Background
To test the efficacy of electroacupuncture for patients with refractory functional dyspepsia (FD).
Methods
A 24‐week, 2‐arm, single‐blind, randomized controlled trial was conducted at ...three hospitals in China. Patients with refractory FD were randomly assigned to receive 20 sessions of authentic or sham electroacupuncture in a treatment duration of 4 weeks. The primary outcome was complete absence of dyspeptic symptoms at 16 weeks after initiation of acupuncture (week 16). The secondary outcomes included adequate relief of dyspeptic symptoms, Leeds Dyspepsia Questionnaire (LDQ), Nepean Dyspepsia Index (NDI), and adverse events. Intention‐to‐treat analysis was performed.
Key Results
Two hundred patients were included, of which 196 (98%) completed follow‐up data at week 24. At week 16, 17 (17%) patients in the authentic electroacupuncture group vs 6 (6%) patients in the sham group achieved the primary outcome (P = .014). Sixty‐two (62%) patients had adequate relief in the authentic electroacupuncture group, as compared to 22 (22%) in the sham group (P = .001). The scores of LDQ and NDI were significantly improved in both groups at week 16, and patients in the authentic electroacupuncture group have more improvements (LDQ, mean difference, −2.2, 95% confidence interval, −2.3 to −2.1, P < .001; NDI, −7.3, −10.5 to −4.2, P < .001). Results were similar for all the outcomes assessed at week 24. No serious adverse events were reported in both groups.
Conclusion
Acupuncture efficaciously improves dyspeptic symptoms in patients with refractory FD.
The efficacy of acupuncture in treating refractory functional dyspepsia is unknown. We found that electroacupuncture is efficacious and safe for this population.
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. ...In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33
MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0.01). A positive association was observed between CXCL2 or MIF expression and the number of tumor-infiltrating CD33
MDSCs (P<0.01). Subsequently, we demonstrated that CD45
CD33
CD11b
HLA-DR
MDSCs from fresh BC tissues displayed high levels of suppressive molecules, including Arg1, iNOS, ROS, PDL-1 and P-STAT3, and stronger suppression of T-cell proliferation. Interestingly, these CD45
CD33
CD11b
HLA-DR
MDSCs exhibited increased CXCR2 expression compared with that in peripheral blood from BC patients or healthy controls (P<0.05). Chemotaxis assay revealed that bladder cancer cell line J82 induced MDSC migration via CXCL2/MIF-CXCR2 signaling in vitro. Mechanistic studies demonstrated that J82-induced MDSC trafficking and CXCR2 expression were associated with increased phosphorylation of p38, ERK and p65. Conversely, inhibition of the phosphorylation of p38, ERK or p65 decreased J82-induced MDSC trafficking and CXCR2 expression. CXCL2/MIF-stimulated activation of the mitogen-activated protein kinase and nuclear factor kappa B pathways in MDSCs was MyD88 dependent. Overall, our results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients.
Genetic alterations in the kinase domain of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) patients are associated with sensitivity to treatment with small molecule ...tyrosine kinase inhibitors. Although first-generation reversible, ATP-competitive inhibitors showed encouraging clinical responses in lung adenocarcinoma tumors harboring such EGFR mutations, almost all patients developed resistance to these inhibitors over time. Such resistance to first-generation EGFR inhibitors was frequently linked to an acquired T790M point mutation in the kinase domain of EGFR, or upregulation of signaling pathways downstream of HER3. Overcoming these mechanisms of resistance, as well as primary resistance to reversible EGFR inhibitors driven by a subset of EGFR mutations, will be necessary for development of an effective targeted therapy regimen. Here, we show that BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms. Consistent with this activity, BIBW2992 suppresses transformation in isogenic cell-based assays, inhibits survival of cancer cell lines and induces tumor regression in xenograft and transgenic lung cancer models, with superior activity over erlotinib. These findings encourage further testing of BIBW2992 in lung cancer patients harboring EGFR or HER2 oncogenes.
The limited durability of resin-dentin bonds severely compromises the lifetime of tooth-colored restorations. Bond degradation occurs via hydrolysis of suboptimally polymerized hydrophilic resin ...components and degradation of water-rich, resin-sparse collagen matrices by matrix metalloproteinases (MMPs) and cysteine cathepsins. This review examined data generated over the past three years on five experimental strategies developed by different research groups for extending the longevity of resin-dentin bonds. They include: (1) increasing the degree of conversion and esterase resistance of hydrophilic adhesives; (2) the use of broad-spectrum inhibitors of collagenolytic enzymes, including novel inhibitor functional groups grafted to methacrylate resins monomers to produce anti-MMP adhesives; (3) the use of cross-linking agents for silencing the activities of MMP and cathepsins that irreversibly alter the 3-D structures of their catalytic/allosteric domains; (4) ethanol wet-bonding with hydrophobic resins to completely replace water from the extrafibrillar and intrafibrillar collagen compartments and immobilize the collagenolytic enzymes; and (5) biomimetic remineralization of the water-filled collagen matrix using analogs of matrix proteins to progressively replace water with intrafibrillar and extrafibrillar apatites to exclude exogenous collagenolytic enzymes and fossilize endogenous collagenolytic enzymes. A combination of several of these strategies should result in overcoming the critical barriers to progress currently encountered in dentin bonding.
Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy ...composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes ...an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis. We demonstrate that LDHA is phosphorylated at tyrosine 10 by upstream kinases, HER2 and Src. Targeting HER2 or Src attenuated LDH activity as well as invasive potential in head and neck cancer and breast cancer cells. Inhibition of LDH activity by small hairpin ribonucleic acid or expression of phospho-deficient LDHA Y10F sensitized the cancer cells to anoikis induction and resulted in attenuated cell invasion and elevated reactive oxygen species, whereas such phenotypes were reversed by its product lactate or antioxidant N-acetylcysteine, suggesting that Y10 phosphorylation-mediated LDHA activity promotes cancer cell invasion and anoikis resistance through redox homeostasis. In addition, LDHA knockdown or LDHA Y10F rescue expression in human cancer cells resulted in decreased tumour metastasis in xenograft mice. Furthermore, LDHA phosphorylation at Y10 positively correlated with progression of metastatic breast cancer in clinical patient tumour samples. Our findings demonstrate that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers.
Technologies that use stretchable materials are increasingly important, yet we are unable to control how they stretch with much more sophistication than inflating balloons. Nature, however, ...demonstrates remarkable control of stretchable surfaces; for example, cephalopods can project hierarchical structures from their skin in milliseconds for a wide range of textural camouflage. Inspired by cephalopod muscular morphology, we developed synthetic tissue groupings that allowed programmable transformation of two-dimensional (2D) stretchable surfaces into target 3D shapes. The synthetic tissue groupings consisted of elastomeric membranes embedded with inextensible textile mesh that inflated to within 10% of their target shapes by using a simple fabrication method and modeling approach. These stretchable surfaces transform from flat sheets to 3D textures that imitate natural stone and plant shapes and camouflage into their background environments.
Global satellite observations of temperature and geopotential height (GPH) from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed. The precision, resolution, and accuracy of ...the data produced by the MLS version 2.2 processing algorithms are quantified, and recommendations for data screening are made. Temperature precision is 1 K or better from 316 hPa to 3.16 hPa, degrading to ∼3 K at 0.001 hPa. The vertical resolution is 3 km at 31.6 hPa, degrading to 6 km at 316 hPa and to ∼13 km at 0.001 hPa. Comparisons with analyses (Goddard Earth Observing System version 5.0.1 (GEOS‐5), European Centre for Medium‐range Weather Forecasts (ECMWF), Met Office (MetO)) and other observations (CHAllenging Minisatellite Payload (CHAMP), Atmospheric Infrared Sounder/Advanced Microwave Sounder Unit (AIRS/AMSU), Sounding of the Atmosphere using Broadband Radiometry (SABER), Halogen Occultation Experiment (HALOE), Atmospheric Chemistry Experiment (ACE), radiosondes) indicate that MLS temperature has persistent, pressure‐dependent biases which are between −2.5 K and +1 K between 316 hPa and 10 hPa. The 100‐hPa MLS v2.2 GPH surface has a bias of ∼150 m relative to the GEOS‐5 values. These biases are compared to modeled systematic uncertainties. GPH biases relative to correlative measurements generally increase with height owing to an overall cold bias in MLS temperature relative to correlative temperature measurements in the upper stratosphere and mesosphere.
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