Patients with N2–3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin–fluorouracil regimen. We aimed to ...compare the efficacy and safety of concurrent adjuvant cisplatin–gemcitabine with cisplatin–fluorouracil in N2–3 nasopharyngeal carcinoma.
We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18–65 years with untreated, non-keratinising, stage T1–4 N2–3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0–1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up.
From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years IQR 36–52; 175 73% male and 65 27% female) were randomly assigned to the cisplatin–fluorouracil group (n=120) or cisplatin–gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32–48). 3-year progression-free survival was 83·9% (95% CI 75·9–89·4; 19 disease progressions and 11 deaths) in the cisplatin–gemcitabine group and 71·5% (62·5–78·7; 34 disease progressions and seven deaths) in the cisplatin–fluorouracil group (stratified hazard ratio 0·54 95% CI 0·32–0·93; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 52% of 117 in the cisplatin–gemcitabine group vs 34 29% of 116 in the cisplatin–fluorouracil group; p=0·00039), neutropenia (37 32% vs 19 16%; p=0·010), and mucositis (27 23% vs 32 28%; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six 5% vs ten 9%). One (1%) patient in the cisplatin–gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin–fluorouracil group had treatment-related deaths.
Our findings suggest that concurrent adjuvant cisplatin–gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2–3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio.
National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.
Fluorinated organic compounds are becoming increasingly important in pharmaceuticals, agrochemicals and materials science. The introduction of trifluoromethoxy groups into new drugs and agrochemicals ...has attracted much attention due to their strongly electron-withdrawing nature and high lipophilicity. However, synthesis of trifluoromethoxylated organic molecules is difficult owing to the decomposition of trifluoromethoxide anion and β-fluoride elimination from transition-metal-trifluoromethoxide complexes, and no catalytic enantioselective trifluoromethoxylation reaction has been reported until now. Here, we present an example of an asymmetric silver-catalysed intermolecular bromotrifluoromethoxylation of alkenes with trifluoromethyl arylsulfonate (TFMS) as a new trifluoromethoxylation reagent. Compared to other trifluoromethoxylation reagents, TFMS is easily prepared and thermally stable with good reactivity. In addition, this reaction is operationally simple, scalable and proceeds under mild reaction conditions. Furthermore, broad scope and good functional group compatibility has been demonstrated by application of the method to the bromotrifluoromethoxylation of double bonds in natural products and natural product derivatives.
Excessive greenhouse gas emissions have led to a series of environmental problems, such as the increasing greenhouse effect, rising sea levels, and melting glaciers at the poles, threatening the ...global environment for human existence. In view of this, the development of CO2 capture technologies with commercialization potential is imperative, as CO2 is the primary contributor to greenhouse gases. In recent years, chemical absorption techniques founded on sterically hindered amines, such as 2-amino-2-methyl-1-propanol (AMP), have garnered escalating interest owing to their benefits of large absorption capacity and diminished energy consumption for regeneration as compared to traditional amine-based methods. In this review, the steric hindrance effect of a sterically hindered amine and its reaction mechanism with CO2 are reviewed. Subsequently, sterically hindered amine absorbents are classified into four kinds, single amine absorbents, blended amine absorbents, biphasic amine absorbents, and nonaqueous amine absorbents, and recent advancements in investigating the kinetic and thermodynamic characteristics of carbon dioxide sequestration through the utilization of sterically hindered amine sorbents are comprehensively evaluated. Technical-economic analysis and life cycle assessment of the CO2 capture processes based on sterically hindered amine absorbents have been comprehensively reviewed. Furthermore, future work for CO2 capture technologies based on sterically hindered amines is suggested.
The protozoan Cryptocaryon irritans is one of the most important ectoparasites of marine fish, causing ‘white spot disease’ and mass mortality in aquaculture. To accurately predict disease outbreaks ...and develop prevention strategies, improved detection methods are required that are sensitive, convenient and rapid. In this study, a pair of specific primers based on the C. irritans 18S rRNA gene was developed and used in a real‐time PCR (qPCR) assay. This assay was able to detect five theronts in 1 L of natural seawater. Furthermore, a linear model was established to analyse the log of Ct value and parasite abundance in seawater (y = –2.9623x + 24.2930), and the coefficient of determination (R2) value was 0.979. A lysis buffer was optimized for theront DNA extraction and used for storage sample. This method was superior to the commercial water DNA kit, and there was no significant degradation of DNA at room temperature for 24–96 hr. A dilution method was developed to manage qPCR inhibitors and used to investigate natural seawater samples in a net cage farm with diseased fish, and the findings were consistent with the actual situation. This study provides a valuable tool for assisting in the early monitoring and control of cryptocaryoniasis in aquaculture.
With the recent advances in tumor treatments,the prognosis of patients with malignancies have been greatly improved.The strategy of surgical treatments for spinal metastases has drawn wide ...attention.Compared with traditional open surgery,minimally invasive spine surgery (MISS) results in similar outcomes,less trauma and more rapid recovery.For patients with spinal metastases,shorter recovery time permits earlier postoperative radiotherapy,achieving better tumor control.This paper discussed the application of MISS in the treatments of spinal metastases in terms of the concept,surgical purpose,indications and surgical options of MISS,hoping to provide reference for clinical practice.
•Practical order rescheduling problem in steel industry is investigated.•A MIP model is proposed considering original, deviation and equilibrium objective.•A discrete differential evolution with new ...mutation and crossover is proposed.•The proposed DDE is compared with 4 standard DE algorithms and the manual method.•Data based system is developed to monitor, diagnose and implement rescheduling.
Order management is a critical and complicated issue in the production process of iron and steel industry, since orders are the bridge between customers and semi-finished/final products in different units. Usually, the scheduling of orders is arranged by skilled planners. However, the initial scheduling may be infeasible during the production process due to the dynamic and frequent variation of production environment. This paper investigates a practical order rescheduling problem to adapt various changes that affect the normal production. The problem is formulated as a mixed integer programming mathematical model considering the original objective, the deviation from the initial scheduling and the equilibrium of production capacity. A discrete differential evolution algorithm with new mutation and crossover operators is proposed to find near-optimal solutions of this problem. Computational experiments are presented on both randomly generated instances and the instances from the practical production. Experimental results illustrate that the proposed algorithm could obtain better solutions compared with four standard differential evolution algorithms and the manual method. Furthermore, a production data based practical decision support system embedding the model and algorithm is developed to monitor the production process, diagnose whether there are high-impact changes of the orders and units, and make rescheduling decisions if necessary.
In this work, (2¯01) oriented β-Ga2O3 thin films have been grown on p-type silicon (100) substrates by laser molecular beam epitaxy. β-Ga2O3/Si p–n heterojunctions are formed as a deep ultraviolet ...(UV) solar-blind photodetector. Those heterojunctions exhibit obvious rectifying characteristics and excellent solar-blind UV photoresponse. The responsivity reaches 370 A/W at 3 V reverse bias under 254 nm UV irradiation. The corresponding external quantum efficiency is over 1.8 × 105%. The combination of wide bandgap semiconductor with silicon might open up possibilities for future generation deep UV solar-blind optoelectronic devices.
•(2¯01) oriented β-Ga2O3 thin films have been grown on p-type silicon substrates by L-MBE.•β-Ga2O3/p-Si heterojunctions exhibit excellent rectifying characteristics.•The responsivity to 254 nm light is higher than as-reported Ga2O3 photodetectors.•β-Ga2O3 can integrate with silicon as a potential solar-blind optoelectronic device.
Chimeric antigen receptor T cell (CAR-T) therapy is novel tumor immunotherapy that enables T cells to specifically recognize tumor-associated antigens through genetic engineering technology, thus ...exerting antitumor effects, and it has achieved encouraging outcomes in leukemia and lymphoma. Building on excellent progress, CAR-T therapy is also expected to work well in solid tumors. Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed at an advanced stage. Current management options for HCC remain limited, and although previous studies have indicated the feasibility of CAR-T cells, ideal therapeutic effects have not yet been achieved. This is, in part, due to the heterogeneity of tumor antigens, high intratumor pressure, immunosuppressive microenvironment, CAR-T cell exhaustion, and serious adverse reactions, which compromise the therapeutic efficiency of CAR-T immunotherapy in HCC. To overcoming these challenges, many ongoing preclinical and clinical studies were conducted. This review summarizes current CAR-T therapy targets in the treatment of HCC, discusses current obstacles and possible solutions in the process, and describes potential strategies to improve the efficacy of CAR-T cells for patients with HCC.
•RM-CN composite was directly prepared via one-step thermal polymerization method.•RM-CN has good catalytic activity under the synergistic effect of adsorption and photocatalysis.•The specific ...surface area of CN has been significantly enhanced with the introduction of RM.•The degradation mechanism of RM-CN was proposed based on capturing experiments and ESR technique.
The red mud/g-C3N4 (RM-CN) composite was directly prepared via one-step thermal polymerization method using melamine and industrial waste residue (red mud) as raw materials. Under the synergistic effect of adsorption and photocatalysis, RM-CN composites have a significant effect for the removal of organic pollutants from wastewater. Compared with pure CN, the specific surface area of RM-CN has been significantly enhanced with the introduction of RM. Additionality, the optical absorption and photocurrent response exhibit obvious enhancement with respect to RM-CN as compared with that of pristine CN photocatalyst. The optimized 0.8% RM-CN product (with the RM mass content of 0.8 wt% in precursor) displayed referable photocatalytic degradation efficiency for antibiotics and dyes under visible light, as well as excellent recycle performance. This work poses a great potential in the actual wastewater treatment, and it is of great significance to the resource utilization and the cost saving of the raw material.
Automatic generation of artistic glyph images is a challenging task that attracts many research interests. Previous methods either are specifically designed for shape synthesis or focus on texture ...transfer. In this paper, we propose a novel model, AGIS-Net, to transfer both shape and texture styles in one-stage with only a few stylized samples. To achieve this goal, we first disentangle the representations for content and style by using two encoders, ensuring the multi-content and multi-style generation. Then we utilize two collaboratively working decoders to generate the glyph shape image and its texture image simultaneously. In addition, we introduce a local texture refinement loss to further improve the quality of the synthesized textures. In this manner, our one-stage model is much more efficient and effective than other multi-stage stacked methods. We also propose a large-scale dataset with Chinese glyph images in various shape and texture styles, rendered from 35 professional-designed artistic fonts with 7,326 characters and 2,460 synthetic artistic fonts with 639 characters, to validate the effectiveness and extendability of our method. Extensive experiments on both English and Chinese artistic glyph image datasets demonstrate the superiority of our model in generating high-quality stylized glyph images against other state-of-the-art methods.
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