Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death p...Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.展开更多
Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at ...Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary.展开更多
Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and ...Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.展开更多
A system for fully automatic selection of welding specifications in resistance welding equipment has been developed to address the problem of workers frequently choosing the wrong specifications during manual welding ...A system for fully automatic selection of welding specifications in resistance welding equipment has been developed to address the problem of workers frequently choosing the wrong specifications during manual welding of multiple parts on a single machine in automobile factories. The system incorporates an automatic recognition system for different workpiece materials using the added machine fixture,visual detection system for nuts and bolts,and secondary graphical confirmation to ensure the correctness of specification calling. This system achieves reliable,fully automatic selection of welding specifications in resistance welding equipment and has shown significant effects in improving welding quality for massproduced workpieces,while solving the problem of specification calling errors that can occur with traditional methods involving process charts and code adjustments. This system is particularly suitable for promoting applications in manual welding of multiple parts on a single machine in automobile factories,ensuring correct specification calling and welding quality.展开更多
By considering the joint effects of the Kelvin-Helmholtz(KH) and Rayleigh-Taylor(RT) instabilities, this paper presents an interpretation of the wavy patterns that occur in explosive welding. It is assumed that the el...By considering the joint effects of the Kelvin-Helmholtz(KH) and Rayleigh-Taylor(RT) instabilities, this paper presents an interpretation of the wavy patterns that occur in explosive welding. It is assumed that the elasticity of the material at the interface effectively determines the wavelength, because explosive welding is basically a solid-state welding process. To this end, an analytical model of elastic hydrodynamic instabilities is proposed, and the most unstable mode is selected in the solid phase. Similar approaches have been widely used to study the interfacial behavior of solid metals in high-energy-density physics. By comparing the experimental and theoretical results, it is concluded that thermal softening,which significantly reduces the shear modulus, is necessary and sufficient for successful welding. The thermal softening is verified by theoretical analysis of the increase in temperature due to the impacting and sliding of the flyer and base plates, and some experimental observations are qualitatively validated.In summary, the combined effect of the KH and RT instabilities in solids determines the wavy morphology, and our theoretical results are in good qualitative agreement with experimental and numerical observations.展开更多
In order to overcome the problems of many pores,large deformation and unstable weld quality of traditional laser welded aluminumcopper alloy joints,a red-blue dual-beam laser source and a swinging laser were introduce...In order to overcome the problems of many pores,large deformation and unstable weld quality of traditional laser welded aluminumcopper alloy joints,a red-blue dual-beam laser source and a swinging laser were introduced for welding.T2 copper and 6063 aluminum thin plates were lap welded by coaxial dual-beam laser welding.The morphology of weld cross section was compared to explore the influence of process parameters on the formation of lap joints.The microstructure characteristics of the weld zone were observed and compared by optical microscope.The results show that the addition of laser beam swing can eliminate the internal pores of the weld.With the increase of the swing width,the weld depth decreases,and the weld width increases first and then decreases.The influence of welding speed on the weld cross section morphology is similar to that of swing width.With the increase of welding speed,the weld width increases first and then decreases,while the weld depth decreases all the time.This is because that the red laser is used as the main heat source to melt the base metals,with the increase of red laser power,the weld depth increases.As an auxiliary laser source,blue laser reduces the total energy consumption,consequently,the effective heat input increases and the spatter is restrained effectively.As a result,the increase of red laser power has an enhancement effect on the weld width and weld depth.When the swing width is 1.2 mm,the red laser power is 550 W,the blue laser power is 500 W,and the welding speed is 35 mm/s,the weld forming is the best.The lap joint of T2 copper and 6063 aluminum alloy thin plate can be connected stably with the hybrid of blue laser.The effect rules of laser beam swing on the weld formation were obtained,which improved the quality of the joints.展开更多
Ni-based superalloys are one of the most important materials employed in high-temperature applications within the aerospace and nuclear energy industries and in gas turbines due to their excellent corrosion,radiation,...Ni-based superalloys are one of the most important materials employed in high-temperature applications within the aerospace and nuclear energy industries and in gas turbines due to their excellent corrosion,radiation,fatigue resistance,and high-temperature strength.Linear friction welding(LFW)is a new joining technology with near-net-forming characteristics that can be used for the manu-facture and repair of a wide range of aerospace components.This paper reviews published works on LFW of Ni-based superalloys with the aim of understanding the characteristics of frictional heat generation and extrusion deformation,microstructures,mechanical proper-ties,flash morphology,residual stresses,creep,and fatigue of Ni-based superalloy weldments produced with LFW to enable future optim-um utilization of the LFW process.展开更多
To investigate the effects of material combinations and velocity conditions on atomic diffusion behavior near collision interfaces,this study simulates the atomic diffusion behavior near collision interfaces in Cu-Al,...To investigate the effects of material combinations and velocity conditions on atomic diffusion behavior near collision interfaces,this study simulates the atomic diffusion behavior near collision interfaces in Cu-Al,Al-Al and Cu-Cu combinations fabricated through collision welding using molecular dynamic(MD)simulation.The atomic diffusion behaviors are compared between similar metal combinations(Al-Al,Cu-Cu)and dissimilar metal combinations(Al-Cu).By combining the simulation results and classical diffusion theory,the diffusion coefficients for similar and dissimilar metal material combinations under different velocity conditions are obtained.The effects of material combinations and collision velocity on diffusion behaviors are also discussed.The diffusion behaviors of dissimilar material combinations strongly depend on the transverse velocity,whereas those of the similar material combinations are more dependent on the longitudinal velocity.These findings can provide guidance for optimizing welding parameters.展开更多
The high entropy alloys(HEAs)are the newly developed high-performance materials that have gained significant importance in defence,nuclear and aerospace sector due to their superior mechanical properties,heat resistan...The high entropy alloys(HEAs)are the newly developed high-performance materials that have gained significant importance in defence,nuclear and aerospace sector due to their superior mechanical properties,heat resistance,high temperature strength and corrosion resistance.These alloys are manufactured by the equal mixing or larger proportions of five or more alloying elements.HEAs exhibit superior mechanical performance compared to traditional engineering alloys because of the extensive alloying composition and higher entropy of mixing.Solid state welding(SSW)techniques such as friction stir welding(FSW),rotary friction welding(RFW),diffusion bonding(DB)and explosive welding(EW)have been efficiently deployed for improving the microstructural integrity and mechanical properties of welded HEA joints.The HEA interlayers revealed greater potential in supressing the formation of deleterious intermetallic phases and maximizing the mechanical properties of HEAs joints.The similar and dissimilar joining of HEAs has been manifested to be viable for HEA systems which further expands their industrial applications.Thus,the main objective of this review paper is to present a critical review of current state of research,challenges and opportunities and main directions in SSW of HEAs mainly CoCrFeNiMn and Al_xCoCrFeNi alloys.The state of the art of problems,progress and future outlook in SSW of HEAs are critically reviewed by considering the formation of phases,microstructural evolution and mechanical properties of HEAs joints.展开更多
The increase in number of people using the Internet leads to increased cyberattack opportunities.Advanced Persistent Threats,or APTs,are among the most dangerous targeted cyberattacks.APT attacks utilize various advan...The increase in number of people using the Internet leads to increased cyberattack opportunities.Advanced Persistent Threats,or APTs,are among the most dangerous targeted cyberattacks.APT attacks utilize various advanced tools and techniques for attacking targets with specific goals.Even countries with advanced technologies,like the US,Russia,the UK,and India,are susceptible to this targeted attack.APT is a sophisticated attack that involves multiple stages and specific strategies.Besides,TTP(Tools,Techniques,and Procedures)involved in the APT attack are commonly new and developed by an attacker to evade the security system.However,APTs are generally implemented in multiple stages.If one of the stages is detected,we may apply a defense mechanism for subsequent stages,leading to the entire APT attack failure.The detection at the early stage of APT and the prediction of the next step in the APT kill chain are ongoing challenges.This survey paper will provide knowledge about APT attacks and their essential steps.This follows the case study of known APT attacks,which will give clear information about the APT attack process—in later sections,highlighting the various detection methods defined by different researchers along with the limitations of the work.Data used in this article comes from the various annual reports published by security experts and blogs and information released by the enterprise networks targeted by the attack.展开更多
Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated ...Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).展开更多
Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods...Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods that covers the entire range of food categories,which limits the accurate risk assessment of dietary AGEs in human diseases.In this study,we first established an isotope dilution UHPLCQq Q-MS/MS-based method for simultaneous quantification of 10 major AGEs in foods.The contents of these AGEs were detected in 334 foods covering all main groups consumed in Western and Chinese populations.Nε-Carboxymethyllysine,methylglyoxal-derived hydroimidazolone isomers,and glyoxal-derived hydroimidazolone-1 are predominant AGEs found in most foodstuffs.Total amounts of AGEs were high in processed nuts,bakery products,and certain types of cereals and meats(>150 mg/kg),while low in dairy products,vegetables,fruits,and beverages(<40 mg/kg).Assessment of estimated daily intake implied that the contribution of food groups to daily AGE intake varied a lot under different eating patterns,and selection of high-AGE foods leads to up to a 2.7-fold higher intake of AGEs through daily meals.The presented AGE database allows accurate assessment of dietary exposure to these glycotoxins to explore their physiological impacts on human health.展开更多
BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further stu...BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.展开更多
BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therap...BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.展开更多
BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is cons...BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.展开更多
Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July...Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.展开更多
BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To ...BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.展开更多
The welding interface is crucial to the service safety of dissimilar metal weld(DMW)joints between stainless steel(SS)and low alloy(LA)steel.Different status of welding interfaces was prepared by cladding SS consumabl...The welding interface is crucial to the service safety of dissimilar metal weld(DMW)joints between stainless steel(SS)and low alloy(LA)steel.Different status of welding interfaces was prepared by cladding SS consumables to LA steel substrates with different heat inputs via tungsten inert gas arc welding(TIG),followed by a series of microstructural characterizations and hardness tests.Results showed that a hardening and transition layer(TL)would be generated along the welding interface,and the width and hardening degree of the TL would increase with the heat input.Meanwhile,heavy load hardness tests showed that highly severe inhomogeneous plastic deformation and the microcrack would be generated in the interfacial region and the welding interface respectively in the highest heat input sample(1.03 kJ/mm).These results indicate that the increase in heat input would deteriorate the bonding performance of DMW joints.Further microstructural observations showed that the higher hardening degree of the highest heat input sample was mainly attributed to the stronger grain boundary,solution,and dislocation strengthening effects.展开更多
基金Supported by Natural Science Foundation of Fujian Province,No.2021J011259.
文摘Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
基金financially supported by the National Science and Technology Major Project of China(No.J2019-VI-0004-0117)。
文摘Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary.
基金supported in part by the National Natural Science Foundation of China(62222301, 62073085, 62073158, 61890930-5, 62021003)the National Key Research and Development Program of China (2021ZD0112302, 2021ZD0112301, 2018YFC1900800-5)Beijing Natural Science Foundation (JQ19013)。
文摘Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.
文摘A system for fully automatic selection of welding specifications in resistance welding equipment has been developed to address the problem of workers frequently choosing the wrong specifications during manual welding of multiple parts on a single machine in automobile factories. The system incorporates an automatic recognition system for different workpiece materials using the added machine fixture,visual detection system for nuts and bolts,and secondary graphical confirmation to ensure the correctness of specification calling. This system achieves reliable,fully automatic selection of welding specifications in resistance welding equipment and has shown significant effects in improving welding quality for massproduced workpieces,while solving the problem of specification calling errors that can occur with traditional methods involving process charts and code adjustments. This system is particularly suitable for promoting applications in manual welding of multiple parts on a single machine in automobile factories,ensuring correct specification calling and welding quality.
基金the National Natural Science Foundation of China(Grant Nos.12002037 and 12141201).
文摘By considering the joint effects of the Kelvin-Helmholtz(KH) and Rayleigh-Taylor(RT) instabilities, this paper presents an interpretation of the wavy patterns that occur in explosive welding. It is assumed that the elasticity of the material at the interface effectively determines the wavelength, because explosive welding is basically a solid-state welding process. To this end, an analytical model of elastic hydrodynamic instabilities is proposed, and the most unstable mode is selected in the solid phase. Similar approaches have been widely used to study the interfacial behavior of solid metals in high-energy-density physics. By comparing the experimental and theoretical results, it is concluded that thermal softening,which significantly reduces the shear modulus, is necessary and sufficient for successful welding. The thermal softening is verified by theoretical analysis of the increase in temperature due to the impacting and sliding of the flyer and base plates, and some experimental observations are qualitatively validated.In summary, the combined effect of the KH and RT instabilities in solids determines the wavy morphology, and our theoretical results are in good qualitative agreement with experimental and numerical observations.
基金supported by Guangdong Science and Technology Plan Project(Grant No.20170902,No.20180902)Yangjiang Science and Technology Plan Project(Grant No.SDZX2020063)+1 种基金Shenzhen Key Projects of Innovation and Entrepreneurship Plan Technology(JSGG20210420091802007)Yunfu 2023 Science and Technology Plan Project(S2023020201).
文摘In order to overcome the problems of many pores,large deformation and unstable weld quality of traditional laser welded aluminumcopper alloy joints,a red-blue dual-beam laser source and a swinging laser were introduced for welding.T2 copper and 6063 aluminum thin plates were lap welded by coaxial dual-beam laser welding.The morphology of weld cross section was compared to explore the influence of process parameters on the formation of lap joints.The microstructure characteristics of the weld zone were observed and compared by optical microscope.The results show that the addition of laser beam swing can eliminate the internal pores of the weld.With the increase of the swing width,the weld depth decreases,and the weld width increases first and then decreases.The influence of welding speed on the weld cross section morphology is similar to that of swing width.With the increase of welding speed,the weld width increases first and then decreases,while the weld depth decreases all the time.This is because that the red laser is used as the main heat source to melt the base metals,with the increase of red laser power,the weld depth increases.As an auxiliary laser source,blue laser reduces the total energy consumption,consequently,the effective heat input increases and the spatter is restrained effectively.As a result,the increase of red laser power has an enhancement effect on the weld width and weld depth.When the swing width is 1.2 mm,the red laser power is 550 W,the blue laser power is 500 W,and the welding speed is 35 mm/s,the weld forming is the best.The lap joint of T2 copper and 6063 aluminum alloy thin plate can be connected stably with the hybrid of blue laser.The effect rules of laser beam swing on the weld formation were obtained,which improved the quality of the joints.
基金supported by the National Natural Science Foundation of China(Nos.52074228,52305420,and 51875470)the China Postdoctoral Science Foundation(No.2023M742830)the Xi’an Beilin District Science and Technology Planning Project,China(No.GX2349).
文摘Ni-based superalloys are one of the most important materials employed in high-temperature applications within the aerospace and nuclear energy industries and in gas turbines due to their excellent corrosion,radiation,fatigue resistance,and high-temperature strength.Linear friction welding(LFW)is a new joining technology with near-net-forming characteristics that can be used for the manu-facture and repair of a wide range of aerospace components.This paper reviews published works on LFW of Ni-based superalloys with the aim of understanding the characteristics of frictional heat generation and extrusion deformation,microstructures,mechanical proper-ties,flash morphology,residual stresses,creep,and fatigue of Ni-based superalloy weldments produced with LFW to enable future optim-um utilization of the LFW process.
基金supported by the Scientific Research Project of Hunan Provincial Department of Education(22C0642).
文摘To investigate the effects of material combinations and velocity conditions on atomic diffusion behavior near collision interfaces,this study simulates the atomic diffusion behavior near collision interfaces in Cu-Al,Al-Al and Cu-Cu combinations fabricated through collision welding using molecular dynamic(MD)simulation.The atomic diffusion behaviors are compared between similar metal combinations(Al-Al,Cu-Cu)and dissimilar metal combinations(Al-Cu).By combining the simulation results and classical diffusion theory,the diffusion coefficients for similar and dissimilar metal material combinations under different velocity conditions are obtained.The effects of material combinations and collision velocity on diffusion behaviors are also discussed.The diffusion behaviors of dissimilar material combinations strongly depend on the transverse velocity,whereas those of the similar material combinations are more dependent on the longitudinal velocity.These findings can provide guidance for optimizing welding parameters.
基金financially supported by Ministry of Science and Higher Education of the Russian Federation(Grant No.FENU-2023-0013)。
文摘The high entropy alloys(HEAs)are the newly developed high-performance materials that have gained significant importance in defence,nuclear and aerospace sector due to their superior mechanical properties,heat resistance,high temperature strength and corrosion resistance.These alloys are manufactured by the equal mixing or larger proportions of five or more alloying elements.HEAs exhibit superior mechanical performance compared to traditional engineering alloys because of the extensive alloying composition and higher entropy of mixing.Solid state welding(SSW)techniques such as friction stir welding(FSW),rotary friction welding(RFW),diffusion bonding(DB)and explosive welding(EW)have been efficiently deployed for improving the microstructural integrity and mechanical properties of welded HEA joints.The HEA interlayers revealed greater potential in supressing the formation of deleterious intermetallic phases and maximizing the mechanical properties of HEAs joints.The similar and dissimilar joining of HEAs has been manifested to be viable for HEA systems which further expands their industrial applications.Thus,the main objective of this review paper is to present a critical review of current state of research,challenges and opportunities and main directions in SSW of HEAs mainly CoCrFeNiMn and Al_xCoCrFeNi alloys.The state of the art of problems,progress and future outlook in SSW of HEAs are critically reviewed by considering the formation of phases,microstructural evolution and mechanical properties of HEAs joints.
文摘The increase in number of people using the Internet leads to increased cyberattack opportunities.Advanced Persistent Threats,or APTs,are among the most dangerous targeted cyberattacks.APT attacks utilize various advanced tools and techniques for attacking targets with specific goals.Even countries with advanced technologies,like the US,Russia,the UK,and India,are susceptible to this targeted attack.APT is a sophisticated attack that involves multiple stages and specific strategies.Besides,TTP(Tools,Techniques,and Procedures)involved in the APT attack are commonly new and developed by an attacker to evade the security system.However,APTs are generally implemented in multiple stages.If one of the stages is detected,we may apply a defense mechanism for subsequent stages,leading to the entire APT attack failure.The detection at the early stage of APT and the prediction of the next step in the APT kill chain are ongoing challenges.This survey paper will provide knowledge about APT attacks and their essential steps.This follows the case study of known APT attacks,which will give clear information about the APT attack process—in later sections,highlighting the various detection methods defined by different researchers along with the limitations of the work.Data used in this article comes from the various annual reports published by security experts and blogs and information released by the enterprise networks targeted by the attack.
文摘Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).
基金the financial support received from the Natural Science Foundation of China(32202202 and 31871735)。
文摘Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods that covers the entire range of food categories,which limits the accurate risk assessment of dietary AGEs in human diseases.In this study,we first established an isotope dilution UHPLCQq Q-MS/MS-based method for simultaneous quantification of 10 major AGEs in foods.The contents of these AGEs were detected in 334 foods covering all main groups consumed in Western and Chinese populations.Nε-Carboxymethyllysine,methylglyoxal-derived hydroimidazolone isomers,and glyoxal-derived hydroimidazolone-1 are predominant AGEs found in most foodstuffs.Total amounts of AGEs were high in processed nuts,bakery products,and certain types of cereals and meats(>150 mg/kg),while low in dairy products,vegetables,fruits,and beverages(<40 mg/kg).Assessment of estimated daily intake implied that the contribution of food groups to daily AGE intake varied a lot under different eating patterns,and selection of high-AGE foods leads to up to a 2.7-fold higher intake of AGEs through daily meals.The presented AGE database allows accurate assessment of dietary exposure to these glycotoxins to explore their physiological impacts on human health.
基金Our study has been approved by Medical Research Ethics Approval Committee(2023010122HN11C).
文摘BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.
基金Capital Health Development and Scientific Research Special Project,No.2022-2-2175.
文摘BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.
基金Supported by National Natural Science Foundation of China,No.31870993Fundamental Research Funds for the Central Universities,No.WK9110000005+3 种基金Anhui Provincial Health Research Project,No.AHWJ2022c020Anhui Medical University Campus Level Research Fund,No.2020xkj229Lu'an City Science and Technology Plan Project,No.2022Lakj009New Technology and Project of Lu'an People's Hospital,No.2021xjs10.
文摘BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.
文摘Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.
文摘BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.
文摘The welding interface is crucial to the service safety of dissimilar metal weld(DMW)joints between stainless steel(SS)and low alloy(LA)steel.Different status of welding interfaces was prepared by cladding SS consumables to LA steel substrates with different heat inputs via tungsten inert gas arc welding(TIG),followed by a series of microstructural characterizations and hardness tests.Results showed that a hardening and transition layer(TL)would be generated along the welding interface,and the width and hardening degree of the TL would increase with the heat input.Meanwhile,heavy load hardness tests showed that highly severe inhomogeneous plastic deformation and the microcrack would be generated in the interfacial region and the welding interface respectively in the highest heat input sample(1.03 kJ/mm).These results indicate that the increase in heat input would deteriorate the bonding performance of DMW joints.Further microstructural observations showed that the higher hardening degree of the highest heat input sample was mainly attributed to the stronger grain boundary,solution,and dislocation strengthening effects.