This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinom...This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.展开更多
BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with...BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.A total of 116 patients with advanced gastric cancer,admitted from January 2021 to December 2023,were selected and divided into two groups of 58 each using the random number table method.The control group received FOLFOX4 chemothe-rapy(oxaliplatin+calcium+folinate+5-fluorouracil)combined with intravenous sindilizumab.The observation group received the same treatment as the control group,supplemented by oral administration of Senqi Shiyiwei granules.Both groups underwent treatment cycles of 3 weeks,with a minimum of two cycles.The therapeutic efficacy,immune mechanisms,and treatment-related toxicity and side effects were compared between the groups.The objective remission rate in the observation group(55.17%)was higher than that of the control group(36.21%)(P<0.05).After two treatment cycle,CD3+,CD4+,and CD4+/CD8+levels were higher in the observation group compared to the control group,while CD8+,regulatory T cells,and natural killer cells were lower(P<0.05).Additionally,the incidence of leukopenia,nausea,and vomiting was lower in observed group(P<0.05).No significant differences were observed in the incidence of other adverse reactions(P>0.05).CONCLUSION Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts,making it a valuable option in clinical treatment.展开更多
BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for surgery.PC is prone to rec...BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for surgery.PC is prone to recurrence and metastasis,and the antitumor effect of chemotherapy is notably limited.CASE SUMMARY Histopathological analysis of a 53-year-old female PC patient who underwent Whipple surgery revealed poorly differentiated tumor cells infiltrating nerves,lymphatics,and blood vessels.The patient received two different first-line chemotherapy regimens consecutively;however,both regimens struggled to control disease progression.During this period,the patient underwent liver metastasis ablation surgery,Candida albicans liver abscess,and stereotactic body radiotherapy.With the addition of camrelizumab to the modified FOLFIRINOX regimen,tumor control was achieved.The patient subsequently refused to continue chemotherapy,and the antitumor regimen was changed to a combination of camrelizumab and apatinib.After patients received a combination of immunotherapy and targeted therapy,the length of hospital stay was significantly reduced.Furthermore,all side effects were within acceptable limits,leading to an improved quality of life and prolonged progression-free survival.Unfortunately,the pain associated with cancer,coupled with the side effects of opioid analgesics,has led the patient to reject all available anticancer treatment options.Approximately one month after camrelizumab and apatinib were discontinued without medical authorization,the PC recurred and rapidly progressed to widespread metastasis,ultimately leading to the patient's death approximately one month later.The overall survival was 2 years.CONCLUSION Immunotherapy and targeted therapy have the potential to increase both the quality of life and survival time of PC patients,particularly those whose tumor progression is not effectively controlled by chemotherapy alone.Nevertheless,further clinical trials are necessary to validate these findings.展开更多
People with advanced chronic liver disease(ACLD)have an enhanced risk of malnutrition,which has multifactorial etiology and is mainly linked to a reduced energy and protein intake;malnutrition is critical for patients...People with advanced chronic liver disease(ACLD)have an enhanced risk of malnutrition,which has multifactorial etiology and is mainly linked to a reduced energy and protein intake;malnutrition is critical for patients with cirrhosis since it is often associated with sarcopenia,a skeletal muscle depletion with a loss of muscle mass and function.Late-evening snacks have been extensively studied,and guidelines are recommended to counteract the effects of prolonged fasting at night in patients with ACLD.However,it has not been fully explored whether late evening snacking is clarified as a milestone to address the nutritional needs of people with ACLD or whether it has a potential role in improving body compo-sition.In this randomised control trial,Yu et al demonstrated that long-term nocturnal snacks have the potential to significantly improve body composition by body fat mass,visceral fat area and body cell mass in patients with ACLD.While the improvement in skeletal muscle mass was minor,the promising results in other compositions provide hope for future research and patient care.展开更多
This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved c...This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.展开更多
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
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
Smart wearables equipped with integrated flexible actuators possess the ability to autonomously respond and adapt to changes in the environment.Fibrous textiles have been recognised as promising platforms for integrat...Smart wearables equipped with integrated flexible actuators possess the ability to autonomously respond and adapt to changes in the environment.Fibrous textiles have been recognised as promising platforms for integrating flexible actuators and wearables owing to their superior body compliance,lightweight nature,and programmable architectures.Various studies related to textile actuators in smart wearables have been recently reported.However,the review focusing on the advanced design of these textile actuator technologies for smart wearables is lacking.Herein,a timely and thorough review of the progress achieved in this field over the past five years is presented.This review focuses on the advanced design concepts for textile actuators in smart wearables,covering functional materials,innovative architecture configurations,external stimuli,and their applications in smart wearables.The primary aspects focus on actuating materials,formation techniques of textile architecture,actuating behaviour and performance metrics of textile actuators,various applications in smart wearables,and the design challenges for next-generation smart wearables.Ultimately,conclusive perspectives are highlighted.展开更多
BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal the...BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.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
Electronic packaging is an essential branch of electronic engineering that aims to protect electronic,microelec-tronic,and nanoelectronic systems from environmental conditions.The design of electronic packaging is hig...Electronic packaging is an essential branch of electronic engineering that aims to protect electronic,microelec-tronic,and nanoelectronic systems from environmental conditions.The design of electronic packaging is highly complex and requires the consideration of multi-physics phenomena,such as thermal transport,electromagnetic fields,and mechanical stress.This review presents a comprehensive overview of the multiphysics coupling of electric,magnetic,thermal,mechanical,and fluid fields,which are crucial for assessing the performance and reliability of electronic devices.The recent advancements in multi-scale simulation techniques are also system-atically summarized,such as finite element methods at the macroscopic scale,molecular dynamics and density functional theory at the microscopic scale,and particularly machine learning methods for bridging different scales.Additionally,we illustrate how these methods can be applied to study various aspects of electronic pack-aging,such as material properties,interfacial failure,thermal management,electromigration,and stress analysis.The challenges and the potential applications of multi-scale simulation techniques in electronic packaging are also highlighted.Further,some future directions for multi-scale simulation techniques in electronic packaging are concluded for further investigation.展开更多
In the post-Moore era,advanced packaging is becoming more critical to meet the everlasting demands of elec-tronic products with smaller size,more powerful performance and lower cost.In this paper,developments in advan...In the post-Moore era,advanced packaging is becoming more critical to meet the everlasting demands of elec-tronic products with smaller size,more powerful performance and lower cost.In this paper,developments in advanced packaging have been discussed,such as 3D IC packaging,fan-out packaging,and chiplet packaging.Insights on the major advantages and challenges have also been briefly introduced.Our prospects about the solu-tions to some fundamental issues in sustainable development of advanced packaging have also been elucidated.The critical aspects and opportunities lie in standardization,co-design tools,new handling technologies,as well as multi-scale modeling and simulation.展开更多
In this paper,the mission and the thermal environment of the Solar Close Observations and Proximity Experiments(SCOPE)spacecraft are analyzed,and an advanced thermal management system(ATMS)is designed for it.The relat...In this paper,the mission and the thermal environment of the Solar Close Observations and Proximity Experiments(SCOPE)spacecraft are analyzed,and an advanced thermal management system(ATMS)is designed for it.The relationship and functions of the integrated database,the intelligent thermal control system and the efficient liquid cooling system in the ATMS are elaborated upon.For the complex thermal field regulation system and extreme space thermal environment,a modular simulation and thermal field planning method are proposed,and the feasibility of the planning algorithm is verified by numerical simulation.A solar array liquid cooling system is developed,and the system simulation results indicate that the temperatures of the solar arrays meet the requirements as the spacecraft flies by perihelion and aphelion.The advanced thermal management study supports the development of the SCOPE program and provides a reference for the thermal management in other deep-space exploration programs.展开更多
Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition...Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.展开更多
High-concentration phenol wastewater is pollutant of concern that pose significant risks to human health and the environment.Three-dimensional electrocatalytic oxidation is one of the most promising wastewater treatme...High-concentration phenol wastewater is pollutant of concern that pose significant risks to human health and the environment.Three-dimensional electrocatalytic oxidation is one of the most promising wastewater treatment technologies because of its high treatment efficiency,low energy consumption and low secondary pollution.Lower-cost and higher-performance particles still faces great challenges.In this work,metal oxide particle electrodes were prepared using granular activated carbon(GAC)as a substrate to study the degradation of phenol by three-dimensional electrocatalytic oxidation.GAC particle electrodes loaded with different monometallic oxides(Mn,Fe,Co,Ce)and bimetallic oxides(Fe and Ce)were prepared by the impregnation method.The effectiveness of the particle electrodes in degrading phenol was greatly improved after active components loading.Among all monometallic oxide particle electrodes,the concentration degradation efficiency was in the order of Ce/GAC>Co/GAC>Mn/GAC>Fe/GAC,and the COD degradation efficiency was Ce/GAC>Fe/GAC>Co/GAC>Mn/GAC.After optimizing the loading metal type and loading amount,it was found that the 1.1%Fe-2.7%Ce/GAC particle electrode perform the best,with a phenol degradation efficiency of 95.48%,a COD degradation rate of 94.35%,an energy consumption of 0.75 kW·h·kg^(-1)COD.This lower-cost and higher-performance particle highlights a reliable route for solving the problem of particle electrode materials limiting the efficient treatment of phenol-containing wastewater.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
文摘This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.
文摘BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.A total of 116 patients with advanced gastric cancer,admitted from January 2021 to December 2023,were selected and divided into two groups of 58 each using the random number table method.The control group received FOLFOX4 chemothe-rapy(oxaliplatin+calcium+folinate+5-fluorouracil)combined with intravenous sindilizumab.The observation group received the same treatment as the control group,supplemented by oral administration of Senqi Shiyiwei granules.Both groups underwent treatment cycles of 3 weeks,with a minimum of two cycles.The therapeutic efficacy,immune mechanisms,and treatment-related toxicity and side effects were compared between the groups.The objective remission rate in the observation group(55.17%)was higher than that of the control group(36.21%)(P<0.05).After two treatment cycle,CD3+,CD4+,and CD4+/CD8+levels were higher in the observation group compared to the control group,while CD8+,regulatory T cells,and natural killer cells were lower(P<0.05).Additionally,the incidence of leukopenia,nausea,and vomiting was lower in observed group(P<0.05).No significant differences were observed in the incidence of other adverse reactions(P>0.05).CONCLUSION Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts,making it a valuable option in clinical treatment.
文摘BACKGROUND The 5-year survival rate for patients with pancreatic cancer(PC)is 4%-12%.Surgery is the only treatment that offers curative potential,but only 15%-20%of patients are eligible for surgery.PC is prone to recurrence and metastasis,and the antitumor effect of chemotherapy is notably limited.CASE SUMMARY Histopathological analysis of a 53-year-old female PC patient who underwent Whipple surgery revealed poorly differentiated tumor cells infiltrating nerves,lymphatics,and blood vessels.The patient received two different first-line chemotherapy regimens consecutively;however,both regimens struggled to control disease progression.During this period,the patient underwent liver metastasis ablation surgery,Candida albicans liver abscess,and stereotactic body radiotherapy.With the addition of camrelizumab to the modified FOLFIRINOX regimen,tumor control was achieved.The patient subsequently refused to continue chemotherapy,and the antitumor regimen was changed to a combination of camrelizumab and apatinib.After patients received a combination of immunotherapy and targeted therapy,the length of hospital stay was significantly reduced.Furthermore,all side effects were within acceptable limits,leading to an improved quality of life and prolonged progression-free survival.Unfortunately,the pain associated with cancer,coupled with the side effects of opioid analgesics,has led the patient to reject all available anticancer treatment options.Approximately one month after camrelizumab and apatinib were discontinued without medical authorization,the PC recurred and rapidly progressed to widespread metastasis,ultimately leading to the patient's death approximately one month later.The overall survival was 2 years.CONCLUSION Immunotherapy and targeted therapy have the potential to increase both the quality of life and survival time of PC patients,particularly those whose tumor progression is not effectively controlled by chemotherapy alone.Nevertheless,further clinical trials are necessary to validate these findings.
文摘People with advanced chronic liver disease(ACLD)have an enhanced risk of malnutrition,which has multifactorial etiology and is mainly linked to a reduced energy and protein intake;malnutrition is critical for patients with cirrhosis since it is often associated with sarcopenia,a skeletal muscle depletion with a loss of muscle mass and function.Late-evening snacks have been extensively studied,and guidelines are recommended to counteract the effects of prolonged fasting at night in patients with ACLD.However,it has not been fully explored whether late evening snacking is clarified as a milestone to address the nutritional needs of people with ACLD or whether it has a potential role in improving body compo-sition.In this randomised control trial,Yu et al demonstrated that long-term nocturnal snacks have the potential to significantly improve body composition by body fat mass,visceral fat area and body cell mass in patients with ACLD.While the improvement in skeletal muscle mass was minor,the promising results in other compositions provide hope for future research and patient care.
基金Supported by Jilin Provincial Natural Science Foundation,No.YDZJ202401650ZYTS。
文摘This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.
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funding support(Project No.G-YWA2,1-YXAK,and 1-WZ1Y)of this work.
文摘Smart wearables equipped with integrated flexible actuators possess the ability to autonomously respond and adapt to changes in the environment.Fibrous textiles have been recognised as promising platforms for integrating flexible actuators and wearables owing to their superior body compliance,lightweight nature,and programmable architectures.Various studies related to textile actuators in smart wearables have been recently reported.However,the review focusing on the advanced design of these textile actuator technologies for smart wearables is lacking.Herein,a timely and thorough review of the progress achieved in this field over the past five years is presented.This review focuses on the advanced design concepts for textile actuators in smart wearables,covering functional materials,innovative architecture configurations,external stimuli,and their applications in smart wearables.The primary aspects focus on actuating materials,formation techniques of textile architecture,actuating behaviour and performance metrics of textile actuators,various applications in smart wearables,and the design challenges for next-generation smart wearables.Ultimately,conclusive perspectives are highlighted.
基金Supported by Natural Science Foundation of Hainan Province,No.823RC609.
文摘BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.
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.
基金supported by the National Natural Science Foundation of China(U2241244).
文摘Electronic packaging is an essential branch of electronic engineering that aims to protect electronic,microelec-tronic,and nanoelectronic systems from environmental conditions.The design of electronic packaging is highly complex and requires the consideration of multi-physics phenomena,such as thermal transport,electromagnetic fields,and mechanical stress.This review presents a comprehensive overview of the multiphysics coupling of electric,magnetic,thermal,mechanical,and fluid fields,which are crucial for assessing the performance and reliability of electronic devices.The recent advancements in multi-scale simulation techniques are also system-atically summarized,such as finite element methods at the macroscopic scale,molecular dynamics and density functional theory at the microscopic scale,and particularly machine learning methods for bridging different scales.Additionally,we illustrate how these methods can be applied to study various aspects of electronic pack-aging,such as material properties,interfacial failure,thermal management,electromigration,and stress analysis.The challenges and the potential applications of multi-scale simulation techniques in electronic packaging are also highlighted.Further,some future directions for multi-scale simulation techniques in electronic packaging are concluded for further investigation.
基金funded by National Natural Science Foundation of China(62274122 and 62004144)Guangdong Basic and Applied Basic Research Foundation(2021A1515010651)Hubei Provincial Natural Science Foundation of China(2020CFA032).
文摘In the post-Moore era,advanced packaging is becoming more critical to meet the everlasting demands of elec-tronic products with smaller size,more powerful performance and lower cost.In this paper,developments in advanced packaging have been discussed,such as 3D IC packaging,fan-out packaging,and chiplet packaging.Insights on the major advantages and challenges have also been briefly introduced.Our prospects about the solu-tions to some fundamental issues in sustainable development of advanced packaging have also been elucidated.The critical aspects and opportunities lie in standardization,co-design tools,new handling technologies,as well as multi-scale modeling and simulation.
文摘In this paper,the mission and the thermal environment of the Solar Close Observations and Proximity Experiments(SCOPE)spacecraft are analyzed,and an advanced thermal management system(ATMS)is designed for it.The relationship and functions of the integrated database,the intelligent thermal control system and the efficient liquid cooling system in the ATMS are elaborated upon.For the complex thermal field regulation system and extreme space thermal environment,a modular simulation and thermal field planning method are proposed,and the feasibility of the planning algorithm is verified by numerical simulation.A solar array liquid cooling system is developed,and the system simulation results indicate that the temperatures of the solar arrays meet the requirements as the spacecraft flies by perihelion and aphelion.The advanced thermal management study supports the development of the SCOPE program and provides a reference for the thermal management in other deep-space exploration programs.
基金This work was supported by the National Key Research and Development Program of China(Grant No.2021YFA1201100)the National Natural Science Foundation of China(Grant No.82072657).
文摘Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.
文摘High-concentration phenol wastewater is pollutant of concern that pose significant risks to human health and the environment.Three-dimensional electrocatalytic oxidation is one of the most promising wastewater treatment technologies because of its high treatment efficiency,low energy consumption and low secondary pollution.Lower-cost and higher-performance particles still faces great challenges.In this work,metal oxide particle electrodes were prepared using granular activated carbon(GAC)as a substrate to study the degradation of phenol by three-dimensional electrocatalytic oxidation.GAC particle electrodes loaded with different monometallic oxides(Mn,Fe,Co,Ce)and bimetallic oxides(Fe and Ce)were prepared by the impregnation method.The effectiveness of the particle electrodes in degrading phenol was greatly improved after active components loading.Among all monometallic oxide particle electrodes,the concentration degradation efficiency was in the order of Ce/GAC>Co/GAC>Mn/GAC>Fe/GAC,and the COD degradation efficiency was Ce/GAC>Fe/GAC>Co/GAC>Mn/GAC.After optimizing the loading metal type and loading amount,it was found that the 1.1%Fe-2.7%Ce/GAC particle electrode perform the best,with a phenol degradation efficiency of 95.48%,a COD degradation rate of 94.35%,an energy consumption of 0.75 kW·h·kg^(-1)COD.This lower-cost and higher-performance particle highlights a reliable route for solving the problem of particle electrode materials limiting the efficient treatment of phenol-containing wastewater.
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).