however, has not been fully investigated. Our study revealed, for the first time, that mPGES-1 is over-expressed in human acute myeloid leukemia HL-60 cells. Cytotoxicity assays and flow cytometry showed that MK886, an inhibitor of mPGES-1, inhibits proliferation of HL-60 cells and induces apoptosis in a dose- and time-dependent manner, which may result from down-regulation of mPGES-1 expression and PGE2 synthesis. Evaluation of mediators of apoptotic signaling revealed up-regulation of BAX expression and caspase-3 activity, as well as significant decreases in Bcl2 and P-Akt. We conclude that MK886 reduces the viability of leukemia HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis in a dose-dependent manner, which strongly suggests that mPGES-1 inhibitors should be considered as promising candidates for leukemia treatment.

S-phase kinase-associated protein 2 (SKP2) gene is a tumor suppressor gene, and is involved in the ubiquitinmediated degradation of P27 kip1 .S KP2 and P27 kip1 affect the proceeding and prognosis of leukemia through regulating the proliferation, apoptosis and differentiation of leukemia cells. In this study, we explored the mechanism of reversing of HL-60/A drug resistance through SKP2 down-regulation. HL-60/A cells were nucleofected by Amaxa Nucleofector System with SKP2 siRNA. The gene and protein expression levels of Skp2, P27 kip1 ,a nd multi-drug resistance associated protein (MRP) were determined by reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cell cycle was analyzed by flow cytometry. The 50% inhibitory concentration value was calculated using cytotoxic analysis according to the death rate of these two kinds of cells under different concentrations of chemotherapeutics to compare the sensitivity of the cells. HL-60/A cells showed multi-drug resistance phenotype characteristic by cross-resistance to adriamycin, daunorubicin, and arabinosylcytosine, due to the expression of MRP. We found that the expression of SKP2 was higher in HL-60/A cells than in HL-60 cells, but the expression of P27 kip1 was lower. The expression of SKP2 in HL-60/A cells nucleofected by SKP2 siRNA was down-regulated whereas the protein level of P27 kip1 was up-regulated. Compared with the MRP expression level in the control group (nucleofected by control siRNA), the mRNA and protein expression levels of MRP in HL-60/A cells nucleofected by SKP2 siRNA were lower, and the latter cells were more sensitive to adriamycin, daunorubicin, and arabinosylcytosine. Down-regulating the SKP2 expression and arresting cells in the G0/G1 phase improve drug sensitivity of leukemia cells with down-regulated MRP expression.

Toll-like receptors have been found to be associated with immune-mediated diseases but it is still not clear whether they play a role in immune thrombocytopenic purpura (ITP), especially TLR4. CD4+ T-lymphocyte abnormalities, including Th17, Th1, Th2, and regulator T cell (Treg), are considered important in ITP. There have been few studies regarding the expression of TLR4 and the relationships between TLR4 and Th17 levels in ITP.In this study, we evaluated the expression of TLR4 in monocytes, the plasma concentrations of IL-23, IL-17 and the profiles of Th17, Th1, Th2 cells in 70 patients with ITP and 31 healthy controls. In addition, we evaluated IL-2 and Treg cells in 46 cases of 70 patients with ITP and the same 31 controls.Higher levels of TLR4 expression, higher relative numbers of Th17 and Th1 cells and lower levels of Treg cells were observed in patients when compared with controls (p=0.001 for TLR4; p0.001 for Th17; p=0.014 for Th1; p=0.001 for Treg). The levels of IL-23 and IL-2 were increased (p=0.022 for IL-23; p=0.025 for IL-2), the relative levels of Th2 and concentrations of IL-17 were similar across both groups (p=0.446 for Th2; p=0.316 for IL-17). A significant negative correlation was observed between levels of TLR4 and Treg(r=-0.544, p0.001), but a significantly positive correlation was observed between IL-2 and IL-23 concentration in patients (r=0.441, p=0.004). Neither the correlation between TLR4 and the other CD4(+) T cells and cytokines nor the correlation between the three cytokines and CD4+ T cells was found to be statistically significant.Our data showed that TLR4, CD4+ T cells (Th1, Th17 and Treg cells) and related cytokines (IL-23, IL-2) may take part in the pathogenesis of ITP. TLR4 may play a role through the TLR4-cytokine-CD4+ T lymphocyte cell pathway.

Quercetin is one of the naturally occurring dietary flavonol compounds. It is present abundantly in plants and has chemopreventive and anticancer effects. To investigate its anticancer mechanism, we examined the activity of quercetin against acute leukemia cell line, HL-60. Our results showed that quercetin inhibited cell proliferation and induced apoptosis in a time- and dose-dependent manner. Furthermore, quercetin down-regulated the expression of anti-apoptosis protein Bcl-2 and up-regulated the expression of pro-apoptosis protein Bax. Caspase-3 was also activated by quercetin, which started a caspase-3-depended mitochodrial pathway to induce apoptosis. It was also found that quercetin inhibited the expression of the cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein. Taken together, these findings suggested that quercetin induces apoptosis in a caspase-3-dependent pathway by inhibiting Cox-2 expression and regulates the expression of downstream apoptotic components, including Bcl-2 and Bax. Quercetin can be a potent and promising medicine which might be safely used in leukemia therapy.

Abstract 4749 To compare the cytotoxicity of NK cells on RPMI-8266 multiple myeloma cells before and after thermotherapy, and to explore its mechanism. MethodF RPMI-8226 cell was heated for 2 hours at 42°C and after continous culturing for 48 hours, remove dead cells at lower-speed centrifugation. Detected cytotoxicity of NK cells against RPMI-8226 cells, combinig with or without thermotherapy, by LDH releasing assay at different effect-to-target cell ratios (E:T). Moreover compare the expression of HLA class I molecules and NKG2D ligands-MHC class I chain-related molecule A or B and human cytomegalovirus glycoprotein UL16 binding proteins, ULBPsFULBP1AULBP2AULBP3 on the surface of RPMI 8226 cells were analyzed by flow cytometry. Result As for E:T is 5:1, the cytotoxicity of NK cells combining with or without hyperthermia on the 8266 NK cells are (2.15 ± 0.32)% and (9.32 ± 1.27)% respectively; at E:T(10:1), cytotoxicities are (5.26 ± 0.84 )% and (20.37 ± 1.78)%; at E:T (20:1), they are(7.63 ± 1.05)% and (28.69 ± 2.25)%;at ET(40:1), they are (10. 18 ± 1.53)% and (35.64 ± 4.87)%. At the different target ratio, the cytotoxcity of NK cells combining with or without thermotherapy were significant statistical difference (P 0.05). Conclusion Hyperthermia can enhance cytotoxicity of NK cells on multiple myeloma RPMI-8266 cells through upregulating the expression of NKG2D ligand ULBP1 and ULBP3 molecule on RPMI-8266, while no effect on HLA ± molecules. Disclosures: No relevant conflicts of interest to declare.

4671 Introduction Infection after allo-Stem cell transplantation (SCT) is a major cause for post allo-SCT deaths. The pathogens involved are diverse and sometimes difficult to be distinguished. Treatment is primarily based on clinical history, blood analysis, chest X-ray, computerized tomography (CT) examination and pathogen culture of sputum or bronchoaleolar lavage fluid. Empirical treatment is often used before the results of pathogen culture are available. Here, we reported 2 cases of allo-SCT with similar clinical background but infections due to different pathogens. Clinical information | | Case 1 | Case 2 | |:-------------------------------------- | ------------------------------------------------------ | ------------------------------------ | | Age | 15 | 17 | | Gender | female | male | | Diagnosis | Acute lymphatic leukemia | Acute lymphatic leukemia | | Genetic result | Normal karyotype | Normal karyotype | | Immunological type | Common B cell | T Cell | | Disease state before SCT | Complete remission | Complete remission | | SCT type | Allo- peripheral blood SCT | Allo- peripheral blood SCT | | SCT donor | Older sibling brother | younger sibling sister | | SCT donor age | 18 | 15 | | human leucocyte antigen (HLA) matching | Full match | Full match | | Pretreated regimen before SCT | Classic regimen busulfanum + cyclophosphaminde (Bu/Cy) | Total-body irradiation (TBI) + Bu/Cy | | Neutrophil >1.0×109/L days | +15 days | +21 days | | Platelet >20×109/L days | +19 days | +23 days | | Onset of the lung disease | 45 weeks after SCT | 62 weeks after SCT | | Acute graft-versus-host disease (GVHD) | I∼II | II | | Chronic GVHD | I | I | | Anti-GVHD therapy | Cyclosporine A (CsA) withdrawal 3 months after SCT | CsA withdrawal 4 months after SCT | At the onset of the pulmonary diseases, anti-GVHD drugs (Including prednisone, CsA) were already withdrawn for both cases. There was no GVHD progression after withdrawal of the anti-GVHD drugs. Both cases had fever, ranging from 38 to 39 centigrade. Patients were short of breath. Oxygen inhalation was needed. Case 1 was in severe hypoxia. The oxygen saturation was down to 70%∼80% at the peak severity. Neither of the 2 cases was in need of mechanical ventilation. CT images showed that these 2 cases had similar lung injuries ([Fig 1][1] and [Fig 2][2]). Tissue biopsy revealed that different pathogens were involved in these 2 cases, although they had identical disease history, similar duration after transplantation, same clinical symptoms and signs, even similar CT images. The histological findings of lung biopsies showed that the pathogen for case 1 was aspergillums, whereas that of case 2 was tubercle bacillus. Both cases responded well to the specific treatment, respectively. Patients are now in disease-free state. Conclusions Both tuberculosis and fungus infection could show diffused foci on CT image. The diffused lesions of tuberculosis tend to fuse, whereas little cavities were more frequently seen in fungus infections. After treatment, the lesions of fungus were much easier to be clear than tuberculosis. Diagnostic treatment might be used to distinguish these 2 diseases if biopsy cannot be performed or pathogen culture is negative. ![Fig 1.][3] Fig 1. lung CT of case 1. A: when the pulmonary infection began; B: 2 weeks later; C: 4 weeks later; D: 8 weeks later. ![Fig 2.][3] Fig 2. lung CT of case 1. A: when the pulmonary infection began; B: 2 weeks later; C: 5 weeks later; D: 7 weeks later. Disclosures: No relevant conflicts of interest to declare. [1]: #F1 [2]: #F2 [3]: pending:yes

Background: HLH includes the great majority of patients with macrophage-related disorders. Although HLH is considered as a reactive disease, it is an invariably fatal disease. HLH have 2 types: familial hemophagocytic lymphohistiocytosis and secondary hemophagocytic syndrome. The HLH-2004 protocol made by Histiocytosis Association of America (HAA) was for patients aged 18 years, especially in China. We had 2 HLH cases recently, the 2 patients had different prognosis through different treatment. Patients and treatment: Case 1, a 20 years old man, he had mild infection 3 weeks ago, and was cured by antibiotics. Then 2 weeks ago, he got persistent fever, lymphadenectasis, hepatosplenomegaly and pancytopenia. Bone marrow smear discovered 3.5% hematophagocyte, no malignant cells. His direct bilirubin (DBIL) increased to 229.9μmol/L, fibrinogen decreased to 0.14g/L, albumin decreased to 24.6g/L in 5 days. Then he was treated with the HLH-2004 protocol (VP-16+dexamathsone+ciclosporin A). After 10 days treatment, his DBIL became 149.7μmol/L, fibrinogen increased to 1.73g/L, albumin increased to 31.2g/L, The pancytopenia was improved too. Now he was still in recover state. Case 2, a 33 years old woman, she was diagnosed enteric T-cell Non- Hodgkin’s Lymphoma 3 weeks ago. She had normal blood cell analysis and liver function at that time. She had colon perforation because of the lymphoma before the diagnosis and the abdominal inflammatory was severe. Also 1 week after her diagnosis, she had HLH. We try to improve her state by supportive treatment. No chemotherapy was used. Soon, severe pancytopenia appears, her fibrinogen decreased to 0.84g/L, albumin decreased to 23.1g/L, alanine transarninase (AST) increased to 201U/L. Her state aggravated very fast and died of hemorrhea and shock. Almost all adult patients with HLH had poor prognosis without the HLH-2004 protocol treatment. HLH-2004 protocol might be a hope for adult patients with HLH. We need to investigate the effects of HLH-2004 protocol through treating more adult patients with HLH. Also, after the diagnosis of HLH, the patient should be treated as soon as possible, because the multi-organ failure could be developed very fast. The chance of treatment might be lost because of multi-organ failure.

Background: It had been proved by epidemiology and clinical trials that hypercholesterolemia (HC) and atherosclerosis (AS) had close relations. Lipid could take part in many pathological processes of the AS. Platelets played an important role in this process as an inflammatory mediator. We Chose Platelet aggregation maximum (PAG(M)) and plasma P-selectin as the index of platelet activation, try to explore the transfer of platelet activation and lymphocyte inflammatory reaction in atherosclerosis. Design: We set up the rabbit hyperlipidemia atherosclerosis model through 12 weeks’ hyper lipid feeding. PAG(M), concentrations of plasma P-selectin, Interleukin (IL)- 6, IL-1β, tumor necrosis factor (TNF)-α and mRNA expression of these factors in the lymphocyte were measured at 0 week, 6th week and 12th week time point. Results: At the 6th week time point of the hyper lipid feeding, the rabbit had elevated PAG(M) (68.12%±4.73% vs. 62.67%±3.13%; P=0.002, n=20). The PAG(M) was maintained in the high level at 12th week time point (68.83%±3.35% vs. 62.67%±3.13%; P=0.001, n=20). At the 6th week time point of the hyper lipid feeding, the rabbit had elevated plasma P-selectin, IL-6, IL-1β and TNF-α (6th week vs. 0 week, n=20, P-selectin P=0.005, IL-6 P=0.000, IL-1β P=0.001, TNF-α P=0.001). The expressions of IL-6/mRNA, IL-1β/mRNA and TNF-α/mRNA in lymphocytes were elevated too (6th week vs. 0 week, n=20, IL-6/mRNA P=0.000, IL-1β/mRNA P=0.002, TNF-α/mRNA P=0.000). At the 12th week time point, all of the parameters were maintained in the high level, while there had no significant difference between 12th week time point and 6th week time point. Conclusion: Hyperlipidemia could activate platelet. Increased PAG(M) and plasma P-selectin represented the platelet activation. Hyperlipidemia could induce the production of plasma IL-6, IL-1β and TNF-α. The increased plasma IL-6, IL-1β and TNF-α were partly from the lymphocyte secretion because The IL-1β/mRNA, IL-6/mRNA and TNF-α/mRNA expression of lymphocyte elevated. So in rabbit hyperlipidemia atherosclerosis model, platelet activation and inflammatory factors increasing was the main mechanism, while the lymphocyte took part in the inflammatory process.

Early diagnosis and treatment of patients with sepsis remain a common and severe problem, especially in leukopenic patients.. Toll-like receptor-4 (TLR4) plays a crucial role in immunity as the first defenses system against microbial infection through binding gram-negative bacterial LPS. Blood platelets are not only involved in hemostasis, they also have many features of classic inflammatory cells. The expression of TLR4 on platelet in patients with sepsis, including gram-positive bacteria and gram-negative bacteria, is not known. Studying the differences between them, we investigated whether the expressions of TLR4 on platelet were associated with platelet activation, serum TNF-a and endotoxin levels in patients with sepsis, 8 patients of them with gram-positive bacteria and 15 patients of them with gram-negative bacteria. The number of platelet and function of coagulation were normal before infecting. Comparing with the heath subjects, the expressions of TLR4 and P-selectin on platelets, the levels of serum TNF-a and endotoxin were higher (P

Vascular endothelial growth factor (VEGF), which induces angiogenesis and increases vascular permeability, is a major growth factor mediating tumor progression. In this study, we employed immunohistochemical-staining method to detect the expression of VEGF in lymph nodes taken from39 non-Hodgkin’s lymphomas patients and analyzed the relation of the expression levels to malignant aggressiveness, treatment response, histological grade, clinical stage and prognosis. The patients had been observed for at least 5 years or until death. 9 patients with benign lymphadenopathy were acted as control. The expression of VEGF was assessed according to the percentage of immunoreactive cells in a total of 1000 neoplastic cells (quantitative analysis). Immunoreactivity was graded positive, more than 10% of carcinoma cells stained and negative, no detectable staining or less than 10% of carcinoma cells stained. Furthermore, the qualitative intensity of staining for VEGF was assessed using a scale of 0–3+. The expression analysis of VEGF revealed that in 31 out of 39 (79.49%) specimens VEGF staining was positive. The VEGF staining was always cell membrane. Significant associations were found between the expression of VEGF and histological grade, Ann Arbor stage, prognosis (according to International Prognostic Index, IPI) and chemotherapy response. Among 8 cases of low grade, 7 had lower-level expression and 1 had higher-level expression, but among 31 cases of intermediate and high grade, 13 had lower-level expression and18 had higher-level expression (P=0.044

Multidrug resistance (MDR) was the main cause of treatment failure in leukemic chemotherapy. P170, the protein expressed from MDR-1 gene, play an important role in MDR. P27Kip1 was a member of cyclin dependent kinase inhibitor family. It was also a negative regulator in cell generation cycle. It also promoted cells apoptosis. Valproic acid (VPA) was a kind of histone deacetylace inhibitor which could inhibit cell cycle and induce apoptosis. In the current study, we investigated the effects of VPA on the expression of P27Kip1 and P170 of HL60 cells in vitro. HL60/HT cells were induced from HL60 cells by harringtonine (HT) in gradient concentrations. The P27Kip1 expression and P170 expression were tested in flow cytometry. We tested the expression of P27Kip1 and P170 in normal mononuclear cells, HL60 cells and HL60/HT cells, also the effects of VPA on P27Kip1 expression and P170 expression in HL60 cells and HL60/HT cells. The 50% inhibiting concentration (IC50) of vincristine for HL60/HT cells was 5.2 times higher than that for HL60 cells (0.078ug/ml vs. 0.015ug/ml). The IC50 of HT for HL-60/HT cells was 9.3 times higher than that for HL-60 cells (0.14μg/ml vs. 0.015μg/ml). The IC50 of Cytarabine for HL60/HT cells was 3.65 times higher than that for HL60 cells (0.73ug/ml vs. 0.20ug/ml). The expression of P27Kip1 in normal mononuclear cells was the highest, while that in HL60 cells was higher than HL60/HT cells (96.18±3.13% vs. 85.83±4.65% vs. 35.91±3.13%, one way ANOVA, P0.05). But the P170 expression of HL60/HT cells was 6.71±1.61%, which was much higher than that of normal mononuclear cells or HL60 cells (P0.05). In HL60/HT cells, the expression of P27Kip1 increased after cultured with VPA (66.20±5.07% vs. 35.91±3.13%, P0.05). These results indicate that the P27Kip1 expression in normal mononuclear cells were higher than that in leukemia cells (HL60 cells), and the P27Kip1 expression in common HL60 cells were higher than that in MDR HL60/HT cells. VPA could increase the expression of P27Kip1 in HL60 cells and HL60/HT cells. VPA had no effect on the expression of P170 in HL60 cells or HL60/HT cells. That means, The MDR-reverse effect of VPA may not come from the P170 descent mechanism.

Gestational diabetes mellitus (GDM) was as glucose intolerance of different severity that onset or first recognition during the current pregnancy. GDM was a special complication of pregency and the most common cause of fetal and maternal mortality and morbidity. The etiology of this disease is not clear. Increased platelet function was common in normal pregnancy or type 2 diabetes mellitus (DM) patients in the last decade. However, when pregnancy plus type 2 DM, that is, the GDM, was the platelet function still changed? In the current study, we tested blood platelet function including platelet counts (PC), mean platelet volume (MPV) and granule membrane protein-140 (GMP-140, also known as P-selectin, CD62P) in pregnant women with GDM. CD62P was a sensitive index to evaluate platelet activation. PC and MPV would alter when platelets had been destructed significantly, so they were sensitive indexes for platelet activation too. PC was (206.02±60.23)×109/L in GDM, (228.76±56.24)×109/L in normal pregnancy, (219.76±58.14)×109/L in type 2 DM without pregnancy. MPV was 9.53±1.64fl in GDM, 8.74±1.59fl in normal pregnancy, 9.16±1.23fl in type 2 DM without pregnancy. The PC and MPV had no significant difference among GDM, normal pregnancy and type 2 DM without pregnancy (P>0.05). The expression of CD62P was higher than that of normal pregnancy or type 2 DM (41.82±12.95% vs. 26.21±7.09% or 24.18±8.79% P