Chronic hepatitis C virus (HCV) infection ultimately leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma (HCC). As the standard treatment is not completely efficacious, a safer ...and more effective agent against HCV infection needs to be developed. In this report, we demonstrated that 3‐hydroxy caruilignan C (3‐HCL‐C) isolated from Swietenia macrophylla stems exhibited high anti‐HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC50 value of 10.5 ± 1.2 μm. Combinations of 3‐HCL‐C and interferon‐α (IFN‐α), an HCV NS5B polymerase inhibitor (2′‐C‐methylcytidine; NM‐107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX‐950) increased the suppression of HCV RNA replication. The results suggested that 3‐HCL‐C may be a potential anti‐viral agent. We then demonstrated that 3‐HCL‐C interfered with HCV replication by inducing IFN‐stimulated response element transcription and IFN‐dependent anti‐viral gene expression.
Primary cosmic-ray elemental spectra have been measured with the balloon-borne Cosmic Ray Energetics And Mass (CREAM) experiment since 2004. The third CREAM payload (CREAM-III) flew for 29 days ...during the 2007-2008 Antarctic season. Energies of incident particles above 1 TeV are measured with a calorimeter. Individual elements are clearly separated with a charge resolution of ∼0.12 e (in charge units) and ∼0.14 e for protons and helium nuclei, respectively, using two layers of silicon charge detectors. The measured proton and helium energy spectra at the top of the atmosphere are harder than other existing measurements at a few tens of GeV. The relative abundance of protons to helium nuclei is 9.53 0.03 for the range of 1 TeV/n to 63 TeV/n. This ratio is considerably smaller than other measurements at a few tens of GeV/n. The spectra become softer above ∼20 TeV. However, our statistical uncertainties are large at these energies and more data are needed.
Objectives This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective ...was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. Patients and Methods Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). Results Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score SD = 23.99 30.79) when compared with those who received the aprepitant-based regimen (mean score SD = 3.40 13.18) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). Conclusion The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.
Summary
This study investigated the effects of pre‐procedural anxiety (assessed using the Beck Anxiety Inventory) on sedative requirements in 135 patients undergoing sedation for colonoscopy. Deep ...sedation was defined as loss of consciousness and no response to colonoscopy, and was achieved by target‐controlled infusion of propofol. Patients' characteristics, baseline haemodynamic profiles, Beck Anxiety Inventory scores, effect‐site propofol concentration at loss of consciousness and characteristics of recovery were recorded. No correlations were found between Beck Anxiety Inventory scores and effect‐site propofol concentration at loss of consciousness or baseline haemodynamic profiles. There was no statistical difference in the characteristics of recovery among patients with different levels of anxiety. In conclusion, in patients receiving deep sedation for colonoscopies, the level of pre‐procedural anxiety did not relate to the sedative requirement or post‐procedural recovery characteristics.
We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with ...Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
BACKGROUND: Red blood cell (RBC) alloimmunization is reported to occur at an incidence of 5.2% to 23.5% among patients with thalassemia requiring chronic transfusion. With very limited data on ...alloimmunization among the Chinese population, a territory‐wide study has been performed to look at its prevalence among Chinese thalassemia major patients.
STUDY DESIGN AND METHODS: A retrospective study was conducted by reviewing RBC request records for patients with thalassemia major in Hong Kong from 2006 to 2009. Demographic information and serologic data were retrieved for analysis.
RESULTS: A total of 382 patients were identified and consisted of 190 males and 192 females with a median age of 23 ± 10.4 (range, 0.25 to 52) years. Eighty‐eight patients (23.0%) were reported to have RBC antibodies. Of them, 114 alloantibodies, 18 autoantibodies, and 19 unidentified antibodies were identified. Anti‐E (42, 39.3%), anti‐Mia/Mur (33, 30.85%), anti‐c (14, 13.1%), and anti‐Jka (seven, 6.55%) were the commonest antibodies reported. However, one case of anti‐K (0.9%) and two cases of anti‐Fyb (1.9%) were reported. Seven of the 18 patients with autoantibodies contained a total of 13 alloantibodies. They were anti‐E (five, 38.4%), anti‐Mia/Mur (four, 30.8%), anti‐Jka (two, 15.4%), anti‐c (one, 7.7%), and anti‐Fyb (one, 7.7%).
CONCLUSION: It is the first comprehensive study on Chinese thalassemia major patients. Clinically significant alloantibodies are different from those observed in the Western population, although antibodies developed against Rh antigens are still common. Chinese patients are less likely to have antibodies against Kell and Duffy blood group antigens, but are more prone to develop antibodies against the Miltenberger antigens.
Conducting polymer hydrogels represent a unique class of materials that synergizes the advantageous features of hydrogels and organic conductors and have been used in many applications such as ...bioelectronics and energy storage devices. They are often synthesized by polymerizing conductive polymer monomer within a nonconducting hydrogel matrix, resulting in deterioration of their electrical properties. Here, we report a scalable and versatile synthesis of multifunctional polyaniline (PAni) hydrogel with excellent electronic conductivity and electrochemical properties. With high surface area and three-dimensional porous nanostructures, the PAni hydrogels demonstrated potential as high-performance supercapacitor electrodes with high specific capacitance (∼480 F·g ⁻¹), unprecedented rate capability, and cycling stability (∼83% capacitance retention after 10,000 cycles). The PAni hydrogels can also function as the active component of glucose oxidase sensors with fast response time (∼0.3 s) and superior sensitivity (∼16.7 μA·mM ⁻¹). The scalable synthesis and excellent electrode performance of the PAni hydrogel make it an attractive candidate for bioelectronics and future-generation energy storage electrodes.
Although the contribution of the bone marrow mesenchymal stem cells (BM-MSCs) in cancer progression is emerging, their potential roles in prostate cancer (PCa) remain unclear. Here, we showed that ...PCa cells could recruit BM-MSCs and consequently the metastatic ability of PCa cells was increased. We also found that the increased metastatic ability of PCa cells could be due to the increased PCa stem cell population. Mechanism dissection studies found that the upregulation of Chemokine ligand 5 (CCL5) expression in BM-MSCs and PCa cells, after MSCs infiltrated into the PCa cells, subsequently downregulated androgen receptor (AR) signaling, which was due to inhibition of AR nuclear translocation. Interruption of such signaling led to suppression of the BM-MSCs-induced PCa stem cell population increase and thereby inhibited the metastatic ability of PCa cells. The PCa stem cell increase then led to the upregulation of matrix metalloproteinase 9, ZEB-1, CD133 and CXCR4 molecules, and enhanced the metastatic ability of PCa cells. Therefore, we conclude that the BM-MSCs-mediated increased metastatic ability of PCa cells can be due to the PCa stem cell increase via alteration of the CCL5-AR signaling pathway. Together, these results uncover the important roles of BM-MSCs as key components in the prostate tumor microenvironment to promote PCa metastasis and may provide a new potential target to suppress PCa metastasis by blocking BM-MSCs infiltration into PCa.
A neutral gastric pH is critical for the stability of clots over bleeding arteries. We investigated the effect of preemptive infusion of omeprazole before endoscopy on the need for endoscopic ...therapy.
Consecutive patients admitted with upper gastrointestinal bleeding underwent stabilization and were then randomly assigned to receive either omeprazole or placebo (each as an 80-mg intravenous bolus followed by an 8-mg infusion per hour) before endoscopy the next morning.
Over a 17-month period, 638 patients were enrolled and randomly assigned to omeprazole or placebo (319 in each group). The need for endoscopic treatment was lower in the omeprazole group than in the placebo group (60 of the 314 patients included in the analysis 19.1% vs. 90 of 317 patients 28.4%, P=0.007). There were no significant differences between the omeprazole group and the placebo group in the mean amount of blood transfused (1.54 and 1.88 units, respectively; P=0.12) or the number of patients who had recurrent bleeding (11 and 8, P=0.49), who underwent emergency surgery (3 and 4, P=1.00), or who died within 30 days (8 and 7, P=0.78). The hospital stay was less than 3 days in 60.5% of patients in the omeprazole group, as compared with 49.2% in the placebo group (P=0.005). On endoscopy, fewer patients in the omeprazole group had actively bleeding ulcers (12 of 187, vs. 28 of 190 in the placebo group; P=0.01) and more omeprazole-treated patients had ulcers with clean bases (120 vs. 90, P=0.001).
Infusion of high-dose omeprazole before endoscopy accelerated the resolution of signs of bleeding in ulcers and reduced the need for endoscopic therapy. (ClinicalTrials.gov number, NCT00164866 ClinicalTrials.gov .).
As supply chain risks refer to the risks transmitted among supply chain members and supply chain management (SCM) is concerned with close collaboration among chain members to enhance the chain׳s ...overall performance, we argue that we need to use an SCM perspective in supply chain risk management (SCRM). We identify risk information sharing and risk sharing mechanism as two important joint SCRM practices. Drawing on the literature on agency theory and collaborative relationships, we argue that the effectiveness of these two joint practices in improving financial performance can be strengthened by collaborative relationship characteristics including relationship length, supplier trust, and shared SCRM understanding. We empirically test our conceptual model using the data collected from 350 manufacturing firms in China. The results suggest that both risk information sharing and risk sharing mechanism improve financial performance, and the effectiveness of the former is strengthened by relationship length and supplier trust, while that of the latter is strengthened by shared SCRM understanding. We contribute to research and practice by identifying two useful joint SCRM practices and ascertaining the conditions under which each of the practices is particularly effectively.
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