Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns ...after gefitinib therapy are less well characterized.
Overall, 222 stage N1–N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted.
There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 27.4%), extracranial metastases were most frequent in the VP group (32 of 87 36.8%). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib.
Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1–N2 EGFR-mutant NSCLC but longer duration should be explored.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The coronavirus disease 2019 (COVID-19) pandemic represents a severe global health threat. Selenium (Se), as one of the essential trace elements in human body, is well known for its antioxidant and ...immunity-boosting capabilities that induce a strong antiviral effect. In response to the global pandemic, we highlight here the current status of Se in combating different viruses, as well as the potential application of nano-selenium (nanoSe) in combating COVID-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to ...economize O2 for enhanced PDT against hypoxic tumors. The carrier‐free O2‐economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self‐assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self‐delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier‐free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.
A carrier‐free O2‐economizer (designated as LonCe) is developed based on the metabolic drug Lonidamine (Lon) and photosensitizer chlorin e6 (Ce6), which can interrupt cell metabolism and depress mitochondrial respiration to remit the tumor hypoxia. Experiments show that LonCe will greatly improve the antitumor effect by O2‐economized photodynamic therapy regardless of the hypoxic microenvironment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting ...stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery.
Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days.
Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 1.8% of 857 patients) than in the general anesthesia group (43 5.0% of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 49% vs. 288 33%; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 58% vs. 387 45%; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001).
Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.
The generation of gold carbenes
the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N-O or N-N bonds with alkynes has received considerable attention during recent ...years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N-O or N-N bonds. In this article, we disclose an unprecedented gold-catalyzed formal 3+2 cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds
an α-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air ("open flask").
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IJS, KILJ, NUK, UL, UM, UPUK
Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and ...its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.
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IJS, KILJ, NUK, PNG, UL, UM
Terrestrial ecosystem productivity (TEP) is an important component of ecological services. The variability of the TEP is driven by multiple factors, both natural and anthropogenic. However, little is ...known about the dominant factor driving the TEP change at the pixel level, which may hinder ecosystem management particularly in face of global climate changes. In this study, a 22‐year‐long dataset including climate, net primary production (NPP), and human activity was obtained to identify, at a pixel level, the dominant factors of NPP variation in China from 1992 to 2013. The results showed that: (a) the total NPP of China varied from 3.37 to 4.55 PgC/yr and continued to increase with a larger proportion being contributed from eastern China, (b) radiation is the greatest contributor to the NPP variation in China, followed by temperature and precipitation, (c) human activity‐driven pixels are relatively dispersed, and are mainly located in the rural–urban fringe zones, and (d) a total of five subregions are identified, of which Regions I and II require more attention with regard to future NPP evolution. The results of this study are important at the policy level for future management of China's ecosystems.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interactions and communication, restricted interests and repetitive behaviors. Several ...studies report a high prevalence of gastrointestinal (GI) symptoms in autistic individuals. Cumulative evidence reveals that the gut microbiota and its metabolites (especially short-chain fatty acids, SCFAs) play an important role in GI disorders and the pathogenesis of ASD. However, the composition of the gut microbiota and its association with fecal SCFAs and GI symptoms of autistic children remain largely unknown. In the present study, we sequenced the bacterial 16S rRNA gene, detected fecal SCFAs, assessed GI symptoms and analyzed the relationship between the gut microbiome and fecal SCFAs in autistic and neurotypical individuals. The results showed that the compositions of the gut microbiota and SCFAs were altered in ASD individuals. We found lower levels of fecal acetic acid and butyrate and a higher level of fecal valeric acid in ASD subjects. We identified decreased abundances of key butyrate-producing taxa (Ruminococcaceae, Eubacterium, Lachnospiraceae and Erysipelotrichaceae) and an increased abundance of valeric acid associated bacteria (Acidobacteria) among autistic individuals. Constipation was the only GI disorder in ASD children in the present study. We also found enriched Fusobacterium, Barnesiella, Coprobacter and valeric acid-associated bacteria (Actinomycetaceae) and reduced butyrate-producing taxa in constipated autistic subjects. It is suggested that the gut microbiota contributes to fecal SCFAs and constipation in autism. Modulating the gut microbiota, especially butyrate-producing bacteria, could be a promising strategy in the search for alternatives for the treatment of autism spectrum disorder.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Microplasmas have become an actual topic of interest for research in atomic spectrometric systems. Their excellent characteristics including low power consumption and small size and weight make the ...use of microplasmas a promising technique for developing portable analytical instrumentations for the real-time and on-site measurement of trace species. In this review, the current status of discharge-based microplasmas is presented and discussed from the viewpoint of four typical applications in the field of atomic spectrometry,
i.e.
, excitation source, atomizer, ionization source, and induced vapor generation. Microplasma excitation sources are not only highlighted for the direct detection of trace species by optical emission spectrometry (OES), but also focused on for a series of coupling techniques with gas chromatograph (GC), microelectrodialysis (μED), capillary electrophoresis (CE), chemical vapor generation (CVG), and electrothermal vaporization (ETV). Besides the atomization function, microplasma atomizers could serve as a preconcentration device to achieve the trapping and release of analytes in atomizers. Microplasma ionization sources are used to ablate compounds from sample surfaces for analyte detection and profile analysis. Microplasma-induced vapor generation provides a novel sample introduction approach with the feature of being a green analytical method. The future prospects of microplasma application in the field of atomic spectrometry are also described.
Discharge-based microplasmas for the analysis of trace species by atomic spectrometry are described, with emphasis on four typical applications.
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