Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
Summary
Background
Obesity, a comorbid medical condition, is usually observed in patients with established coronary artery disease. Paradoxically, patients with a higher body mass index (BMI) usually ...have better clinical outcomes after coronary revascularization.
Methods
We searched five online databases through December 2017. We identified studies reporting the rate of all‐cause mortality or cardiovascular‐related outcomes among patients after coronary revascularization with percutaneous coronary intervention or coronary artery bypass graft based on various BMI categories. Network meta‐analysis was performed using Bayesian methods.
Results
Sixty‐five records involving 865,774 participants were included in our study. A U‐shaped association was observed across BMI categories for all‐cause mortality. Using normal weight as the reference, all‐cause mortality was increased for (relative risk RR: 2.4; 95% credibility interval CrI: 2.1–2.7) patients with underweight, whereas it was lowered in patients with overweight, obese, and severely obese. This association remained significant in many subgroups. We also observed that the risk of major adverse cardiovascular events (MACE) was lowest among patients with overweight. Furthermore, patients with underweight were associated with greater risks of myocardial infarction (RR: 1.9; 95% CrI: 1.4–2.5), cardiovascular‐related mortality (RR: 2.8; 95% CrI: 1.6–4.7), stroke (RR: 2.0; 95% CrI: 1.3–3.3) and heart failure (RR: 1.7; 95% CrI: 1.1–2.7) compared with normal weight patients; no significant association was observed among individuals with higher BMI.
Conclusions
The ‘obesity paradox’ does exist in patients after coronary revascularization, especially for patients with post‐percutaneous coronary intervention. All‐cause mortality in patients with high BMI is significantly lower compared with patients with normal weight. Furthermore, patients with underweight experience higher rates of cardiovascular outcomes compared with patients with normal weight.
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
MicroRNAs alter multiple cell processes and thus influence tumour carcinogenesis and progression. MiR-100 and miR-99a have been reported to be aberrantly expressed in acute leukaemia. In this study, ...we focused on their functions in acute lymphoblastic leukaemia (ALL) and the molecular networks in which they are involved.
MiR-100 and miR-99a expression levels were measured in acute leukaemia patients by qRT-PCR. Kaplan-Meier analysis and log-rank tests were used to calculate the survival rate. Three human ALL cell lines were studied. Apoptosis and proliferation were analysed using siRNA transfection, western blot and flow cytometry.
In vivo, miR-100 and miR-99a were down-regulated in 111 ALL patients, especially in high-risk groups; their expression levels were correlated with the patient's 5-year survival. In vitro, the restoration of miR-100 and miR-99a in ALL cells suppressed cell proliferation and increased dexamethasone-induced cell apoptosis. Ectopic expression of miR-100 and miR-99a targeted FK506-binding protein 51 (FKBP51) and, in turn, influenced glucocorticoid receptor (GR) activity. Meanwhile, miR-100 and miR-99a overexpression inhibited the expression of IGF1R and mTOR and their downstream oncogene MCL1.
MiR-100 and miR-99a have critical roles in altering cellular processes by targeting both the FKBP51 and IGF1R/mTOR signalling pathways in vitro and might represent a potential novel strategy for ALL treatment.
Rapid economic growth has given rise to a significant increase in ozone precursor emissions in many regions of China, especially in the densely populated North China Plain (NCP) and Yangtze River ...Delta (YRD). Improved understanding of ozone formation in response to different precursor emissions is imperative to address the highly nonlinear ozone problem and to provide a solid scientific basis for efficient ozone abatement in these regions. A comparative study on ozone photochemical production in summer has thus been carried out in the megacities of Tianjin (NCP) and Shanghai (YRD). Two intensive field campaigns were carried out respectively at an urban and a suburban site of Tianjin, in addition to routine monitoring of trace gases in Shanghai, providing data sets of surface ozone and its precursors including nitrogen oxides (NOx) and various non-methane hydrocarbons (NMHCs). Ozone pollution in summer was found to be more severe in the Tianjin region than in the Shanghai region, based on either the frequency or the duration of high ozone events. Such differences might be attributed to the large amount of highly reactive NMHCs in Tianjin. Industry related species like light alkenes were of particular importance in both urban and suburban Tianjin, while in Shanghai aromatics dominated. In general, the ozone problem in Shanghai is on an urban scale. Stringent control policies on local emissions would help reduce the occurrence of high ozone concentrations. By contrast, ozone pollution in Tianjin is probably a regional problem. Combined efforts to reduce ozone precursor emissions on a regional scale must be undertaken to bring the ozone problem under control.
First-principles molecular dynamics simulation reveals the effects of electronic excitation in the amorphization of Ge-Sb-Te. The excitation makes the phase change an element-selective process, ...lowers the critical amorphization temperature considerably, for example, to below 700 K at a 9% excitation, and reduces the atomic diffusion coefficient with respect to that of melt by at least 1 order of magnitude. Noticeably, the resulting structure has fewer wrong bonds and significantly increased phase-change reversibility. Our results point to a new direction in manipulating ultrafast phase-change processes with improved controllability.
Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing ...partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.
This study aimed to explore the treatment effects of various intervention methods on the stress, anxiety, and fatigue of medical workers during the 2019 Coronavirus Disease (COVID-19) pandemic.
We ...conducted computer searches in both Chinese and English databases including China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wang Fang), VIP Chinese Journal Service Platform (VIP), Web of Science, Embase, PubMed, Cochrane Library, Scopus, and ScienceDirect to include prospective randomized controlled studies (Prospective RCT) published before September 30, 2023, regarding different treatment methods for stress, anxiety, and fatigue among healthcare workers during COVID-19. Data on anxiety, stress, and fatigue of research participants were extracted from the included studies, followed by statistical analysis of treatment effects using R software with the meta package.
A total of 9 articles were eventually included, involving a total of 1,466 participants, including 686 in the control group and 780 in the study group. Intervention measures included mindfulness-based therapy in 4 studies and other intervention methods in 5. The anxiety status of the health workers was assessed using the Generalized Anxiety Disorder-7 (GAD-7), and the meta-analysis revealed a pooled mean difference (MD) of -0.53 (95% CI: -1.42, 0.37). Stress status was evaluated by Perceived Stress Scale 4 (PSS-4), and the meta-analysis results showed a post-treatment MD of 0.13 (95% CI: -0.39, 0.65), with a pre- and post-treatment difference MD of -0.44 (95% CI: -2.65, 1.76). Maslach Burnout Inventory (MBI) was employed for the evaluation of fatigue. The meta-analysis results showed an MD of -6.13 (95% CI: -16.68, 4.43) for the MBI Emotional index, an MD of 5.04 (95% CI: -3.25, 13.33) for the Personal Accomplishment index, and an MD of -1.68 (95% CI: -6.50, 3.13) for the Depersonalization index.
Maintaining the mental health of frontline health workers is crucial during the COVID-19 pandemic, and mindfulness-based therapy is the most extensively employed psychological intervention method. However, its effectiveness requires further research confirmation.
Graphene, whose absorbance is approximately independent of wavelength, allows broadband light-matter interactions with ultrafast responses. The interband optical absorption of graphene can be ...saturated readily under strong excitation, thereby enabling scientists to exploit the photonic properties of graphene to realize ultrafast lasers. The evanescent field interaction scheme of the propagating light with graphene covered on a D-shaped fibre or microfibre has been employed extensively because of the nonblocking configuration. Obviously, most of the fibre surface is unused in these techniques. Here, we exploit a graphene-clad microfibre (GCM) saturable absorber in a mode-locked fibre laser for the generation of ultrafast pulses. The proposed all-surface technique can guarantee a higher efficiency of light-graphene interactions than the aforementioned techniques. Our GCM-based saturable absorber can generate ultrafast optical pulses within 1.5 μm. This saturable absorber is compatible with current fibre lasers and has many merits such as low saturation intensities, ultrafast recovery times, and wide wavelength ranges. The proposed saturable absorber will pave the way for graphene-based wideband photonics.
The evolutions of MHD instability behaviors and enhancement of both electrostatic and electromagnetic turbulence towards the plasma disruption have been clearly observed in the HL-2A plasmas. Two ...types of plasma disruptive discharges have been investigated for similar equilibrium parameters: one with a distinct stage of a small central temperature collapse (Formula: see text 5-10%) around 1 millisecond before the thermal quench (TQ), while the other without. For both types, the TQ phase is preceded by a rotating 2/1 tearing mode, and it is the development of the cold bubble from the inner region of the 2/1 island O-point along with its inward convection that causes the massive energy loss. In addition, the micro-scale turbulence, including magnetic fluctuations and density fluctuations, increases before the small collapse, and more significantly towards the TQ. Also, temperature fluctuations measured by electron cyclotron emission imaging enhances dramatically at the reconnection site and expand into the island when approaching the small collapse and TQ, and the expansion is more significant close to the TQ. The observed turbulence enhancement near the X-point cannot be fully interpreted by the linear stability analysis by GENE. Evidences suggest that nonlinear effects, such as the reduction of local Formula: see text shear and turbulence spreading, may play an important role in governing turbulence enhancement and expansion. These results imply that the turbulence and its interaction with the island facilitate the stochasticity of the magnetic flux and formation of the cold bubble, and hence, the plasma disruption.
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