Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
This paper reports the effects of fiber breakage defects and waviness defects on the compressive fatigue behavior and the progressive damage evolution process of 3D Multiaxial Braided Composites (3DMBCs). Combined wit...This paper reports the effects of fiber breakage defects and waviness defects on the compressive fatigue behavior and the progressive damage evolution process of 3D Multiaxial Braided Composites (3DMBCs). Combined with finite element compression simulation and ultra-depth microscope, the internal defect content of composites with different braiding angles was determined. The results demonstrate that the weakening effect of waviness and fiber breakage defects is greater than the strengthening effect of the braiding angle. This causes the fatigue resistance of 3DMBCs with the 31° braiding angle being better in both directions of 0° and 90°. The increase of 4° waviness and 10% fiber breakage defect results in the average fatigue life of composites being shortened by 48% and the energy consumption rate increased by 10% at 85% stress level in 90° compression direction. The alteration in loading direction modifies the included angle corresponding to the stress component. The stress component parallel to the fiber direction under compressive fatigue load leads to interfacial debonding in the composites, whereas the stress component perpendicular to the fiber direction results in pronounced shear failure.展开更多
Halogenated aromatic disinfection byproducts(DBPs)are gradually receiving attention due to their high detection frequency and usually higher toxicity than regulated DBPs.In this study,we established a solid phase extr...Halogenated aromatic disinfection byproducts(DBPs)are gradually receiving attention due to their high detection frequency and usually higher toxicity than regulated DBPs.In this study,we established a solid phase extraction(SPE)-LC-MS/MS method to simultaneously trace analyze 59 halogenated aromatic DBPs.The limits of detection and limits of quantification of halogenated aromatic DBPs ranged from 0.03 to 135.23 ng/L and from 0.1 to 450.76 ng/L,respectively.The range of recoveries and relative standard deviation(RSD)in river water were between 72.41%to 119.54%and 1.86%to 16.03%,respectively.Therefore,this method can be used to accurately analyze trace levels of halogenated aromatic DBPs in drinking water.The occurrence and transformation of halogenated aromatic DBPs were explored based on this method.In the chlorinated simulated source water and chlorinated river water,20 and 45 halogenated aromatic DBPs were determined,respectively.The active halogen species(HOCl,HOBr,and HOI)first reacted with natural organic matter(NOM)to form halogenated aromatic DBPs.Then,chlorine further reacted with the halogenated aromatic DBPs to convert them into small-molecule halogenated aliphatic DBPs through oxidation,electrophilic substitution,and hydrolysis reaction,etc.In the chlorinated simulated source water,chlorinated river water,and tap water,the toxicity contribution of bromoacetic acids(Br-HAAs)accounted for themajority(>71.16%).Given that halogenated aromatic DBPs are intermediate products of halogenated aliphatic DBPs,controlling the formation of halogenated aromatic DBPs is beneficial in decreasing the formation of halogenated aliphatic DBPs,thereby diminishing the toxicity of drinking water.展开更多
With the global advancement of the circular economy,integrating reverse osmosis(RO)or forward osmosis(FO)with anaerobic membrane bioreactor(AnMBR)offers a promising approach to simultaneously generate high-grade recla...With the global advancement of the circular economy,integrating reverse osmosis(RO)or forward osmosis(FO)with anaerobic membrane bioreactor(AnMBR)offers a promising approach to simultaneously generate high-grade reclaimed water,produce energy,and preserve valuable nutrients from municipal wastewater.However,the selectivity of these osmotic membranes towards ammonia nitrogen,a major component in municipal wastewater and anaerobic effluent,remains unsatisfactory due to its similar polarity and hydraulic radius to water molecules.Therefore,enhancing the ammonia nitrogen rejection of osmotic membranes is imperative to maximize the quality of reclaimed water and minimize the loss of ammonia nitrogen resources.Unfortunately,the current understanding of the mapping relationship between ammonia nitrogen transmembrane diffusion and the micro/nano-structure of osmotic membranes is not systematic,making precise optimization of the membranes challenging.Hence,this review comprehensively analyzed the diffusion behavior of ammonia nitrogen through osmotic membranes to lay the foundation for targeted regulation of membrane fine structure.Initially,the desire for ammonia/ammonium-rejecting membranes was highlighted by introducing current and promising osmotic membrane-based applications in municipal wastewater reclamation processes.Subsequently,the connection between the micro/nano-structure of osmotic membranes and the transmembrane diffusion behavior of ammonia nitrogen was explored by analyzing the effects of membrane characteristics on ammonia nitrogen transport using the DSPM-DE model.Finally,precise methods for modifying membranes to enhance ammonia nitrogen rejection were proposed.This review aims to offer theoretical insights guiding the development of RO and FO membranes with superior ammonia nitrogen rejection for efficient reclamation of municipal wastewater.展开更多
Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy r...Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy remain an important,unresolved question.Methods:We investigated sex-biased molecular profiles across a multitude of biomarkers linked to immunotherapy responses.Multiomics data from major solid tumors in The Cancer Genome Atlas,with sufficient sample sizes(≥50 patients of each sex),were analyzed.Ninety-five molecular markers characterizing 4 distinct aspects of the tumor immune system were summarized and compared.The inverse probability of weights algorithm was used to generate well-balanced sex subgroups.Results:Our results showed that lung squamous cell carcinoma(LUSC),pancreatic adenocarcinoma,and liver hepatocellular carcinoma were the top 3 cancer types with extensive sex-biased biomarker profiles(31/95,15/95,and 14/95,respectively).Notably,although both were categorized as non–small cell lung carcinoma,LUSC harbored significantly more sex-biased immunological features than those of lung adenocarcinoma(p<0.01).We further explored the validity of this finding by analyzing ICI-responsive signatures and individual patient-level data for non–small cell lung carcinoma and found that sex had significant interaction effects on immunotherapy outcomes in LUSC(p_(interaction)<0.05),with women tending to derive greater benefits from ICIs than men.However,this difference was not apparent in the lung adenocarcinoma group(p_(interaction)=0.66),with men and women deriving comparable benefits.Conclusions:We systematically characterized sex-biased profiles of key molecular biomarkers predicting immunotherapy responses across solid tumors,which could pave the way for individualized therapeutic approaches for men and women.展开更多
This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a compr...This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a comprehensive literature review and case analysis,the research investigates the current state,challenges,and practical barriers to embedding NM into PHC systems,while proposing targeted strategies for improvement.The findings suggest that NM fosters stronger doctor-patient trust,enhances healthcare quality,and promotes humanistic care.However,primary hospitals face numerous challenges in advancing medical humanities,including a lack of trust between doctors and patients,tensions arising from the commercialization of healthcare,institutional limitations,unequal distribution of resources,and issues related to physicians'professional competencies and stress management.These interrelated obstacles detract from the quality of PHC services and the overall patient experience.Drawing on successful case studies from primary hospitals,the paper outlines effective strategies for overcoming these challenges.The study provides both theoretical and practical insights for advancing medical humanities in PHC,contributing to improvements in healthcare service quality and supporting the development of high standards in the healthcare sector.Ultimately,the findings aim to promote the broader adoption and ongoing refinement of NM within PHC institutions.展开更多
The catalyst's structural dynamics under reaction conditions critically determine their performance.We proved this indication by studying Ni nanoparticles supported on Mo_(2)CT_(x) MXene,where the average size dur...The catalyst's structural dynamics under reaction conditions critically determine their performance.We proved this indication by studying Ni nanoparticles supported on Mo_(2)CT_(x) MXene,where the average size during CO_(2) hydrogenation changed from 12.9 to 3.1 nm.A parallel increase of CO selectivity from 21.1%to 92.6%at 400℃ was observed,while the CO_(2) conversion rate remained at about 84.0 mmol·g_(cat)^(-1)·h^(-1).This transformation involved partial removal of Mo_(2)CT_(x) terminal groups,allowing direct interaction between Ni and Mo atoms instead of indirect coupling through-O terminations.The shift from a Ni-O-Mo to a Ni-Mo interaction enhanced electron transfer from Ni to Mo_(2)CT_(x),strengthening the metal-support interaction and driving Ni nanoparticle dispersion.In-situ mechanistic analysis and kinetic isotope studies revealed that Ni dispersion suppresses the formate and carboxyl pathway,promotes direct CO_(2) dissociation,and inhibits CO hydrogenation,shifting the primary product from CH_(4) to CO.These findings provide a strategy for designing highly selective and stable MXene-based catalysts through engineered metal-support interactions.展开更多
Biological neurons can be excited to maintain certain firing patterns following different external stimuli,and similar changes in electrical activities can be reproduced in some neural circuits by applying an external...Biological neurons can be excited to maintain certain firing patterns following different external stimuli,and similar changes in electrical activities can be reproduced in some neural circuits by applying an external voltage.Generic neural circuits are composed of capacitors,induction coils,resistors,and nonlinear resistors,and continuous energy exchange between the capacitive and inductive components is crucial for preserving output voltages.Incorporating nonlinear elements causes interactions between the charge flow across the capacitor and the induced electromotive force on the inductor.It is a challenge to explore the occurrence of nonlinear oscillation and coherence resonance in a neural circuit without using a capacitor and nonlinear resistor,and it considers the case lack of electric field energy.In this paper,a simple neural circuit is proposed that combines two inductors,one magnetic flux-controlled memristor(MFCM),and three resistors,with two constant voltage sources in the branch circuits used as reverse potentials in the ion channels.The field energy has an exact form,and it is stored in the circuit components as a magnetic field.Scale transformation is applied on the circuit equations and field energy function to obtain equivalent dimensionless forms of the memristive neuron and Hamilton energy.The reference values for the physical time and capacitance are represented by an appropriate combination of resistance and inductance,because the capacitance value is unavailable.The memristive neuron without capacitive effect still shows similar firing patterns,and coherence resonance is induced under noisy excitation.The emergence of coherence resonance can be predicted by calculating the distribution of the average energy<H>versus noise intensity,and the value for<H>reaches a maximum under coherence resonance.Finally,an adaptive law for parameter growth under energy control is proposed to control mode transitions in the electrical activity.The methodology and results of this work offer insights into the oscillatory mechanism of neural circuits,and showcase how magnetic field control can be used to manage neural activations.展开更多
The decarbonization of urban water systems is critical for achieving global climate goals,and reducing the carbon intensity of urban water systems necessitates a paradigm shift from traditional end-of-pipe treatment a...The decarbonization of urban water systems is critical for achieving global climate goals,and reducing the carbon intensity of urban water systems necessitates a paradigm shift from traditional end-of-pipe treatment approaches to alternative technological solutions and holistic planning.This study explores a comprehensive strategy for achieving sustainable urban water management that integrates a decentral-ized water system(DWS),source separation,and low-carbon water treatment technologies.DWS is fun-damental to implementing a sustainable urban water system.This study addresses the social contexts,costs,approaches,and benefits associated with DWS implementation,emphasizing the importance of its construction.Subsequently,the analysis focuses on the on-site source separation of grey water,feces,and yellow water in the DWS,which serves as the primary approach for wastewater reuse and N/P recov-ery for a sustainable urban water system.Following source separation,low-carbon water treatment tech-nologies based on resource conservation and recovery are thoroughly discussed.Specifically,resource conservation can be achieved through rainwater control,efficiency improvements,and low energy con-sumption,while resource recovery can be attained through carbon capturing and energy/nutrient recov-ery.Overall,in response to the challenges in current urban water management,this study proposes a comprehensive strategy that supports a sustainable urban water system,providing theoretical guidance for reducing carbon emissions.展开更多
According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and south...According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.展开更多
The aerospace and aviation industry has long been at the forefront of materials and processing technologies,driven by its ongoing demand for lightweight,highly reliable,and durable components.Precision manufacturing i...The aerospace and aviation industry has long been at the forefront of materials and processing technologies,driven by its ongoing demand for lightweight,highly reliable,and durable components.Precision manufacturing is a critical discipline that directly affects the performance,functionality,and safety of aircraft and aerospace vehicles.To meet the above-mentioned stringent requirements,advanced materials and cutting-edge processing technologies have evolved alongside aerospace innovations.展开更多
Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of S...Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.展开更多
Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emiss...Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.展开更多
Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of ...Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.展开更多
Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear...Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.展开更多
Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients ...Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.展开更多
Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV d...Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level Ⅱ), middle neck (levels Ⅲ and Va), and lower neck (levels Ⅳ and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium- or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P < 0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6% , 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.展开更多
Photocatalysis-self-Fenton system,i.e.,photo-catalytic H_(2)O_(2)generation and utilization in situ for OH radials production to remove organic pollutants with high-fluent degradation and mineralization performance po...Photocatalysis-self-Fenton system,i.e.,photo-catalytic H_(2)O_(2)generation and utilization in situ for OH radials production to remove organic pollutants with high-fluent degradation and mineralization performance pos-sesses such advantages as cleanliness,efficiency and safety.However,its degradation activity always suffers from the Fe(Ⅲ)/Fe(Ⅱ)cycle.For this reason,graphitic carbon interface-modified g-C_(3)N_(4)(CUCN)was fabricated to remarkably improve photocatalysis-self-Fenton degra-dation activity.The experiment results indicated that CUCN-2%photocatalyst,in which the loading percentage of graphitic carbon was 2%,demonstrated the optimum degradation performance among all the counterparts.The mineralization degree for RhB in 3 h over CUCN-2%reached 63.77%,nearly 3.35-fold higher than the pristine g-C_(3)N_(4).The significantly improved mineralization efficiency was ascribed to the promoted Fe(Ⅲ)/Fe(Ⅱ)cycle by photogenerated electrons,which leading to the higher utilization efficiency of H_(2)O_(2)through Fenton reaction,thereby producing more hydroxyl radicals.It is anticipated that our work could provide new insights for the design of photocatalysis-self-Fenton system with exceptional degradation performance for actual photocat-alytic applications.展开更多
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by the National Natural Science Foundation,China(Nos.52073224,12472141 and 12002248)the Natural Science Foundation of Shaanxi Province,China(Nos.2023KXJ-034 and 2023KXJ-005)+3 种基金Xi’an Science and Technology Plan Project,China(No.2022JH-ZCZC-0004)the Young Talent Fund of University Association for Science and Technology in Shaanxi,China(No.20210509)the Scientific Research Project of Shaanxi Provincial Education Department,China(No.22JC035)Shaanxi Outstanding Youth Science Fund Project,China(No.2024JC-JCQN-03).
文摘This paper reports the effects of fiber breakage defects and waviness defects on the compressive fatigue behavior and the progressive damage evolution process of 3D Multiaxial Braided Composites (3DMBCs). Combined with finite element compression simulation and ultra-depth microscope, the internal defect content of composites with different braiding angles was determined. The results demonstrate that the weakening effect of waviness and fiber breakage defects is greater than the strengthening effect of the braiding angle. This causes the fatigue resistance of 3DMBCs with the 31° braiding angle being better in both directions of 0° and 90°. The increase of 4° waviness and 10% fiber breakage defect results in the average fatigue life of composites being shortened by 48% and the energy consumption rate increased by 10% at 85% stress level in 90° compression direction. The alteration in loading direction modifies the included angle corresponding to the stress component. The stress component parallel to the fiber direction under compressive fatigue load leads to interfacial debonding in the composites, whereas the stress component perpendicular to the fiber direction results in pronounced shear failure.
基金supported by the National Natural Science Foundation of China(No.52300005)China Postdoctoral Science Foundation(No.2023TQ0098)+5 种基金Heilongjiang Postdoctoral Fund(No.LBH-Z23175)Heilongjiang Touyan Innovation Team Program(No.HIT-SE-01)the Crossover Fund of Medical Engineering Science of Harbin Institute of Technology(No.IR2021107)the National Natural Science Foundation of International(Regional)Cooperation and Exchange Project(No.51961125104)the State Key Laboratory of Urban Water Resource and Environment(Harbin Institute of Technology)(No.2022TS15)the Ecological and Environmental Protection Research Project of Heilongjiang Province(No.HST2022ST006).
文摘Halogenated aromatic disinfection byproducts(DBPs)are gradually receiving attention due to their high detection frequency and usually higher toxicity than regulated DBPs.In this study,we established a solid phase extraction(SPE)-LC-MS/MS method to simultaneously trace analyze 59 halogenated aromatic DBPs.The limits of detection and limits of quantification of halogenated aromatic DBPs ranged from 0.03 to 135.23 ng/L and from 0.1 to 450.76 ng/L,respectively.The range of recoveries and relative standard deviation(RSD)in river water were between 72.41%to 119.54%and 1.86%to 16.03%,respectively.Therefore,this method can be used to accurately analyze trace levels of halogenated aromatic DBPs in drinking water.The occurrence and transformation of halogenated aromatic DBPs were explored based on this method.In the chlorinated simulated source water and chlorinated river water,20 and 45 halogenated aromatic DBPs were determined,respectively.The active halogen species(HOCl,HOBr,and HOI)first reacted with natural organic matter(NOM)to form halogenated aromatic DBPs.Then,chlorine further reacted with the halogenated aromatic DBPs to convert them into small-molecule halogenated aliphatic DBPs through oxidation,electrophilic substitution,and hydrolysis reaction,etc.In the chlorinated simulated source water,chlorinated river water,and tap water,the toxicity contribution of bromoacetic acids(Br-HAAs)accounted for themajority(>71.16%).Given that halogenated aromatic DBPs are intermediate products of halogenated aliphatic DBPs,controlling the formation of halogenated aromatic DBPs is beneficial in decreasing the formation of halogenated aliphatic DBPs,thereby diminishing the toxicity of drinking water.
基金supported by National Natural Science Foundation of China(No.52200051)Harbin Institute of Technology(No.HC202236)Outstanding Youth Fund of Heilongjiang Natural Science Foundation(No.YQ2023E021)。
文摘With the global advancement of the circular economy,integrating reverse osmosis(RO)or forward osmosis(FO)with anaerobic membrane bioreactor(AnMBR)offers a promising approach to simultaneously generate high-grade reclaimed water,produce energy,and preserve valuable nutrients from municipal wastewater.However,the selectivity of these osmotic membranes towards ammonia nitrogen,a major component in municipal wastewater and anaerobic effluent,remains unsatisfactory due to its similar polarity and hydraulic radius to water molecules.Therefore,enhancing the ammonia nitrogen rejection of osmotic membranes is imperative to maximize the quality of reclaimed water and minimize the loss of ammonia nitrogen resources.Unfortunately,the current understanding of the mapping relationship between ammonia nitrogen transmembrane diffusion and the micro/nano-structure of osmotic membranes is not systematic,making precise optimization of the membranes challenging.Hence,this review comprehensively analyzed the diffusion behavior of ammonia nitrogen through osmotic membranes to lay the foundation for targeted regulation of membrane fine structure.Initially,the desire for ammonia/ammonium-rejecting membranes was highlighted by introducing current and promising osmotic membrane-based applications in municipal wastewater reclamation processes.Subsequently,the connection between the micro/nano-structure of osmotic membranes and the transmembrane diffusion behavior of ammonia nitrogen was explored by analyzing the effects of membrane characteristics on ammonia nitrogen transport using the DSPM-DE model.Finally,precise methods for modifying membranes to enhance ammonia nitrogen rejection were proposed.This review aims to offer theoretical insights guiding the development of RO and FO membranes with superior ammonia nitrogen rejection for efficient reclamation of municipal wastewater.
基金supported by grants from the Special Funding of China Postdoctoral Science Foundation(No.2022TQ0389)the National Natural Science Foundation of China(No.82303693)the National Postdoctoral Program for Innovative Talents(No.BX2021386)。
文摘Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy remain an important,unresolved question.Methods:We investigated sex-biased molecular profiles across a multitude of biomarkers linked to immunotherapy responses.Multiomics data from major solid tumors in The Cancer Genome Atlas,with sufficient sample sizes(≥50 patients of each sex),were analyzed.Ninety-five molecular markers characterizing 4 distinct aspects of the tumor immune system were summarized and compared.The inverse probability of weights algorithm was used to generate well-balanced sex subgroups.Results:Our results showed that lung squamous cell carcinoma(LUSC),pancreatic adenocarcinoma,and liver hepatocellular carcinoma were the top 3 cancer types with extensive sex-biased biomarker profiles(31/95,15/95,and 14/95,respectively).Notably,although both were categorized as non–small cell lung carcinoma,LUSC harbored significantly more sex-biased immunological features than those of lung adenocarcinoma(p<0.01).We further explored the validity of this finding by analyzing ICI-responsive signatures and individual patient-level data for non–small cell lung carcinoma and found that sex had significant interaction effects on immunotherapy outcomes in LUSC(p_(interaction)<0.05),with women tending to derive greater benefits from ICIs than men.However,this difference was not apparent in the lung adenocarcinoma group(p_(interaction)=0.66),with men and women deriving comparable benefits.Conclusions:We systematically characterized sex-biased profiles of key molecular biomarkers predicting immunotherapy responses across solid tumors,which could pave the way for individualized therapeutic approaches for men and women.
基金Supported by National Natural Science Foundation of China,No.82272204 and No.824721882022 Key Clinical Specialty of Zhejiang Province(Critical Care Medicine)+4 种基金“Pioneer”and“Leading Goose”R&D Program of Zhejiang,No.2023C03084Wenzhou Major Science and Technology Innovation Project,No.ZY2023005Central Guiding Local Technology Development,No.2024ZY01012Zhejiang Provincial College Students'Science and Technology Innovation Activity Program,No.2024R413A037National Innovation and Entrepreneurship Training Program for College Students,No.202410343030.
文摘This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a comprehensive literature review and case analysis,the research investigates the current state,challenges,and practical barriers to embedding NM into PHC systems,while proposing targeted strategies for improvement.The findings suggest that NM fosters stronger doctor-patient trust,enhances healthcare quality,and promotes humanistic care.However,primary hospitals face numerous challenges in advancing medical humanities,including a lack of trust between doctors and patients,tensions arising from the commercialization of healthcare,institutional limitations,unequal distribution of resources,and issues related to physicians'professional competencies and stress management.These interrelated obstacles detract from the quality of PHC services and the overall patient experience.Drawing on successful case studies from primary hospitals,the paper outlines effective strategies for overcoming these challenges.The study provides both theoretical and practical insights for advancing medical humanities in PHC,contributing to improvements in healthcare service quality and supporting the development of high standards in the healthcare sector.Ultimately,the findings aim to promote the broader adoption and ongoing refinement of NM within PHC institutions.
文摘The catalyst's structural dynamics under reaction conditions critically determine their performance.We proved this indication by studying Ni nanoparticles supported on Mo_(2)CT_(x) MXene,where the average size during CO_(2) hydrogenation changed from 12.9 to 3.1 nm.A parallel increase of CO selectivity from 21.1%to 92.6%at 400℃ was observed,while the CO_(2) conversion rate remained at about 84.0 mmol·g_(cat)^(-1)·h^(-1).This transformation involved partial removal of Mo_(2)CT_(x) terminal groups,allowing direct interaction between Ni and Mo atoms instead of indirect coupling through-O terminations.The shift from a Ni-O-Mo to a Ni-Mo interaction enhanced electron transfer from Ni to Mo_(2)CT_(x),strengthening the metal-support interaction and driving Ni nanoparticle dispersion.In-situ mechanistic analysis and kinetic isotope studies revealed that Ni dispersion suppresses the formate and carboxyl pathway,promotes direct CO_(2) dissociation,and inhibits CO hydrogenation,shifting the primary product from CH_(4) to CO.These findings provide a strategy for designing highly selective and stable MXene-based catalysts through engineered metal-support interactions.
基金supported by the National Natural Science Foundation of China(No.62361037).
文摘Biological neurons can be excited to maintain certain firing patterns following different external stimuli,and similar changes in electrical activities can be reproduced in some neural circuits by applying an external voltage.Generic neural circuits are composed of capacitors,induction coils,resistors,and nonlinear resistors,and continuous energy exchange between the capacitive and inductive components is crucial for preserving output voltages.Incorporating nonlinear elements causes interactions between the charge flow across the capacitor and the induced electromotive force on the inductor.It is a challenge to explore the occurrence of nonlinear oscillation and coherence resonance in a neural circuit without using a capacitor and nonlinear resistor,and it considers the case lack of electric field energy.In this paper,a simple neural circuit is proposed that combines two inductors,one magnetic flux-controlled memristor(MFCM),and three resistors,with two constant voltage sources in the branch circuits used as reverse potentials in the ion channels.The field energy has an exact form,and it is stored in the circuit components as a magnetic field.Scale transformation is applied on the circuit equations and field energy function to obtain equivalent dimensionless forms of the memristive neuron and Hamilton energy.The reference values for the physical time and capacitance are represented by an appropriate combination of resistance and inductance,because the capacitance value is unavailable.The memristive neuron without capacitive effect still shows similar firing patterns,and coherence resonance is induced under noisy excitation.The emergence of coherence resonance can be predicted by calculating the distribution of the average energy<H>versus noise intensity,and the value for<H>reaches a maximum under coherence resonance.Finally,an adaptive law for parameter growth under energy control is proposed to control mode transitions in the electrical activity.The methodology and results of this work offer insights into the oscillatory mechanism of neural circuits,and showcase how magnetic field control can be used to manage neural activations.
基金supported by the National Natural Science Foun-dation of China(52200008 and 52270043)the Young Elite Scien-tists Sponsorship Program by CAST,National Key Research and Developing Program of China(2023YFE0113800)+1 种基金the China Post-doctoral Science Foundation(2022M710034)the Chengde National Sustainable Development Agenda Innovation Demonstra-tion Zone Construction Technology Special Project(202202F003).
文摘The decarbonization of urban water systems is critical for achieving global climate goals,and reducing the carbon intensity of urban water systems necessitates a paradigm shift from traditional end-of-pipe treatment approaches to alternative technological solutions and holistic planning.This study explores a comprehensive strategy for achieving sustainable urban water management that integrates a decentral-ized water system(DWS),source separation,and low-carbon water treatment technologies.DWS is fun-damental to implementing a sustainable urban water system.This study addresses the social contexts,costs,approaches,and benefits associated with DWS implementation,emphasizing the importance of its construction.Subsequently,the analysis focuses on the on-site source separation of grey water,feces,and yellow water in the DWS,which serves as the primary approach for wastewater reuse and N/P recov-ery for a sustainable urban water system.Following source separation,low-carbon water treatment tech-nologies based on resource conservation and recovery are thoroughly discussed.Specifically,resource conservation can be achieved through rainwater control,efficiency improvements,and low energy con-sumption,while resource recovery can be attained through carbon capturing and energy/nutrient recov-ery.Overall,in response to the challenges in current urban water management,this study proposes a comprehensive strategy that supports a sustainable urban water system,providing theoretical guidance for reducing carbon emissions.
基金supported by the National Natural Science Foundation of China(no.81930072 and no.82172870 to J.Ma)by the Key-Area Research and Development Program of Guangdong Province(no.2019B020230002 to J.Ma).
文摘According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.
文摘The aerospace and aviation industry has long been at the forefront of materials and processing technologies,driven by its ongoing demand for lightweight,highly reliable,and durable components.Precision manufacturing is a critical discipline that directly affects the performance,functionality,and safety of aircraft and aerospace vehicles.To meet the above-mentioned stringent requirements,advanced materials and cutting-edge processing technologies have evolved alongside aerospace innovations.
文摘Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.
基金supported by grants from the Science and Technology Project of Guangzhou City,China(No.14570006)the Planned Science and Technology Project of Guangdong Province,China(No.2013B020400004)
文摘Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.
基金supported by grants from the Key Laboratory Construction Project of Guangzhou City,China (121800085)the Health & Medical Collaborative Innovation Project of Guangzhou City,China (201400000001)+2 种基金the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10)the National Natural Science Foundation of China (81201746)the Planned Science and Technology Project of Guangdong Province,China (2013B020400004)
文摘Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.
基金supported by grants from the Natural Science Foundation of Guangdong Province,China(No.2015A030310033)the Health&Medical Collaborative Innovation Project of Guangzhou City,China(No.201400000001)the Key Laboratory Construction Project of Guangzhou City(No.121800085)
文摘Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.
基金supported by Grants from the National Natural Science Foundation of China(Nos.81372409,81402532)the Sun Yat-sen University Clinical Research 5010 Program(No.2012011)
文摘Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.
文摘Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level Ⅱ), middle neck (levels Ⅲ and Va), and lower neck (levels Ⅳ and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium- or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P < 0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6% , 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.
基金financially supported by National Natural Science Foundation of China (No. 21906132)Department of Science and Technology of Sichuan Province (Nos. 2020YFG0158 and 2020YFH0162)Sichuan Provincial Engineering Laboratory of Livestock Manure Treatment and Recycling (Sichuan Normal University) (No. 202104)
文摘Photocatalysis-self-Fenton system,i.e.,photo-catalytic H_(2)O_(2)generation and utilization in situ for OH radials production to remove organic pollutants with high-fluent degradation and mineralization performance pos-sesses such advantages as cleanliness,efficiency and safety.However,its degradation activity always suffers from the Fe(Ⅲ)/Fe(Ⅱ)cycle.For this reason,graphitic carbon interface-modified g-C_(3)N_(4)(CUCN)was fabricated to remarkably improve photocatalysis-self-Fenton degra-dation activity.The experiment results indicated that CUCN-2%photocatalyst,in which the loading percentage of graphitic carbon was 2%,demonstrated the optimum degradation performance among all the counterparts.The mineralization degree for RhB in 3 h over CUCN-2%reached 63.77%,nearly 3.35-fold higher than the pristine g-C_(3)N_(4).The significantly improved mineralization efficiency was ascribed to the promoted Fe(Ⅲ)/Fe(Ⅱ)cycle by photogenerated electrons,which leading to the higher utilization efficiency of H_(2)O_(2)through Fenton reaction,thereby producing more hydroxyl radicals.It is anticipated that our work could provide new insights for the design of photocatalysis-self-Fenton system with exceptional degradation performance for actual photocat-alytic applications.