Small clinical trials have reported that low-frequency repetitive transcranial magnetic stimulation (rTMS) might improve language recovery in patients with aphasia after stroke. However, no ...systematic reviews or meta-analyses studies have investigated the effect of rTMS on aphasia. The objective of this study was to perform a meta-analysis of studies that explored the effects of low-frequency rTMS on aphasia in stroke patients.
We searched PubMed, CENTRAL, Embase, CINAHL, ScienceDirect, and Journals@Ovid for randomized controlled trials published between January 1965 and October 2013 using the keywords "aphasia OR language disorders OR anomia OR linguistic disorders AND repetitive transcranial magnetic stimulation OR rTMS". We used fixed- and random-effects models to estimate the standardized mean difference (SMD) and a 95% CI for the language outcomes.
Seven eligible studies involving 160 stroke patients were identified in this meta-analysis. A significant effect size of 1.26 was found for the language outcome severity of impairment (95% CI = 0.80 to 1.71) without heterogeneity (I2 = 0%, P = 0.44). Further analyses demonstrated prominent effects for the naming subtest (SMD = 0.52, 95% CI = 0.18 to 0.87), repetition (SMD = 0.54, 95% CI = 0.16 to 0.92), writing (SMD = 0.70, 95% CI = 0.19 to 1.22), and comprehension (the Token test: SMD = 0.58, 95% CI = 0.07 to 1.09) without heterogeneity (I2 = 0%). The SMD of AAT and BDAE comprehension subtests was 0.32 (95% CI = -0.08 to 0.72) with moderate heterogeneity (I2 = 32%,P = 0.22). The effect size did not change significantly even when any one trial was eliminated. None of the patients from the 7 included articles reported adverse effects from rTMS.
Low-frequency rTMS with a 90% resting motor threshold that targets the triangular part of the right inferior frontal gyrus (IFG) has a positive effect on language recovery in patients with aphasia following stroke. Further well-designed studies with larger populations are required to ascertain the long-term effects of rTMS in aphasia treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bright white-light emission was obtained from a novel pyridinium molecule by aggregation. Photophysical, single-crystal structural, and computational studies demonstrated that an additional ...low-energy emission was generated by the excitation of a new intermolecular charge-transfer (CT) band at the ground state that cooperates with the non-quenched high-energy monomer emission to produce white light.
Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A ...disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) forwhole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has ...been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out.
To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism.
LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting.
LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 μM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1β, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment.
The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Solution-based ZnO nanorod arrays (NRAs) were modified with controlled N doping by an advanced ion implantation method, and were subsequently utilized as photoanodes for photoelectrochemical (PEC) ...water splitting under visible light irradiation. A gradient distribution of N dopants along the vertical direction of ZnO nanorods was realized. N doped ZnO NRAs displayed a markedly enhanced visible-light-driven PEC photocurrent density of ~160 μA/cm(2) at 1.1 V vs. saturated calomel electrode (SCE), which was about 2 orders of magnitude higher than pristine ZnO NRAs. The gradiently distributed N dopants not only extended the optical absorption edges to visible light region, but also introduced terraced band structure. As a consequence, N gradient-doped ZnO NRAs can not only utilize the visible light irradiation but also efficiently drive photo-induced electron and hole transfer via the terraced band structure. The superior potential of ion implantation technique for creating gradient dopants distribution in host semiconductors will provide novel insights into doped photoelectrode materials for solar water splitting.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation ...profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96-4.82; P=3.9 × 10(-6)-2.2 × 10(-9)), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual 'stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system.
In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential ...underlying mechanism. Results indicated that Pal exerted inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/mL under neutral environment (pH 7.4), and from 75 to 100 μg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori urease (HPU) and jack bean urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known urease inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against urease inhibition than the competitive Ni2+ binding inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two ureases was reversible, further supporting that sulfhydryl group should be obligatory for urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective inhibitor of H. pylori and its urease targeting the sulfhydryl groups, representing a promising candidate as novel urease inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other urease-related diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sulfate aerosols exert profound impacts on human and ecosystem health, weather, and climate, but their formation mechanism remains uncertain. Atmospheric models consistently underpredict sulfate ...levels under diverse environmental conditions. From atmospheric measurements in two Chinese megacities and complementary laboratory experiments, we show that the aqueous oxidation of SO₂ by NO₂ is key to efficient sulfate formation but is only feasible under two atmospheric conditions: on fine aerosols with high relative humidity and NH₃ neutralization or under cloud conditions. Under polluted environments, this SO₂ oxidation process leads to large sulfate production rates and promotes formation of nitrate and organic matter on aqueous particles, exacerbating severe haze development. Effective haze mitigation is achievable by intervening in the sulfate formation process with enforced NH₃ and NO₂ control measures. In addition to explaining the polluted episodes currently occurring in China and during the 1952 London Fog, this sulfate production mechanism is widespread, and our results suggest a way to tackle this growing problem in China and much of the developing world.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in ...patients with locally advanced resectable oral squamous cell carcinoma (OSCC).
A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety.
Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio HR, 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control.
Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.
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