Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Background
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder, in which platelet glycoprotein (GP)IIb–IIIa and GPIb–IX are the two most frequently targeted autoantigens. ...Our previous studies in animal models of ITP demonstrated that intravenous immunoglobulin G (IVIG) could protect against anti‐GPIIb–IIIa autoantibody‐mediated thrombocytopenia but failed to ameliorate ITP induced by most anti‐GPIb–IX autoantibodies.
Objectives
The objective of this human study was to evaluate the association between the specificity of antiplatelet autoantibodies and response to IVIG treatment.
Patients/Methods
In this retrospective study, a cohort of 156 previously untreated adults with severe ITP who underwent IVIG therapy (0.4 g kg−1 day−1 for 5 days) was analyzed. The primary outcome was response defined as platelet counts of ≥ 30 × 109 L−1 and a doubling of baseline counts within 7 days of dosing, and an absence of bleeding.
Results and Conclusions
Among the 66 patients with anti‐GPIb–IX autoantibodies, only 24 (36.4%) achieved a response, as compared with 72 of 90 patients (80.0%) who were negative for anti‐GPIb–IX autoantibodies (relative risk 2.2; 95% confidence interval 1.6–3.1). This study found no difference in response between patients with anti‐GPIIb–IIIa autoantibodies (61.7%) and those without anti‐GPIIb–IIIa autoantibodies (61.3%). Logistic regressions, including main effects and the interaction between these two autoantibodies, showed no influence of anti‐GPIIb–IIIa autoantibodies on the effects of anti‐GPIb–IX autoantibodies with regard to their association with IVIG response. Thus, in adults with ITP, the presence of anti‐GPIb–IX autoantibodies is a predictive factor for poor response to IVIG treatment. Trial registration: ClinicalTrials.gov NCT01666795.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and purpose: The incidence of ischaemic stroke has increased or remained high in China; however, little population‐based evidence is available on the incidence and survival of lacunar ...infarction (LAC). We examined the incidence of LAC in a northern Chinese (Beijing) population and monitored survival.
Methods: A prospective registry population‐based study was conducted over a 6‐year period in a general, unselected, and representative community in Beijing with approximately 100 000 long‐term permanent residents. All first‐ever stroke cases were registered.
Results: A total of 1184 patients with ischaemic stroke were identified; 36.9% (437 cases) were classified as LAC. Age‐standardized incidence rates of LAC ranged from 24.0 to 51.3/100 000 with an average rate of 35.3/100 000 during study period. The incidence of LAC increased with age before 70 years. The incidence of non‐LAC increased with age. There were no significant differences in crude incidence of LAC between men and women (78.4/100 000 vs. 75.4/100 000). The incidence of non‐LAC was significantly higher in men than in women (155/100 000 vs. 107/100 000, P < 0.001). The 28‐day case fatality proportions were significantly lower in patients with LAC (0.5%) versus non‐LAC (14.9%). One year after acute stroke onset, the survival rates between LAC and non‐LAC were similar.
Conclusion: LAC is a common stroke subtype in Northern China. Men or the elderly are more likely to have non‐LAC. Long‐term survival following LAC is similar to non‐LAC patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Here, in an analysis of a 2.92 fb–1 data sample taken at 3.773 GeV with the BESIII detector operated at the BEPCII collider, we measure the absolute decay branching fractions to be B(D0 → K–e+νe) = ...(3.505 ± 0.014 ± 0.033)% and B(D0 → π–e+νe) = (0.295 ± 0.004 ± 0.003)%. From a study of the differential decay rates we obtain the products of hadronic form factor and the magnitude of the CKM matrix element $f$ $^{K}_{+}$(0)|Vcs| = 0.7172 ± 0.0025 ± 0.0035 and $f$ $^{π}_{+}$(0)|Vcd| = 0.1435 ± 0.0018 ± 0.0009.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
The adsorption of 1-naphthylamine, 1-naphthol and phenol on as-prepared and oxidized multiwalled carbon nanotubes (MWCNTs) has been investigated. The results illustrated that both as-prepared and ...oxidized MWCNTs showed high adsorption capacity for the three ionizable aromatic compounds (IACs) studied. Oxidation of MWCNTs increased the surface area and the pore volume, and introduced oxygen-containing functional groups to the surfaces of MWCNTs, which depressed the adsorption of IACs on MWCNTs. Both Langmuir and Freundlich models described the adsorption isotherms very well and the adsorption thermodynamic parameters (Δ
G°, Δ
H° and Δ
S°) were measured. The adsorption for 1-naphthylamine, 1-naphthol and phenol is general spontaneous and thermodynamically favorable. The adsorption of phenol is an exothermic process, whereas the adsorption of 1-naphthylamine and 1-naphthol is an endothermic process. Results of this work are of great significance for the environmental application of MWCNTs for the removal of IACs from large volume of aqueous solutions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. ...Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction.
We present experimental studies on ion acceleration using an 800-nm circularly polarized laser pulse with a peak intensity of 6.9×10^{19} W/cm^{2} interacting with an overdense plasma that is ...produced by a laser prepulse ionizing an initially ultrathin plastic foil. The proton spectra exhibit spectral peaks at energies up to 9 MeV with energy spreads of 30% and fluxes as high as 3×10^{12} protons/MeV/sr. Two-dimensional particle-in-cell simulations reveal that collisionless shocks are efficiently launched by circularly polarized lasers in exploded plasmas, resulting in the acceleration of quasimonoenergetic proton beams. Furthermore, this scheme predicts the generation of quasimonoenergetic proton beams with peak energies of approximately 150 MeV using current laser technology, representing a significant step toward applications such as proton therapy.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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