CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
The rotation curve (RC) of the Milky Way out to ~100 kpc has been constructed using ~16,000 primary red clump giants (PRCGs) in the outer disc selected from the LAMOST Spectroscopic Survey of the ...Galactic Anti-centre (LSS-GAC) and the Sloan Digital Sky Survey (SDSS)-III/APOGEE survey, combined with ~5700 halo K giants (HKGs) selected from the SDSS/SEGUE survey. To derive the RC, the PRCG sample of the warm disc population and the HKG sample of halo stellar population are, respectively, analysed using a kinematical model allowing for the asymmetric drift corrections and re-analysed using the spherical Jeans equation along with measurements of the anisotropic parameter beta currently available. The typical uncertainties of RC derived from the PRCG and HKG samples are, respectively, 5-7 km s super( -1) and several tens km s super( -1). We determine a circular velocity at the solar position, ... and an azimuthal peculiar speed of the Sun, ..., both in good agreement with the previous determinations. The newly constructed RC has a generally flat value of 240 km s super( -1) within a Galactocentric distance rof 25 kpc and then decreases steadily to 150 km s super( -1) at r ~ 100 kpc. On top of this overall trend, the RC exhibits two prominent localized dips, one at r ~ 11 kpc and another at r ~ 19 kpc. From the newly constructed RC, combined with other constraints, we have built a parametrized mass model for the Galaxy, yielding a virial mass of the Milky Way's dark matter halo of ... and a local dark matter density, ... (ProQuest: ... denotes formulae/symbols omitted.)
Summary
The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of balloon kyphoplasty (BK), percutaneous vertebroplasty (PVP), and ...non-surgical treatment (NST) for patients with osteoporotic vertebral compression fractures (OVCFs). The results demonstrate that for pain and functional status, PVP was significantly better than NST, while the three treatments did not significantly differ in other outcomes.
Introduction
BK, PVP, and NST are widely used to treat OVCFs, but preferable treatment is unknown. The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of BK, PVP, and NST for patients with OVCFs.
Methods
PubMed, EMBASE, and the Cochrane Library were screened. Based on the preplanned eligibility criteria, we screened and included randomized controlled trials that compared BK, PVP, and NST in treating patients with OVCFs. The risk of bias for individual studies was appraised. The data were pooled using a Bayesian network meta-analysis and a traditional direct comparison meta-analysis.
Results
Of the 1057 relevant studies, 15 were eligible and included. Compared with NST, PVP significantly reduced pain, Oswestry Disability Index (ODI), and Roland–Morris Disability Questionnaire (RMDQ). The comparative efficacy of BK and PVP was similar for pain (mean difference (MD) 0.51, 95% credible interval (CrI) − 0.35 to 1.4), ODI (MD 0.11, 95% CrI − 13 to 13), and RMDQ (MD 1.2, 95% CrI − 2.7 to 5.4). The European Quality of Life–5 Dimensions (EQ–5D) and Physical Component Summary subscales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36 PCS) did not differ significantly. There were also no substantial differences in the risks of subsequent vertebral fractures, adjacent vertebral fractures, and re-fractures at the treated level across all comparators. The results of pairwise meta-analyses were almost consistent with those of network meta-analyses. The treatment ranking indicated that PVP had the highest probability of being the most effective for pain, ODI, RMDQ, and EQ-5D. BK had the highest probability of improving SF-36 PCS and of reducing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST was ranked first in preventing adjacent vertebral fractures.
Conclusion
PVP was the most effective method for improving pain, functional status, and quality of life (based on EQ-5D). BK emerged as the best intervention for decreasing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST could be ranked first in reducing adjacent vertebral fractures. The future directions of OVCFs treatment will depend on the outcomes of additional and larger randomized trials in comparing BK with PVP.
Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
Up-regulation of KCa3.1 by PDGF promotes human BSM cell phenotype modulation through activation of the ERK and AKT signaling pathways.
Airway smooth muscle (ASM) cell phenotype modulation, ...characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to proliferative diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). KCa3.1 has been suggested to be involved in regulating ASM cell activation, proliferation, and migration. However, little is known regarding the exact role of KCa3.1 in ASM cell phenotypic modulation. To elucidate the role of KCa3.1 in regulating ASM cell phenotypic modulation, we investigated the effects of KCa3.1 channels on ASM contractile marker protein expression, proliferation and migration of primary human bronchial smooth muscle (BSM) cells. We found that PDGF increased KCa3.1 channel expression in BSM cells with a concomitant marked decrease in the expression of contractile phenotypic marker proteins including smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (α-SMA), myocardin and KCa1.1. These changes were significantly attenuated by the KCa3.1 blocker, TRAM-34, or gene silencing of KCa3.1. Pharmacological blockade or gene silencing of KCa3.1 also suppressed PDGF-induced human BSM cell migration and proliferation accompanied by a decrease in intracellular free Ca2+ levels as a consequence of membrane depolarization, resulting in a reduction in cyclin D1 level and cell cycle arrest at G0-G1 phase. Additionally, PDGF-induced up-regulation of KCa3.1 and down-regulation of BSM contractile marker proteins were regulated by the ERK inhibitor U0126 and the AKT inhibitor LY294002. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation and provide a potential target for therapeutic intervention for proliferative airway diseases.
A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest ...iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.
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 . . .
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