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Find video protocols related to scientific articles indexed in Pubmed.
Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: A multicenter, observational study.
Platelets
PUBLISHED: 11-15-2014
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Abstract No effective treatment has been identified for patients of liver cirrhosis (LC) associated with hepatitis B virus (HBV) and severe thrombocytopenia. We aimed to explore the effectiveness and safety of low-dose prednisone or cyclosporine A (CsA) combined with nucleoside analog (NA) in patients with severe thrombocytopenia associated with HBV-related LC. We included 145 consecutive compensated HBV-associated LC patients with severe thrombocytopenia between 1 January 2006 and 31 December 2013. We divided the patients into three groups by treatment strategy, including NA only (n?=?57), NA plus prednisone (n?=?46), and NA plus CsA (n?=?42). We analyzed the platelet counts, bleeding events, liver function, replication of HBV, and outcomes in each group. At all time points during this observation, the platelet counts in prednisone or CsA group were higher than those in the NA only group. There are significant differences in the cumulative rates of bleeding events among the three groups. The platelet counts and treatment were factors associated with bleeding events in multivariate analysis. The differences in HBV-DNA negative rates, HBV-DNA elevated rates, normal serum alanine transaminase rates, serum alanine transaminase elevated more than two times the baseline rates, and HBeAg seropositive conversion ratio among the groups did not reach statistical significance. The adverse events in our study were, in general, mild and balanced among the three treatment groups. Treatment with low-dose prednisone or CsA plus NA could elevate the platelet counts and reduce the risk of bleeding events in HBV LC with severe thrombocytopenia.
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Philadelphia-positive leukemia patients with the Y253H or F359V mutation have a high risk of developing new mutations in the setting of dasatinib resistance.
Leuk. Lymphoma
PUBLISHED: 11-08-2014
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Abstract The treatment outcome and development of new mutations in imatinib- and/or nilotinib-failure Ph+ leukemia patients with highly nilotinib-resistant mutations (Y253H, E255K/V and F359V/C) were assessed on dasatinib. A total of 111 Ph+ leukemia patients were grouped into 3 cohorts by baseline BCR-ABL kinase domain mutation status: no mutation (n=44), non-nilotinib-resistant mutations (n=26), or nilotinib-resistant mutations (n=41). The frequencies of hematological, cytogenetic and molecular responses and clinical resistance to dasatinib were similar among the 3 cohorts during dasatinib therapy. In dasatinib-resistant patients, new mutations were most frequently observed in the cohort with nilotinib-resistant mutations (P=0.001). Multivariate analyses revealed that the advanced disease and harboring the Y253H or F359V mutation before dasatinib were independent predictors of developing new mutations. We concluded that Ph+ leukemia patients with the Y253H or F359V mutation have a high likelihood of developing new mutations in the setting of dasatinib resistance.
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A new phenylpropanoid and a new isoflavone glycoside from Shenqi Fuzheng Injection.
J Asian Nat Prod Res
PUBLISHED: 10-09-2014
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A new phenylpropanoid and a new isoflavone glycoside were isolated from Shenqi Fuzheng Injection. Their structures were elucidated as (?S)-?-ethenyl-4-hydroxy-3-methoxy-benzenemethanol (1) and calycosin 7-O-[?-d-glucopyranosyl (1 ? 4)]-?-d-glucopyranoside (2) by means of spectroscopic methods including UV, IR, HR-ESI-MS, and NMR. The absolute configurations of 1 and 2 were confirmed by quantum chemical calculation and acid hydrolysis.
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Monocytic and Promyelocytic Myeloid-derived suppressor cells may contribute to G-CSF-induced immune tolerance in haplo-identical allogeneic hematopoietic stem cell transplantation.
Am. J. Hematol.
PUBLISHED: 09-23-2014
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We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on monocytic (M), promyelocytic (P)and granulocytic (G) myeloid-derived suppressor cells (MDSCs) both in bone marrow and peripheral blood of 20 healthy donors and the association of MDSCs subgroups with acute and chronic graft-versus-host disease (aGvHD/cGvHD) in 62 patients who underwent haplo-identical allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who received a higher absolute counts of M-MDSCs or P-MDSCs exhibited lower incidence of grade II-IV aGvHD (p=0.001; p=0.031) and extensive cGvHD (p=0.011; p=0.021). In the multivariate analysis, absolute counts of MDSCs in allografts emerged as independent factors that reduced the occurrence of grade II-IV aGvHD (M-MDSCs: HR=0.087, 95% CI=0.020-0.381, p=0.001; P-MDSCs: HR=0.357, 95% CI=0.139-0.922, p=0.033) and extensive cGvHD (M-MDSCs: HR=0.196, 95% CI=0.043-0.894, p=0.035; P-MDSCs: HR=0.257, 95% CI=0.070-0.942, p=0.04). Delayed M-MDSC reconstitution was associated with aGvHD onset. The 3-year cumulative incidence of transplant related mortality and relapse, 3-year probability of disease free survival and overall survival did not differ significantly between these subgroups. Our results suggested that G-CSF-induced immune tolerance may be mediated by M/P-MDSCs in allo-HSCT.
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Triterpenoid saponins from the rhizomes of Anemone flaccida and their inhibitory activities on LPS-induced NO production in macrophage RAW264.7 cells.
J Asian Nat Prod Res
PUBLISHED: 09-19-2014
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A new ursane-type triterpenoid saponin, flaccidoside IV (1), and three new oleanane-type triterpenoid saponins, flaccidosides V-VII (2-4), along with 17 known saponins (5-21), were isolated from the rhizomes of Anemone flaccida. The structures of the new triterpenoid saponins were determined based on spectroscopic analyses and chemical methods. All the isolated saponins were tested for their inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages, and several bisdesmosidic oleanane-type triterpenoid saponins (2, 7, and 10) showed significant inhibitory activities, which indicated they had potential anti-inflammatory activities under their noncytotoxic concentrations in vitro.
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A new lignan from the roots of Syringa pinnatifolia.
Nat. Prod. Res.
PUBLISHED: 09-03-2014
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Phytochemical investigation of the roots of Syringa pinnatifolia has resulted in the isolation of a new lignan, pinnatifolin A (1), together with seven known compounds (2-8). The structures were elucidated on the basis of extensive spectroscopic methods, including NMR, MS, UV and IR spectra. The seven lignans were screened for their antioxidant activity (DPPH assay), and most of them showed potent antioxidant activity.
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Haploidentical stem cell transplantation for the treatment of leukemia: current status.
Expert Rev Hematol
PUBLISHED: 09-02-2014
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Haploidentical stem cell transplantation (haplo-SCT), either with T-cell depletion or T-cell replete, has been a reliable source of stem cells for patients with high-risk leukemia who do not have matched donors because it provides comparable outcomes to human leukocyte antigen-matched sibling donor transplantation, unrelated donor transplantation and umbilical cord blood transplantation. Factors, such as the Hematopoietic Cell Transplantation-Specific Comorbidity Index, associated with transplant outcomes may help us design risk-stratification-directed intervention to improve the prognosis of leukemia patients. Preliminary results of novel protocols, including co-transplant of haploidentical allografts and cord blood, as well as human leukocyte antigen-mismatched stem cell microtransplantation, for leukemia have shown that these approaches are feasible. Several strategies for enhancing the graft-versus-leukemia effects significantly decreased the relapse rate after haplo-SCT. Future direction of research will focus on perfecting available haplo-SCT protocols and determining the optimal time of haplo-SCT for leukemia and 'fit' haploidentical transplant candidates.
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Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG).
J Hematol Oncol
PUBLISHED: 08-21-2014
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Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study.
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Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia: No difference in the high- and low-risk groups.
Int. J. Cancer
PUBLISHED: 08-20-2014
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Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post-consolidation therapy and curative option for adult patients with Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)-haploidentical related donor (haplo-RD) is one of the most important alternative sources for those without HLA-identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in adult Ph-negative ALL CR1 patients (n?=?183). We produced an unmanipulated haplo-HSCT protocol including granulocyte colony stimulating factor (G-CSF) for all donors, intensive immune suppression, anti-thymocyte globulin, and combination of G-CSF-primed bone marrow harvest and G-CSF-mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high-risk versus low-risk groups were 29 versus 23 years. Three-year incidences of relapse mortality and nonrelapse mortality for high-risk versus low-risk groups were 7.1% versus 11.1% (p?=?0.498) and 18.0% versus 16.2% (p?=?0.717), respectively. Three-year probabilities of disease-free survival and overall survival for high-risk versus low-risk groups were 67.6% versus 68.2% (p?=?0.896) and 74.9% versus 72.7% (p?=?0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre-HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high- and low-risk Ph-negative ALL CR1 patients after haplo-HSCT. Haplo-RD could be considered for adults with Ph-negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available.
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Iboga-Type Alkaloids from Ervatamia officinalis.
J. Nat. Prod.
PUBLISHED: 08-06-2014
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Seven new iboga-type alkaloids, ervaoffines A-D (1-4), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1-7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed.
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RUNX1/RUNX1T1-based MRD-monitoring early after allogeneic transplantation rather than c-KIT mutations in adult t(8;21) AML allows further risk stratification.
Blood
PUBLISHED: 08-02-2014
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We asked whether minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels could identify allogeneic hematopoietic stem cell transplanted (allo-HSCT) t(8;21) (q22;q22) AML patients who are at high risk for relapse, together with the impact of c-KIT mutations. Ninety-two consecutive adult t(8;21) patients who received allo-HSCT in complete remission were enrolled. MRD status at 1, 2, 3 months after HSCT identified relapse patients (P=.05, P<.001, P=.0001, respectively). The 2-year cumulative incidence of relapse (CIR) and leukemia free survival (LFS) was 32% vs 9% (P=.01) and 55% vs 70% (P=.12) for patients with and without c-KIT mutations. In multivariate analysis, MRD at the first 3 months after HSCT, rather than c-KIT mutations, was an independent factor for CIR (P=.001) and LFS (P=.001). In addition, 17 patients received donor lymphocyte infusion (DLI) as interventional therapy for MRD and the 2-y CIR and LFS for patients with or without DLI was 24% vs 87% (P=.001) and 64% vs 0% (P<.001), respectively. In conclusion, MRD monitoring early after transplant allows further rapid identification of t(8;21) patients at high risk of relapse and was more predictive of relapse risk than c-KIT mutations.
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[A new chromone glycoside from roots of Polygonum multiflorum].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-22-2014
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Several kinds of column chromatography methods were used to investigate the chemical constituents of roots of Polygonum multiflorum. The structures of the isolated compounds were identified based on their physicochemical properties, spectral data and chemical methods. A new chromone glycoside was isolated and its structure was identified as (S)-2-(2'-hydroxypropyl)-5-methyl7-hydroxychromone-7-0-alpha-L-fucopyranosyl (1-->2)-beta-D-glucopyranoside (1).
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Silica-decorated polypropylene microfiltration membranes with a mussel-inspired intermediate layer for oil-in-water emulsion separation.
ACS Appl Mater Interfaces
PUBLISHED: 07-15-2014
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Silica-decorated polypropylene microfiltration membranes were fabricated via a facile biomimetic silicification process on the polydopamine/polyethylenimine-modified surfaces. The membranes exhibit superhydrophilicity and underwater superoleophobicity derived from the inherent hydrophilicity and the well-defined micronanocomposite structures of the silica-decorated surfaces. They can be applied in varieties of oil-in-water emulsions separation with high permeate flux (above 1200 L/m(2)h under 0.04 MPa) and oil rejection (above 99%). The membranes also have relatively high oil breakthrough pressure reaching 0.16 MPa due to the microporous structure, showing great potential for practical applications. Furthermore, such mussel-inspired intermediate layer provides us a convenient and powerful tool to fabricate organic-inorganic hybrid membranes for advanced applications.
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A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value.
Blood
PUBLISHED: 07-08-2014
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Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients, including those with normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study that identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of well-established markers. We further compared the gene expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and trichloracetic acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (Ara-C), whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML.
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[Chemical constituents of leaves of Psidium guajava].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 06-25-2014
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To study the chemical constituents of the 95% ethanol extract of Psidium guajava. Compounds were separated by using a combination of various chromatographic methods including silica gel, D101 macroporous resin, ODS, Sephadex LH-20 and preparative HPLC. Their structures were elucidated by physicochemical properties and spectral data Eighteen compounds were isolated and identified as (+) -globulol (1), clovane-2beta, 9alpha-diol (2), 2beta-acetoxyclovan-9alpha-ol (3), (+) -caryolane-1 ,9beta-diol (4), ent-T-muurolol (5), clov-2-ene-9alpha-ol (6), isophytol (7), tamarixetin (8), gossypetin (9), quercetin (10), kaempferol (11), guajaverin (12), avicularin (13), chrysin 6-C-glucoside (14), 3'-O-methyl-3, 4-methylenedioxyellagic acid 4'-O-beta-D-glucopyranoside (15), p-hydroxy-benzoic acid (16), guavinoside A (17) and guavinoside B (18). Compounds 2-9 and 14-16 were isolated from this plant for the first time. The ethanol extract showed 61.3% inhibition against the proliferation of colon cancer cell line SW480.
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Securinega alkaloids from the fruits of Flueggea suffruticosa.
J Asian Nat Prod Res
PUBLISHED: 06-24-2014
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Phytochemical investigation on the fruits of Flueggea suffruticosa resulted in the isolation of three new Securinega alkaloids, secu'amamine H (1), 15?-methoxy-14,15-dihydrosecurinine (3), and securinol E (7), as well as eight known ones (2, 4-6, and 8-11). Their structures were elucidated by means of spectroscopic techniques (1D and 2D NMR, MS, UV, and IR). The absolute configurations of the new compounds were established by single-crystal X-ray diffraction and CD analyses.
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Extramedullary Relapse of Acute Leukemia after Haploidentical Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, Treatment, and Clinical Outcomes.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-15-2014
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We examined the incidence, risk factors, treatment, and clinical outcomes of extramedullary relapse (EMR) in 961 acute leukemia patients undergoing HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between 2002 and 2013. Multiple control subjects were selected at random from the same cohort and matched to EMR cases for diagnosis, disease status at HSCT, age at the time of the HSCT, and year of HSCT. Forty patients exhibited EMR, with a median time to EMR of 207 days. The cumulative incidence of EMR was 4.0% at 3 years, and the incidence was higher in acute lymphoblastic leukemia patients compared with acute myeloid leukemia patients (5.6% versus 2.4%). In the multivariate analysis, non-complete remission (CR) status at HSCT (hazard ratio [HR] = 4.6; P = .018) and non-chronic graft-versus-host disease after HSCT (HR = 3.2; P < .001) were the independent risk factors for EMR after haplo-HSCT. Twenty-seven patients received combination treatments, and the proportion of patients who achieved CR was higher than those who received single treatment. Multifocal involvement at EMR (HR = 2.7; P = .024) and non-CR after EMR treatments (HR = 4.6; P < .001) were the independent risk factors for poor survival rates among EMR patients. We found that graft-versus-leukemia effect may help to prevent EMR after haplo-HSCT.
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The cell composition of infused donor lymphocyte has different impact in different types of allogeneic hematopoietic stem cell transplantation.
Clin Transplant
PUBLISHED: 06-11-2014
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Donor lymphocyte infusion (DLI) is often used to enhance the graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we first evaluated the impact of the cell composition of a modified DLI (mDLI) on the prognoses of patients. A total of 194 patients undergoing allo-HSCT were enrolled and received mDLI for various clinical reasons. The infused cellular components of the mDLI were examined by flow cytometry. The results showed that infusion with a lower dose of CD14(+) cells (<0.33 × 10(8) /kg) was an independent risk factor for the occurrence of II-IV acute graft-versus-host disease (aGVHD) (HR = 0.104, p = 0.032) in human leukoctye antigen-identical transplant patients. In addition, a dose of CD14(+) cells greater than the 50th percentile was associated with a lower incidence of hematological relapse and longer disease-free survival (DFS) after the mDLI (relapse: HR = 0.193, p = 0.007; DFS: HR = 0.259, p = 0.016). However, we also found that a greater number of CD14(+) cells were an independent risk factor for II-IV aGVHD (HR = 1.758, p = 0.034) in haploidentical allo-HSCT. In conclusion, our data were the first to demonstrate that the cell composition of a 56 mDLI played a distinct role in different types of allo-HSCT. This finding provided a novel approach for the development of cellular therapies by manipulating the components of infused cells.
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Who is the best donor for a related HLA haplotype-mismatched transplant?
Blood
PUBLISHED: 06-10-2014
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The best donor for a related donor for a human leukocyte antigen (HLA) haplotype-mismatched transplant for hematological neoplasms is controversial. We studied outcomes in 1210 consecutive transplant recipients treated on a uniform protocol. Younger donors and male donors were associated with less nonrelapse mortality (NRM; hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.01-0.39; P = .008 and HR = 0.65; 95% CI = 0.49-0.85; P = .002) and better survival (HR = 0.73; 95% CI = 0.54-0.97; P = .033 and HR = 0.73; 95% CI = 0.59-0.91; P = .005). Father donors were associated with less NRM (HR = 0.65; 95% CI = 0.45-0.95; P = .02), acute graft-versus-host disease (GVHD) (HR = 0.69; 95% CI = 0.55-0.86; P = .001), and better survival (HR = 0.66; 95% CI = 0.50-0.87; P = .003) compared with mother donors. Children donors were associated with less acute GVHD than sibling donors (HR = 0.57; 95% CI = 0.31-0.91; P = .01). Older sister donors were inferior to father donors with regard to NRM (HR = 1.87; 95% CI = 1.10-3.20; P = .02) and survival (HR = 1.59; 95% CI = 1.05-2.40; P = .03). Noninherited maternal antigen-mismatched sibling donors were associated with the lowest incidence of acute GVHD compared with parental donors and noninherited paternal antigen-mismatched sibling donors. Specific HLA disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA haplotype-mismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms.
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[Inhibitory effect of salidroside on hypoxia-induced apoptosis of corpus cavernosum smooth muscle cells in rats].
Zhonghua Nan Ke Xue
PUBLISHED: 05-31-2014
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To investigate the effect of salidroside on hypoxia-induced apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) in rats.
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Preparation of polyphosphazene hydrogels for enzyme immobilization.
Molecules
PUBLISHED: 05-19-2014
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We report on the synthesis and application of a new hydrogel based on a methacrylate substituted polyphosphazene. Through ring-opening polymerization and nucleophilic substitution, poly[bis(methacrylate)phosphazene] (PBMAP) was successfully synthesized from hexachlorocyclotriphosphazene. By adding PBMAP to methacrylic acid solution and then treating with UV light, we could obtain a cross-linked polyphosphazene network, which showed an ultra-high absorbency for distilled water. Lipase from Candida rugosa was used as the model lipase for entrapment immobilization in the hydrogel. The influence of methacrylic acid concentration on immobilization efficiency was studied. Results showed that enzyme loading reached a maximum of 24.02 mg/g with an activity retention of 67.25% when the methacrylic acid concentration was 20% (w/w).
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[Chemical constituents from leaves of Ilex latifolia].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 04-26-2014
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Nine compounds were isolated from the leaves of Ilex latifolia. Their structures were respectively identified as 5-hydroxy-6, 7, 8, 4'-tetramethoxyflavone (1), tangeretin (2), nobiletin (3), 5-hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone (4), 5, 6, 7, 8, 4'-pentamethoxyflavonol (5), 5, 6, 7, 8, 3', 4'-hexamethoxy-flavonol (6), 5-hydroxy-3', 4', 7-trimethoxyflavanone (7), soyacerebroside I (8), and soyacerebroside II (9) by their physicochemical properties and spectroscopic data Compounds 1-9 were isolated from this plant for the first time.
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[Low-dose tadalafil combined with Shuganyiyang capsules for mild-to-moderate erectile dysfunction].
Zhonghua Nan Ke Xue
PUBLISHED: 04-18-2014
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To observe the clinical effect of low-dose once-daily tadalafil combined with Shuganyiyang Capsules in the treatment of mild-to-moderate erectile dysfunction (ED).
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Non-traditional CD4+CD25-CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation.
J Transl Med
PUBLISHED: 04-08-2014
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Non-traditional CD4+CD25-CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT).
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Five new acylphloroglucinol glycosides from the leaves of Eucalyptus robusta.
Nat Prod Commun
PUBLISHED: 04-03-2014
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Five new acylphloroglucinol glycosides, robustasides A-E (1-5), together with a known one (6), were isolated from the leaves of Eucalyptus robusta. The structures were elucidated on the basis of extensive spectroscopic and spectrometric analysis and chemical evidence. The absolute configuration of 1 was further determined by quantum chemical CD calculation.
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New monoterpenoid alkaloids from the aerial parts of Uncaria hirsuta.
Nat. Prod. Res.
PUBLISHED: 04-01-2014
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To investigate the chemical constituents of medicinal plant Uncaria hirsuta, three new monoterpenoid alkaloids, named hirsutanines A-C (1-3), were isolated. Their structures with absolute configurations were elucidated by means of NMR, X-ray diffraction and CD analysis. Compound 3 was the first dimeric monoterpenoid alkaloid obtained from genus Uncaria.
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Association between an impaired bone marrow vascular microenvironment and prolonged isolated thrombocytopenia after allogeneic hematopoietic stem cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-09-2014
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Prolonged isolated thrombocytopenia (PT) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, it remains unclear whether abnormalities of the bone marrow (BM) microenvironment are involved in the pathogenesis of PT. This prospective, nested case-control study included 20 patients with PT, 40 matched patients with good graft function (GGF) after allo-HSCT, and 16 healthy donors (HDs). Cellular elements of the BM microenvironment, including BM endothelial cells (BMECs), perivascular cells, and endosteal cells, were analyzed via flow cytometry and via hematoxylin-eosin and immunohistochemical staining in situ. Moreover, stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) were measured in the plasma of BM via an enzyme-linked immunosorbent assay. No significant differences in endosteal cells (15 per high-power field [hpf] versus 16 per hpf versus 20 per hpf, P > .05) were demonstrated among the patients with PT, GGF, and the HDs. The PT patients exhibited remarkable decreases in cellular elements of the vascular microenvironment, including BMECs (.01% versus .18% versus .20%, P < .0001) and perivascular cells (.01% versus .12% versus .13%, P < .0001), compared with the GGF allo-HSCT recipients and the HDs, respectively. Moreover, significantly lower levels of SDF-1 (3163 pg/mL versus 3928 pg/mL, P = .0002) and VEGF (56 pg/mL versus 123 pg/mL, P < .0001) were found in the BM plasma of the PT patients compared with the BM of the GGF patients. A multivariate analysis revealed that BMECs (odds ratio [OR] = 171.57, P = .002) and cytomegalovirus infection after HSCT (OR = 4.35, P = .009) were independent risk factors for PT. Our data suggested that an impaired BM vascular microenvironment and megakaryocyte-active factors may contribute to the occurrence of PT after HSCT.
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Superior survival of unmanipulated haploidentical hematopoietic stem cell transplantation compared with chemotherapy alone used as post-remission therapy in adults with standard-risk acute lymphoblastic leukemia in first complete remission.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-25-2014
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We wanted to compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with chemotherapy alone in adults with standard-risk acute lymphoblastic leukemia (ALL) in first complete remission (CR1). One hundred thirty-eight consecutive adult patients with standard-risk ALL in CR1 were retrospectively investigated. Of these patients, 59 received chemotherapy alone (group A) and 79 received unmanipulated haploidentical HSCT (group B). Cumulative incidence of relapse at 5 years in group A was significantly higher than that in group B (66.3% versus 29.9%, P < .0001). Overall and disease-free survival in group A were significantly inferior to group B (P < .0001). Moreover, multivariate analyses demonstrated that central nervous system leukemia (P = .002), T cell immunophenotype (P = .044), expression of E2A-PBX1 (P = .007), and positive minimal residual disease after the first cycle of consolidation (P = .004) were correlated with relapse. Patients with 1 of 4 risk factors were assigned to the high-risk group. Otherwise, patients without risk factors were assigned to the low-risk group. In the high-risk group, HSCT had lower relapse rates and superior DFS compared with chemotherapy (P < .05), but in the low-risk group, there were no differences between HSCT and chemotherapy (P > .05). This study is the first to demonstrate that compared with chemotherapy alone, haploidentical HSCT is a better postremission therapy in adults with standard-risk ALL in CR1. Moreover, based on the 4 risk factors, the establishment of risk stratification could identify the subgroup of patients with a higher risk of relapse in adults with standard-risk ALL in CR1. Furthermore, risk stratification-directed postremission therapies using haploidentical HSCT or chemotherapy alone not only reduce relapse rate but also avoid unnecessary treatment-related mortality and improve survival.
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Improving cytomegalovirus-specific T cell reconstitution after haploidentical stem cell transplantation.
J Immunol Res
PUBLISHED: 01-27-2014
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Cytomegalovirus (CMV) infection and delayed immune reconstitution (IR) remain serious obstacles for successful haploidentical stem cell transplantation (haplo-SCT). CMV-specific IR varied according to whether patients received manipulated/unmanipulated grafts or myeloablative/reduced intensity conditioning. CMV infection commonly occurs following impaired IR of T cell and its subsets. Here, we discuss the factors that influence IR based on currently available evidence. Adoptive transfer of donor T cells to improve CMV-specific IR is discussed. One should choose grafts from CMV-positive donors for transplant into CMV-positive recipients (D+/R+) because this will result in better IR than would grafts from CMV-negative donors (D-/R+). Stem cell source and donor age are other important factors. Posttransplant complications, including graft-versus-host disease and CMV infection, as well as their associated treatments, should also be considered. The effects of varying degrees of HLA disparity and conditioning regimens are more controversial. As many of these factors and strategies are considered in the setting of haplo-SCT, it is anticipated that haplo-SCT will continue to advance, further expanding our understanding of IR and CMV infection.
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Clinical profiles of multiple myeloma in Asia-An Asian Myeloma Network study.
Am. J. Hematol.
PUBLISHED: 01-23-2014
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The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However, the differences in clinical characteristics between ethnic groups are not well-defined. In Asian countries, although the incidence of MM has been lower than that of Western countries, there is growing evidence that MM is increasing rapidly. The Asian Myeloma Network decided to initiate the first multinational project to describe the clinical characteristics of MM and the clinical practices in Asia. Data were retrospectively collected from 23 centers in 7 countries and regions. The clinical characteristics at diagnosis, survival rates and initial treatment of 3,405 symptomatic MM patients were described. Median age was 62 years (range, 19-106), with 55.6% of being male. Median overall survival (OS) was 47 months (95% CI 44.0-50.0). Stem cell transplantation was performed in 666 patients who showed better survival rates (79 vs. 41 months, P?
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Isocoumarins from American cockroach (Periplaneta americana) and their cytotoxic activities.
Fitoterapia
PUBLISHED: 01-21-2014
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Four new isocoumarins (1-4), along with three known ones (5-7), were isolated from the 70% ethanol extract of the whole body of the traditional Chinese insect medicine, American cockroach (Periplaneta americana). The structures with absolute configurations of new compounds were elucidated by extensive spectroscopic methods in combination with X-ray diffraction experiment and CD analyses. Compounds 3-5 showed significant cytotoxic activities in HepG2 and MCF-7 cells with IC50 values in the ranges 6.41-23.91 ?M and 6.67-39.07 ?M, respectively.
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Monitoring mixed lineage leukemia expression may help identify patients with mixed lineage leukemia--rearranged acute leukemia who are at high risk of relapse after allogeneic hematopoietic stem cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-16-2014
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To evaluate the prognostic value of the expression of the mixed lineage leukemia (MLL) gene for predicting the relapse of patients with MLL-rearranged acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the levels of MLL transcripts in bone marrow (BM) specimens were monitored serially by real-time quantitative polymerase chain reaction (RQ-PCR) at predetermined time points in 40 patients with MLL-rearranged AL who were treated with allo-HSCT. These patients were followed for a median of 24.5 months (range, 8 to 60 months). A total of 236 BM samples were collected and analyzed. Of these, 230 were monitored concurrently for minimal residual disease (MRD) by flow cytometry (FCM) for leukemia-associated aberrant immune phenotypes and by RQ-PCR for the expression of the Wilms tumor (WT1) gene. The 3-year cumulative incidence of relapse in patients who experienced MLL-positive patients (MLL > .0000%) (n = 9) after HSCT was 93.5% (95% confidence interval [CI], 87% to 100%) compared with 12.5% (95% CI, 5.6% to 19.4%) for MLL-negative patients (n = 31) (P < .001). For these 2 patient groups, the 3-year overall survival (OS) was 12.5% (95% CI, .8% to 24.2%) and 77.8% (95% CI, 68.4% to 87.2%) (P < .001), respectively, and the 3-year leukemia-free survival (LFS) was 0% and 72.2% (95% CI, 61.1% to 83.3%), respectively (P < .001). MLL positivity was associated with a higher rate of relapse (hazard ratio [HR], 18.643; 95% CI, 3.449 to 57.025; P = .001), lower LFS (HR, 7.267; 95% CI, 2.038 to 25.916; P = .002), and lower OS (HR, 8.259; 95% CI, 2.109 to 32.336; P = .002), as determined by Cox multivariate analysis. The expression of the MLL gene had a higher specificity and sensitivity than WT1 or MRD monitored by FCM for predicting the relapse of the patients with MLL + AL. Our results suggest that monitoring the expression of the MLL gene may help to identify patients with MLL + AL who are at high risk of relapse after allo-HSCT and may provide a guide for suitable intervention.
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Polypropylene non-woven meshes with conformal glycosylated layer for lectin affinity adsorption: the effect of side chain length.
Colloids Surf B Biointerfaces
PUBLISHED: 01-09-2014
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The unique characteristics of polypropylene non-woven meshes (PPNWMs), like random network of overlapped fibers, multiple connected pores and overall high porosity, make them high potentials for use as separation or adsorption media. Meanwhile, carbohydrates can specifically recognize certain lectin through multivalent interactions. Therefore glycosylated PPNWMs, combing the merits of both, can be regarded as superior affinity membranes for lectin adsorption and purification. Here, we describe a versatile strategy for the glycosylation of PPNWMs. Two hydrophilic polymers with different side chain length, poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA), were first conformally tethered on the polypropylene fiber surface by a modified plasma pretreatment and benzophenone (BP) entrapment UV irradiation process. Then glucose ligands were bound through the reaction between the hydroxyl group and acetyl glucose. Chemical changes of the PPNWMs surface were monitored by FT-IR/ATR. SEM pictures show that conformal glucose ligands can be achieved through the modified process. After deprotection, the glycosylated PPNWMs became superhydrophilic and had high specific recognition capability toward Concanavalin A (Con A). Static Con A adsorption experiments were further performed and the results indicate that fast adsorption kinetics and high binding capacity can be accomplished at the same time. We also found that increasing the side chain length of polymer brushes had positive effect on protein binding capacity due to improved chain mobility. Model studies suggest a multilayer adsorption behavior of Con A.
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Suffrutines A and B: a pair of Z/E isomeric indolizidine alkaloids from the roots of Flueggea suffruticosa.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-03-2014
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Suffrutines?A (1) and B (2), a pair of novel photochemical Z/E isomeric indolizidine alkaloids, with a unique and highly conjugated C20 skeleton, were isolated from the roots of Flueggea suffruticosa. The structures were elucidated by extensive analysis of NMR spectra and single-crystal X-ray diffraction. The light-induced isomerization and hypothetical biogenetic pathway to 1 and 2, as well as their activity for regulating the morphology of Neuro-2a cells are also discussed.
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Recombinant human thrombopoietin promotes platelet engraftment after haploidentical hematopoietic stem cell transplantation: a prospective randomized controlled trial.
Ann. Hematol.
PUBLISHED: 01-02-2014
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Delayed platelet engraftment (DPE) is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This phenomenon is also a predictor of increased treatment-related mortality and poor survival. Therefore, therapies that promote platelet engraftment to prevent DPE are needed. This prospective randomized controlled trial was designed to investigate whether recombinant human thrombopoietin (rhTPO), administered subcutaneously at a daily dose of 15,000 U from the first day after transplantation, promotes platelet engraftment after haploidentical HSCT. The cumulative incidence of platelet engraftment (platelet recovery to ?20?×?10(9)/L without transfusion support for seven consecutive days) on day 60 post-transplantation was significantly higher in the rhTPO group (n?=?60) than in the control group (n?=?60) (91.7?±?3.8 % vs. 74.5?±?5.8 %, P?=?0.041). Additionally, the number of platelet transfusions from day 14 to day 60 was significantly lower in the rhTPO group than in the control group (4?±?5 vs. 7?±?9 Units, P?=?0.018). No severe adverse effects were observed, with a median follow-up duration of 256 days (range, 48-586 days). The incidences of acute graft-versus-host disease (GVHD), chronic GVHD, and cytomegalovirus viremia and the probabilities of overall survival and disease-free survival did not differ between the two groups. A multivariate analysis of all patients revealed that regardless of assignment to the rhTPO group or the control group (hazard ratio (HR)?=?1.514; 95 % CI (1.024-2.238); P?=?0.038), the number of total infused CD34(+) cells (HR?=?1.304; 95 % CI (1.148-1.482); P?
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[Immunophenotypic characteristics of peripheral blood cells in normal elderly men].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
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This study was aimed to distinguish abnormal cells and to diagnose hematologic diseases through recognizing antigen expression pattern and percentage of peripheral blood cells in normal elderly men. Antigen expression of blast cells, granulocytes, monocytes, lymphocytes, nucleated red blood cells and plasma cells was detected by seven-color flow cytometry in a total of 88 peripheral blood samples from normal elderly men, aged median 82 years old, from 70 to 98 years. Groups were divided according to age, region and underlying diseases, and the percentages of different subgroup cells were examined to confirm whether the differences were significant or not. The results showed that the median proportion of CD34(+) blast cells in peripheral blood from normal elderly men were 0.017% (0.015%-0.020%), with high expression of HLA-DR, CD33, CD13 and CD117, low expression of myeloid antigens, such as CD15, CD11b and CD16, while lymphoid antigens were seldom positive, including CD7, CD19 and CD56. Dim-expression of CD38 was found in peripheral blood blast cells, CD38(dim)+/- cell percentage in blast cells was 61.36% ± 18.26%. In the differentiation and development of granulocytes, CD16(-), CD13(+) CD16(+) (intermediate) and CD16(+) (strong) CD13(+) cells appeared in sequence from immature to mature granulocytes, whose median proportions in nuclear cells were 0.04%, 0.30% and 61.30%, respectively. The percentages of immature monocytes, such as CD64(+) CD14(-) and HLA-DR(+) CD11b(-) cells, were from 0.00% to 0.10% and from 0.07% to 0.68%, separately. No significant differences were found between different subgroups (P > 0.05). It is concluded that the immunophenotypic characteristics and referential percentages of CD34(+) blast cells, granulocytes and monocytes with different development stages in peripheral blood from normal elderly men are recognized, which can help to discriminate abnormal cells.
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[8p11 myeloproliferative syndrome cured by allogeneic hematopoietic stem cell transplantation: two case reports and literature review].
Beijing Da Xue Xue Bao
PUBLISHED: 12-18-2013
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To report 2 rare cases of 8p11 meyloproliferative syndrome cured by allogeneic hematopoietic stem cell transplantation.
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[Clinical characteristics and efficacy analysis for patients over 55 years of age with acute lymphoblastic leukemia].
Beijing Da Xue Xue Bao
PUBLISHED: 12-18-2013
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We investigated the clinical characteristics and therapeutic of elderly patients (?55) with acute lymphoblastic leukemia (ALL).
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[The efficacy and safety of recombinant human granulocyte colony stimulating factor primed donor peripheral cell harvest in treatment of poor graft function after allogeneic stem cell transplantation].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 12-10-2013
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To assess the efficacy and safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) primed donor peripheral blood stem cell (PBSC) on the treatment of poor graft function (PGF) after allogeneic stem cell transplantation(allo-HSCT).
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(+)- and (-)-Cajanusine, a Pair of New Enantiomeric Stilbene Dimers with a New Skeleton from the Leaves of Cajanus cajan.
Org. Lett.
PUBLISHED: 12-02-2013
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A pair of new enantiomeric stilbene dimers, (+)- and (-)-cajanusine [(+)-1 and (-)-1], with a unique coupling pattern were isolated from the leaves of Cajanus cajan . Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic and single-crystal X-ray diffraction analyses, as well as CD calculations. The plausible biogenetic pathway of 1 was also proposed. Additionally, (±)-1, (+)-1, and (-)-1 exhibited inhibitory activities on the growth of human hepatocellular carcinoma cells.
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Monitoring the source of mesenchymal stem cells in patients after transplantation of mismatched-sex hematopoietic stem cells plus third-party cells.
Chin. Med. J.
PUBLISHED: 11-19-2013
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In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in patients with clinically successful engraftments, the source of mesenchymal stem cells (MSCs) remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third-party cells.
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Five new stilbene glycosides from the roots of Polygonum multiflorum.
J Asian Nat Prod Res
PUBLISHED: 11-11-2013
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Five new stilbene glycosides (1-5), together with six known ones, were isolated from the roots of Polygonum multiflorum. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence.
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Triterpenoid saponins from the roots of Clematis uncinata.
Chem. Pharm. Bull.
PUBLISHED: 10-22-2013
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Eight new bisdesmosidic triterpenoid saponins, clematiunicinosides A--H (1--8), along with eleven known ones (9--19), were isolated from the roots of Clematis uncinata. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. All the isolated saponins were tested for their cytotoxic activities on human caski cervical cancer (Caski) cells, and compounds 13, 17 and 19 exhibited inhibitory effect on Caski cells.
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Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial.
J. Clin. Oncol.
PUBLISHED: 10-14-2013
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This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL).
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[Reconstitution kinetics of T helper cells subsets post unmanipulated allogeneic blood and marrow transplantation].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 10-10-2013
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To compare the differences of the T helper cell reconstitution kinetics between HLA matched or HLA mismatched allo-HSCT through exploring the reconstitution kinetics of CD4+ CD25+Foxp3+ cells (CD4+ Treg), CD8+CD25+Foxp3+ cells (CD8+Treg), CD4+CD25-CD127+ conventional T cells (Tcon) and the secretion of IL-17a and IFN-? in CD4+ T cells (Th17 and Th1 cells) or CD8+ T cells (Tc17 and Tc17 cells) post allogeneic hematopoietic stem cells transplantation (allo-HSCT).
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Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-30-2013
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The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 ?g/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2-HG plays in leukemogenesis.
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Chemical constituents from the roots and stems of Erycibe obtusifolia and their in vitro antiviral activity.
Planta Med.
PUBLISHED: 09-30-2013
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Three new quinic acid derivatives, 4-O-caffeoyl-3-O-sinapoylquinic acid methyl ester (1), 5-O-caffeoyl-4-O-syringoylquinic acid methyl ester (2), and 4-O-caffeoyl-3-O-syringoylquinic acid methyl ester (3), as well as four new coumarin glycosides, 7-O-(3-O-sinapoyl-?-D-glucopyranosyl)-6-methoxycoumarin (12), 7-O-(6-O-sinapoyl-?-D-glucopyranosyl)-6-methoxycoumarin (13), 7-O-(2-O-sinapoyl-?-D-glucopyranosyl)-6-methoxycoumarin (14), and 7-O-(6-O-syringoyl-?-D-glucopyranosyl)-6-methoxycoumarin (15), together with eight known compounds (4-11) were isolated from the roots and stems of Erycibe obtusifolia. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. All the compounds were screened for their in vitro antiviral activity against respiratory syncytial virus with a cytopathic effect reduction assay. Among them, the di-O-caffeoyl quinates 8-11 displayed a potent in vitro anti-respiratory syncytial virus effect.
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[Salidroside inhibits hypoxia-induced phenotypic modulation of corpus cavernosum smooth muscle cells in vitro].
Zhonghua Nan Ke Xue
PUBLISHED: 09-10-2013
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To explore the effects of salidroside on the phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMC) in hypoxic SD rats.
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Expression of PML-RAR? is up-regulated during ATRA and arsenics combined induction without influence on long-term prognosis of acute promyelocytic leukemia.
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 09-04-2013
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The early molecular kinetics during all-trans retinoic acid (ATRA) plus arsenic-based induction therapy and its prognostic value for acute promyelocytic leukemia (APL) remain unclear. This study was purposed to investigate the molecular and cytogenetic kinetics and its clinical significance in treatment of APL with ATRA plus arsenic-based induction. The molecular and cytogenetic kinetics was assessed by real-time quantitative RT-PCR and interphase fluorescence in situ hybridization (FISH) in 32 newly diagnosed APL patients. The results showed that the median PML-RAR? transcript levels (PML-RAR?/ABL) were very significantly up-regulated at 14 days of induction therapy compared with that of pre-treatment (40.10% vs 57.74%, P < 0.01), and then decreased at 28 days of induction therapy and at the end of consolidation therapy (6.97% and 0%), respectively. The total of 65.62% and 31.25% patients showed up-regulation of PML-RAR? transcript at 14 and 28 days after induction, as compared with pretreatment. The PML-RAR? copies per APL cell before treatment, and at 14 and 28 days after induction were calculated as 0.9, 2.2, 1.4 by the formula of PML-RARA/ABL(%)×2/APL cells (%). With the median follow-up time of 22 months, 32 patients were still in continuous clinical remission and no molecular relapse occurred. Up-regulation of PML-RARa expression during the induction had no effect on outcomes of APL patients. It is concluded that up-regulation of PML-RARa expression is a common event during induction therapy with ATRA plus arsenics. Up-regulation of PML-RARa expression during induction therapy hasnt influenced the long-term prognosis of APL.
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Mesenchymal Stem Cells versus Mesenchymal Stem Cells Combined with Cord Blood for Engraftment Failure after Autologous Hematopoietic Stem Cell Transplantation: A Pilot Prospective, Open-Label, Randomized Trial.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-29-2013
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Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction.
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Health related quality of life among patients with chronic graft-versus-host disease in China.
Chin. Med. J.
PUBLISHED: 08-29-2013
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Chronic graft-versus-host disease (GVHD), the commonest long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT), has a negative impact on patients health related quality of life (HRQoL). This study was designed to investigate the HRQoL in patients with chronic GVHD in China.
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[Association of the ratio of regulatory and effector T cells with recurrence and chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-28-2013
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To investigate the association of the ratio of regulatory and effector T cells with recurrence and chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
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[The kinetics and prognosis of platelet reconstitution after unmanipulated haploidentical stem cell transplantation without in vitro T cell depletion].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-28-2013
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To explore the kinetics of platelet reconstitution and its prognostic significance in patients received unmanipulated haploidentical stem cell transplantation (Haplo-HSCT) without in vitro T cell depletion.
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[Prevalence of EBV infection in patients with allogeneic hematopoietic stem cell transplantation].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-28-2013
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To analyze the prevalence of Epstein Barr Virus (EBV) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
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[The risk factors and prognosis of transplant-associated thrombotic microangiopathy following acute graft-versus-host disease].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 08-24-2013
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To investigate the risk factors and prognosis of transplant-associated thrombotic microangiopathy (TA-TMA) following acute graft-versus-host disease (aGVHD), and to evaluate the factors that might influence the prognosis of TA-TMA.
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Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study.
Int J Clin Pharmacol Ther
PUBLISHED: 08-22-2013
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Invasive fungal infection (IFI) is common in neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is a broad-spectrum triazole antifungal drug with efficacy in prevention of IFI; however, it has not been previously studied as prophylaxis in a Chinese population.
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Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-07-2013
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Haploidentical hematopoietic stem cell transplantation (HSCT) offers the benefits of rapid and nearly universal donor availability and has been accepted worldwide as an alternative treatment for patients with hematologic malignancies who do not have a completely HLA-matched sibling or who require urgent transplantation. Unfortunately, serious infections and leukemia relapse resulting from slow immune reconstitution remain the 2 most frequent causes of mortality in patients undergoing haploidentical HSCT, particularly in those receiving extensively T cell-depleted megadose CD34(+) allografts. This review summarizes advances in immune recovery after haploidentical HSCT, focusing on the immune subsets likely to have the greatest impact on clinical outcomes. The progress made in accelerating immune reconstitution using different strategies after haploidentical HSCT is also discussed. It is our belief that a predictive immune subset-guided strategy to improve immune recovery might represent a future clinical direction.
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Improved outcomes using G-CSF-mobilized blood and bone marrow grafts as the source of stem cells compared with G-PB after HLA-identical sibling transplantation in patients with acute leukemia.
Clin Transplant
PUBLISHED: 08-01-2013
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This retrospective study compared the transplantation outcomes of 98 consecutive patients with acute leukemia. Allogeneic hematopoietic stem cell transplantation was performed using G-CSF-mobilized bone marrow and blood (G-BM&PB) or G-CSF-mobilized peripheral blood (G-PB) from HLA-identical sibling donors. The G-BM&PB and G-PB groups displayed significantly different neutrophil recovery rates (medians of 15 vs. 14 d, respectively; p = 0.009) but similar platelet recovery rates. The cumulative incidences of grades II-IV acute graft-versus-host disease (aGVHD) in the G-BM&PB and G-PB cohorts were similar (16.2 ± 4.7% vs. 21.8 ± 7.4%, respectively; p = 0.676), but the incidences of grades III-IV aGVHD were significantly different (5.5 ± 3.1% vs. 18.9 ± 7.1%, respectively; p = 0.042). The G-BM&PB and G-PB cohorts displayed similar cumulative incidences of chronic GVHD (cGVHD, 49.1 ± 5.7% vs. 42.7 ± 6.8%, respectively; p = 0.465), one-yr cumulative incidences of treatment-related mortality (16.5 ± 3.5% vs. 24.4 ± 4.1%, respectively; p = 0.220), and five-yr cumulative incidences of relapse (13.9 ± 4.8% vs. 26.8 ± 7.2%, respectively; p = 0.113). The five-yr probability of leukemia-free survival (LFS) was significantly higher in the G-BM&PB group than in the G-PB group (77.8 ± 5.2% vs. 57.6 ± 8.6%, respectively; p = 0.023). Multivariate analysis identified G-PB as an independent risk factor for grades III-IV aGVHD and LFS. Our results suggest that HLA-identical transplantation with G-BM&PB results in superior clinical outcomes compared with G-PB for patients with acute leukemia.
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Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathway.
Leuk. Res.
PUBLISHED: 07-25-2013
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Arsenic trioxide (As2O3) can induce apoptosis in many tumors. However, the associated mechanisms are not clearly understood. We found that As2O3 significantly inhibited the proliferation of WSU-CLL cells and induced apoptosis in dose- and time-dependent manners. WSU-CLL cells treated with 2?M As2O3 showed survivin down-regulation and p53 up-regulation. Survivin siRNA combined with As2O3 further inhibited the proliferation of WSU-CLL cells. p53 inhibition by siRNA prevented the down-regulation of survivin by As2O3 and prevented the As2O3-induced cytotoxicity of WSU-CLL cells. These results suggest that As2O3 may be of therapeutic value for chronic lymphocytic leukemia.
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[The value of the current diagnostic criteria of pulmonary invasive fungal infection after allogeneic hematopoietic stem cell transplantation].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 07-17-2013
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To analyze the practicality of current diagnostic criteria of invasive fungal infection (IFI) in patients with hematologic diseases/malignant tumors, so as to enhance the recognition of characteristics of pulmonary IFI after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
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[Cross-sectional investigation of first-choice of antifungal agents in empirical and preemptive antifungal therapy for patients with hematological malignancies].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 07-06-2013
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To describe the constituent ratio of different kinds of antifungal agents as first choice in empirical or preemptive antifungal therapy for patients with hematological malignancies received chemotherapy or hematopoietic stem cell transplantation (HSCT).
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Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies: a single-institute analysis.
Chin. Med. J.
PUBLISHED: 07-05-2013
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Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival (LFS) and some primary results, such as hematologic recovery, risk of graft-versus-host disease (GVHD), relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source.
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Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation.
Chin. Med. J.
PUBLISHED: 07-05-2013
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The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after allo-HSCT.
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Chemotherapy followed by modified donor lymphocyte infusion as a treatment for relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion: superior outcomes compared with chemotherapy alone and a
Eur. J. Haematol.
PUBLISHED: 07-03-2013
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We retrospectively compared the antileukemic effects of chemotherapy alone and chemotherapy followed by modified donor lymphocyte infusion (DLI) in 82 patients with relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation (HSCT) without in vitro T-cell depletion. We also investigated prognostic factors in patients receiving chemotherapy followed by modified DLI. Thirty-two patients received chemotherapy alone, and the remaining 50 patients received chemotherapy followed by modified DLI. In patients receiving chemotherapy followed by modified DLI, complete remission rate was significantly higher (64.0% vs. 12.5%, P = 0.000), the incidence of relapse was significantly lower (50.0% vs. 100.0%, P = 0.000), and disease-free survival was significantly improved (36.0% vs. 0.0%, P = 0.000) compared with patients receiving chemotherapy alone. Multivariate analysis demonstrated that patients with chronic graft-versus-host disease (GVHD) after intervention (P = 0.000) and patients receiving chemotherapy followed by modified DLI (P = 0.037) were associated with a lower relapse rate. Furthermore, in patients receiving chemotherapy followed by modified DLI, multivariate analysis demonstrated that chronic GVHD after modified DLI (P = 0.039) and duration of minimal residual disease (MRD) (-) ?4 months after modified DLI (P = 0.001) were associated with a lower relapse rate. Our study is the first to suggest that chemotherapy followed by modified DLI is associated with stronger antileukemic effects and better survival in relapsed acute leukemia after haploidentical HSCT without in vitro T-cell depletion. Furthermore, our study suggests that lack of chronic GVHD and duration of MRD (-) <4 months after modified DLI are associated with higher relapse rates in patients receiving chemotherapy followed by modified DLI.
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[Relation of B7-H3 molecule expression in multiple myeloma with poor prognosis and bone destruction].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-03-2013
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This study was purposed to investigate the B7-H3 expression in multiple myeloma cell lines and CD138 cells of patients with multiple myeloma, and explore its clinical significance. Three myeloma cell lines (RPMI8226, U266 and H929) were used. Forty-five patients with multiple myeloma were enrolled in the study. The expression of B7-H3 was detected by flow cytometry and RT-PCR. The relationship between B7-H3 and clinical prognostic factor was analyzed. The results showed that (1)In myeloma cell lines, high expression of B7-H3 was seen in RPMI8226 (92.30 ± 1.1)% and U266 (79.03 ± 1.2)% but not in H929 cell line (4.26 ± 0.2)%. (2) Exogenous IL-6 had no effect on upregulation of B7-H3 in myeloma cell lines. (3) In multiple myeloma patients, the proportions of B7-H3 positive cells in newly diagnosed, remission and relapsed patients were (48.58 ± 33.593)%, (22.16 ± 18.853)%, and (57.65 ± 28.296)%, respectively. The difference between the newly diagnosed and remission patients, and remission and relapsed patients was significant (P = 0.023, P = 0.004). (4)High B7-H3 expression was correlated with high numbers of bone destruction and high levels of serum calcium (P = 0.027, P = 0.046, respectively). It is concluded that the relation of B7-H3 molecule expression with prognosis of multiple myeloma may be negative, but with degree of bone destuction is positive, thus the high expression of B7-H3 may correlated with disease progression and bone destruction of patients with multiple myeloma.
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Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-08-2013
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Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the bone marrow (BM) microenvironment are involved in the pathogenesis of PGF is unclear. In the present prospective nested case-control study, 19 patients with secondary PGF, 38 matched patients with good graft function (GGF) after allo-HSCT, and 15 healthy donors (HDs) were enrolled. The cellular elements of the BM microenvironment, including endosteal cells, perivascular cells, and vascular cells, were analyzed by flow cytometry as well as hematoxylin and eosin and immunohistochemical staining in situ. The median time to occurrence of secondary PGF was 90 days post-transplantation (range, 58 to 264 days). The patients with PGF showed markedly hypocellular marrow (10% versus 45% versus 45%; P < .0001) with scattered hematopoietic cells and significantly lower CD34(+) cells (0.07% versus 0.26% versus 0.26%; P < .0001), endosteal cells (4 per high-power field [hpf] versus 16 per hpf versus 20 per hpf; P < .001), perivascular cells (0.008% versus 0.10% versus 0.12%; P < .0001), and endothelial progenitor cells (0.008% versus 0.16% versus 0.18%; P < .0001) compared with GGF allo-HSCT recipients and HDs, respectively. Multivariate analyses revealed that endothelial progenitor cells (odds ratio, 150.72; P = .001) and the underlying disease (odds ratio, 18.52; P = .007) were independent risk factors for secondary PGF. Our results suggest that the impaired BM microenvironment may contribute to the occurrence of secondary PGF post-HSCT.
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The effect of anti-TGF-?2 antibody functionalized intraocular lens on lens epithelial cell migration and epithelial-mesenchymal transition.
Colloids Surf B Biointerfaces
PUBLISHED: 06-07-2013
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Migration and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) are main causes of central posterior capsule opacification after cataract extraction combined with intraocular lens (IOL) implantation. In this study, commercially available hydrophobic acrylic IOLs were first pretreated with atmospheric pressure glow discharge plasma to produce plenty of negatively charged chemical groups onto IOL surface, then polyethylenimine was deposited onto IOL surfaces as a precursor monolayer, and then anti-TGF-?2 (anti-T) antibody and poly-l-lysine were sequentially deposited onto IOL surface for four cycles followed by another upmost monolayer of anti-T antibody via layer-by-layer self-assembly technique. After the fabrication of anti-T antibody multilayers on IOL surface, the surface characteristics of the anti-T antibody functionalized IOL, as well as its effect on LECs adhesion, proliferation, migration and EMT were then tested in this study. Our results revealed that anti-T antibody multilayers could be successfully immobilized onto IOL surfaces by plasma pretreatment and layer-by-layer self-assembly technique, and could keep stable for at least 3 months on IOL surface. The anti-T antibody immobilized in the multilayers on IOL surfaces showed good immunological activity by its specific antigen-antibody interaction with exogenous TGF-?2. Anti-T antibody functionalized IOL surface was as smooth and flat as the untreated IOL surface. No difference in optical or physical properties was found between the anti-T antibody functionalized IOLs and the untreated IOLs. Compared with the untreated IOLs, the anti-T antibody functionalized IOL greatly inhibited LECs from migration and EMT, yet showed only transient inhibition to LECs adhesion and no inhibition to LECs proliferation. With these data, we demonstrate a simple, inexpensive, and feasible method to fabricate surface functionalized IOL for in situ capture and neutralization of TGF-?2 in the capsular bag, which might be a possible solution to preventing posterior capsule opacification after cataract surgery.
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Substitution of cyclophosphamide in the modified BuCy regimen with fludarabine is associated with increased incidence of severe pneumonia: a prospective, randomized study.
Int. J. Hematol.
PUBLISHED: 05-05-2013
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The modified busulfan-cyclophosphamide (mBuCy) regimen, combined with hydroxyurea, cytarabine and semustine, is the most frequently used myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation in our unit. It is unknown, however, whether fludarabine can be substituted for cyclophosphamide in the mBuCy regimen. We carried out a prospective study to compare modified busulfan-fludarabine (mBuF) with mBuCy, aiming to reduce the treatment-related mortality, with non-inferiority of other outcomes. The mBuCy regimen consisted of hydroxyurea 80 mg/kg on day -10; cytarabine 2 g/m(2) on day -9; busulfan 9.6 mg/kg, intravenously on day -8 through -6; and cyclophosphamide 3.6 g/m(2) on day -5 and -4 and semustine 250 mg/m(2) on day -3. In the mBuF regimen, cyclophosphamide was substituted with fludarabine 30 mg/m(2) through day -5 to -1. Mobilized blood and marrow stem cells were collected from HLA-matched siblings. The trial was suspended due to a tendency of higher incidence of severe pneumonia in the mBuF arm, in which 105 patients were enrolled. After follow-up for another 22 months, a significantly increased incidence of severe pneumonia (31.1 %) was observed in the mBuF arm (11.6 % in mBuCy). This finding suggests that it is uncertain whether it is appropriate to substitute fludarabine for cyclophosphamide under any drug combination. This study was registered at www.chictr.org/cn under identifier ChiCTR-TRC-09000470.
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Immobilization of sodium alginate sulfates on polysulfone ultrafiltration membranes for selective adsorption of low-density lipoprotein.
Acta Biomater
PUBLISHED: 04-26-2013
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A novel method for the immobilization of sodium alginate sulfates (SAS) on polysulfone (PSu) ultrafiltration membranes to achieve selective adsorption of low-density lipoprotein (LDL) was developed, which involved the photoinduced graft polymerization of acrylamide on the membrane and the Hofmann rearrangement reaction of grafted acrylamide followed by chemical binding of SAS with glutaraldehyde. The surface modification processes were confirmed by attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy characterization. Zeta potential and water contact angle measurements were performed to investigate the surface charge and wettability of the membranes. An enzyme-linked immunosorbent assay was used to measure the binding of LDL on plain and modified PSu membranes. It was found that the PSu membrane immobilized with sodium alginate sulfates (PSu-SAS) greatly enhanced the selective adsorption of LDL from protein solutions and the absorbed LDL could be easily eluted with sodium chloride solution, indicating a specific and reversible binding of LDL to SAS, mainly driven by electrostatic forces. Furthermore, the PSu-SAS membrane showed good blood compatibility as examined by platelet adhesion. The results suggest that the PSu-SAS membranes are promising for application in simultaneous hemodialysis and LDL apheresis therapy.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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