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
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
The development of intestinal anastomosis techniques,including hand suturing,stapling,and compression anastomoses,has been a significant advancement in surgical practice.These methods aim to prevent leakage and minimi...The development of intestinal anastomosis techniques,including hand suturing,stapling,and compression anastomoses,has been a significant advancement in surgical practice.These methods aim to prevent leakage and minimize tissue fibrosis,which can lead to stricture formation.The healing process involves various phases:hemostasis and inflammation,proliferation,and remodeling.Mechanical staplers and sutures can cause inflammation and fibrosis due to the release of profibrotic chemokines.Compression anastomosis devices,including those made of nickel-titanium alloy,offer a minimally invasive option for various surgical challenges and have shown safety and efficacy.However,despite advancements,anastomotic techniques are evaluated based on leakage risk,with complications being a primary concern.Newer devices like Magnamosis use magnetic rings for compression anastomosis,demonstrating greater strength and patency compared to stapling.Magnetic technology is also being explored for other medical treatments.While there are promising results,particularly in animal models,the realworld application in humans is limited,and further research is needed to assess their safety and practicality.展开更多
The technology of tunnel boring machine(TBM)has been widely applied for underground construction worldwide;however,how to ensure the TBM tunneling process safe and efficient remains a major concern.Advance rate is a k...The technology of tunnel boring machine(TBM)has been widely applied for underground construction worldwide;however,how to ensure the TBM tunneling process safe and efficient remains a major concern.Advance rate is a key parameter of TBM operation and reflects the TBM-ground interaction,for which a reliable prediction helps optimize the TBM performance.Here,we develop a hybrid neural network model,called Attention-ResNet-LSTM,for accurate prediction of the TBM advance rate.A database including geological properties and TBM operational parameters from the Yangtze River Natural Gas Pipeline Project is used to train and test this deep learning model.The evolutionary polynomial regression method is adopted to aid the selection of input parameters.The results of numerical exper-iments show that our Attention-ResNet-LSTM model outperforms other commonly-used intelligent models with a lower root mean square error and a lower mean absolute percentage error.Further,parametric analyses are conducted to explore the effects of the sequence length of historical data and the model architecture on the prediction accuracy.A correlation analysis between the input and output parameters is also implemented to provide guidance for adjusting relevant TBM operational parameters.The performance of our hybrid intelligent model is demonstrated in a case study of TBM tunneling through a complex ground with variable strata.Finally,data collected from the Baimang River Tunnel Project in Shenzhen of China are used to further test the generalization of our model.The results indicate that,compared to the conventional ResNet-LSTM model,our model has a better predictive capability for scenarios with unknown datasets due to its self-adaptive characteristic.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
Recently,the World Journal of Gastrointestinal Oncology published an article entitled“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A cas...Recently,the World Journal of Gastrointestinal Oncology published an article entitled“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”,in which the authors shared their successful experience with complete surgical resection after multidisciplinary conversion therapy.The study by Chu et al demonstrates the great challenges that the advanced hepatocellular carcinoma(HCC)poses to surgical oncology,reveals the complexity of conversion therapy for unresectable HCC,emphasizes the important role of a multidisciplinary management model in conversion therapy,and enriches our understanding of the dynamics of personalized treatment for different patients.At present,conversion therapy is a hot research topic in the treatment of unresectable HCC,which has brought new hope to many patients with moderately advanced HCC.However,there are still many urgent problems to be solved in conversion therapy.Here,we would like to further discuss the advances and challenges of conversion therapy for unresectable HCC with the authors and the general readers.展开更多
Zinc-ion batteries(ZIBs) are recognized as potential energy storage devices due to their advantages of low cost, high energy density, and environmental friendliness. However, zinc anodes are subject to unavoidable zin...Zinc-ion batteries(ZIBs) are recognized as potential energy storage devices due to their advantages of low cost, high energy density, and environmental friendliness. However, zinc anodes are subject to unavoidable zinc dendrites, passivation, corrosion, and hydrogen evolution reactions during the charging and discharging of batteries, becoming obstacles to the practical application of ZIBs. Appropriate zinc metal-free anodes provide a higher working potential than metallic zinc anodes, effectively solving the problems of zinc dendrites, hydrogen evolution, and side reactions during the operation of metallic zinc anodes. The improvement in the safety and cycle life of batteries creates conditions for further commercialization of ZIBs. Therefore, this work systematically introduces the research progress of zinc metal-free anodes in “rocking chair” ZIBs. Zinc metal-free anodes are mainly discussed in four categories: transition metal oxides,transition metal sulfides, MXene(two dimensional transition metal carbide) composites, and organic compounds, with discussions on their properties and zinc storage mechanisms. Finally, the outlook for the development of zinc metal-free anodes is proposed. This paper is expected to provide a reference for the further promotion of commercial rechargeable ZIBs.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
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
Embedded memory,which heavily relies on the manufacturing process,has been widely adopted in various industrial applications.As the field of embedded memory continues to evolve,innovative strategies are emerging to en...Embedded memory,which heavily relies on the manufacturing process,has been widely adopted in various industrial applications.As the field of embedded memory continues to evolve,innovative strategies are emerging to enhance performance.Among them,resistive random access memory(RRAM)has gained significant attention due to its numerousadvantages over traditional memory devices,including high speed(<1 ns),high density(4 F^(2)·n^(-1)),high scalability(~nm),and low power consumption(~pJ).This review focuses on the recent progress of embedded RRAM in industrial manufacturing and its potentialapplications.It provides a brief introduction to the concepts and advantages of RRAM,discusses the key factors that impact its industrial manufacturing,and presents the commercial progress driven by cutting-edge nanotechnology,which has been pursued by manysemiconductor giants.Additionally,it highlights the adoption of embedded RRAM in emerging applications within the realm of the Internet of Things and future intelligent computing,with a particular emphasis on its role in neuromorphic computing.Finally,the review discusses thecurrent challenges and provides insights into the prospects of embedded RRAM in the era of big data and artificial intelligence.展开更多
Realizing fast and continuous generation of reactive oxygen species(ROSs)via iron-based advanced oxidation processes(AOPs)is significant in the environmental and biological fields.However,current AOPs assisted by co-c...Realizing fast and continuous generation of reactive oxygen species(ROSs)via iron-based advanced oxidation processes(AOPs)is significant in the environmental and biological fields.However,current AOPs assisted by co-catalysts still suffer from the poor mass/electron transfer and non-durable promotion effect,giving rise to the sluggish Fe^(2+)/Fe^(3+)cycle and low dynamic concentration of Fe^(2+)for ROS production.Herein,we present a three-dimensional(3D)macroscale co-catalyst functionalized with molybdenum disulfide(MoS_(2))to achieve ultra-efficient Fe^(2+)regeneration(equilibrium Fe^(2+)ratio of 82.4%)and remarkable stability(more than 20 cycles)via a circulating flow-through process.Unlike the conventional batch-type reactor,experiments and computational fluid dynamics simulations demonstrate that the optimal utilization of the 3D active area under the flow-through mode,initiated by the convectionenhanced mass/charge transfer for Fe^(2+)reduction and then strengthened by MoS_(2)-induced flow rotation for sufficient reactant mixing,is crucial for oxidant activation and subsequent ROS generation.Strikingly,the flow-through co-catalytic system with superwetting capabilities can even tackle the intricate oily wastewater stabilized by different surfactants without the loss of pollutant degradation efficiency.Our findings highlight an innovative co-catalyst system design to expand the applicability of AOPs based technology,especially in large-scale complex wastewater treatment.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
Mandibular advancement devices(MADs)are widely used treatments for obstructive sleep apnea.MADs function by advancing the lower jaw to open the upper airway.To increase patient comfort,most patients allow the mouth to...Mandibular advancement devices(MADs)are widely used treatments for obstructive sleep apnea.MADs function by advancing the lower jaw to open the upper airway.To increase patient comfort,most patients allow the mouth to be opened.However,not all systems maintain the lower jaw in a forward position during mouth opening,which results in the production of a retrusion that favors the collapse of the upper airway.Furthermore,the kinematic behavior of the mechanism formed by the mandible-device assembly depends on jaw morphology.This means that,during mouth opening,some devices cause lower jaw protrusion in some patients,but cause its retraction in others.In this study,we report the behavior of well-known devices currently on themarket.To do so,we developed a kinematic model of the lower jawdevice assembly.Thismodelwas validated for all devices analyzed using a high-resolution camera system.Our results show that some of the devices analyzed here did not produce the correct behavior during patient mouth opening.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
Antibiotic resistant bacteria(ARB)with antibiotic resistance genes(ARGs)can reduce or eliminate the effectiveness of antibiotics and thus threaten human health.The United Nations Environment Programme considers antibi...Antibiotic resistant bacteria(ARB)with antibiotic resistance genes(ARGs)can reduce or eliminate the effectiveness of antibiotics and thus threaten human health.The United Nations Environment Programme considers antibiotic resistance the first of six emerging issues of concern.Advanced oxidation processes(AOPs)that combine ultraviolet(UV)irradiation and chemical oxidation(primarily chlorine,hydrogen peroxide,and persulfate)have attracted increasing interest as advanced water and wastewater treatment technologies.These integrated technologies have been reported to significantly elevate the efficiencies of ARB inactivation and ARG degradation compared with direct UV irradiation or chemical oxidation alone due to the generation of multiple reactive species.In this study,the performance and underlying mechanisms of UV/chlorine,UV/hydrogen peroxide,and UV/persulfate processes for controlling ARB and ARGs were reviewed based on recent studies.Factors affecting the process-specific efficiency in controlling ARB and ARGs were discussed,including biotic factors,oxidant dose,UV fluence,pH,and water matrix properties.In addition,the cost-effectiveness of the UV-based AOPs was evaluated using the concept of electrical energy per order.The UV/chlorine process exhibited a higher efficiency with lower energy consumption than other UV-based AOPs in the wastewater matrix,indicating its potential for ARB inactivation and ARG degradation in wastewater treatment.Further studies are required to address the trade-off between toxic byproduct formation and the energy efficiency of the UV/chlorine process in real wastewater to facilitate its optimization and application in the control of ARB and ARGs.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
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 Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate t...BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.展开更多
Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely comme...Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely commercial application and development of LSB is mainly hindered by serious“shuttle effect”of lithium polysulfides(Li PSs),slow reaction kinetics,notorious lithium dendrites,etc.In various structures of LSB materials,array structured materials,possessing the composition of ordered micro units with the same or similar characteristics of each unit,present excellent application potential for various secondary cells due to some merits such as immobilization of active substances,high specific surface area,appropriate pore sizes,easy modification of functional material surface,accommodated huge volume change,enough facilitated transportation for electrons/lithium ions,and special functional groups strongly adsorbing Li PSs.Thus many novel array structured materials are applied to battery for tackling thorny problems mentioned above.In this review,recent progresses and developments on array structured materials applied in LSBs including preparation ways,collaborative structural designs based on array structures,and action mechanism analyses in improving electrochemical performance and safety are summarized.Meanwhile,we also have detailed discussion for array structured materials in LSBs and constructed the structure-function relationships between array structured materials and battery performances.Lastly,some directions and prospects about preparation ways,functional modifications,and practical applications of array structured materials in LSBs are generalized.We hope the review can attract more researchers'attention and bring more studying on array structured materials for other secondary batteries including LSB.展开更多
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 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.
文摘The development of intestinal anastomosis techniques,including hand suturing,stapling,and compression anastomoses,has been a significant advancement in surgical practice.These methods aim to prevent leakage and minimize tissue fibrosis,which can lead to stricture formation.The healing process involves various phases:hemostasis and inflammation,proliferation,and remodeling.Mechanical staplers and sutures can cause inflammation and fibrosis due to the release of profibrotic chemokines.Compression anastomosis devices,including those made of nickel-titanium alloy,offer a minimally invasive option for various surgical challenges and have shown safety and efficacy.However,despite advancements,anastomotic techniques are evaluated based on leakage risk,with complications being a primary concern.Newer devices like Magnamosis use magnetic rings for compression anastomosis,demonstrating greater strength and patency compared to stapling.Magnetic technology is also being explored for other medical treatments.While there are promising results,particularly in animal models,the realworld application in humans is limited,and further research is needed to assess their safety and practicality.
基金The research was supported by the National Natural Science Foundation of China(Grant No.52008307)the Shanghai Sci-ence and Technology Innovation Program(Grant No.19DZ1201004)The third author would like to acknowledge the funding by the China Postdoctoral Science Foundation(Grant No.2023M732670).
文摘The technology of tunnel boring machine(TBM)has been widely applied for underground construction worldwide;however,how to ensure the TBM tunneling process safe and efficient remains a major concern.Advance rate is a key parameter of TBM operation and reflects the TBM-ground interaction,for which a reliable prediction helps optimize the TBM performance.Here,we develop a hybrid neural network model,called Attention-ResNet-LSTM,for accurate prediction of the TBM advance rate.A database including geological properties and TBM operational parameters from the Yangtze River Natural Gas Pipeline Project is used to train and test this deep learning model.The evolutionary polynomial regression method is adopted to aid the selection of input parameters.The results of numerical exper-iments show that our Attention-ResNet-LSTM model outperforms other commonly-used intelligent models with a lower root mean square error and a lower mean absolute percentage error.Further,parametric analyses are conducted to explore the effects of the sequence length of historical data and the model architecture on the prediction accuracy.A correlation analysis between the input and output parameters is also implemented to provide guidance for adjusting relevant TBM operational parameters.The performance of our hybrid intelligent model is demonstrated in a case study of TBM tunneling through a complex ground with variable strata.Finally,data collected from the Baimang River Tunnel Project in Shenzhen of China are used to further test the generalization of our model.The results indicate that,compared to the conventional ResNet-LSTM model,our model has a better predictive capability for scenarios with unknown datasets due to its self-adaptive characteristic.
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Recently,the World Journal of Gastrointestinal Oncology published an article entitled“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”,in which the authors shared their successful experience with complete surgical resection after multidisciplinary conversion therapy.The study by Chu et al demonstrates the great challenges that the advanced hepatocellular carcinoma(HCC)poses to surgical oncology,reveals the complexity of conversion therapy for unresectable HCC,emphasizes the important role of a multidisciplinary management model in conversion therapy,and enriches our understanding of the dynamics of personalized treatment for different patients.At present,conversion therapy is a hot research topic in the treatment of unresectable HCC,which has brought new hope to many patients with moderately advanced HCC.However,there are still many urgent problems to be solved in conversion therapy.Here,we would like to further discuss the advances and challenges of conversion therapy for unresectable HCC with the authors and the general readers.
基金financially supported by the National Natural Science Foundation of China (Nos.51872090 and51772097)the Hebei Natural Science Fund for Distinguished Young Scholar,China (No.E2019209433)+2 种基金the Youth Talent Program of Hebei Provincial Education Department,China (No.BJ2018020)the Natural Science Foundation of Hebei Province,China (No.E2020209151)the Science and Technology Project of Hebei Education Department,China (No.SLRC2019028)。
文摘Zinc-ion batteries(ZIBs) are recognized as potential energy storage devices due to their advantages of low cost, high energy density, and environmental friendliness. However, zinc anodes are subject to unavoidable zinc dendrites, passivation, corrosion, and hydrogen evolution reactions during the charging and discharging of batteries, becoming obstacles to the practical application of ZIBs. Appropriate zinc metal-free anodes provide a higher working potential than metallic zinc anodes, effectively solving the problems of zinc dendrites, hydrogen evolution, and side reactions during the operation of metallic zinc anodes. The improvement in the safety and cycle life of batteries creates conditions for further commercialization of ZIBs. Therefore, this work systematically introduces the research progress of zinc metal-free anodes in “rocking chair” ZIBs. Zinc metal-free anodes are mainly discussed in four categories: transition metal oxides,transition metal sulfides, MXene(two dimensional transition metal carbide) composites, and organic compounds, with discussions on their properties and zinc storage mechanisms. Finally, the outlook for the development of zinc metal-free anodes is proposed. This paper is expected to provide a reference for the further promotion of commercial rechargeable ZIBs.
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.
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supported by the Key-Area Research and Development Program of Guangdong Province(Grant No.2021B0909060002)National Natural Science Foundation of China(Grant Nos.62204219,62204140)+1 种基金Major Program of Natural Science Foundation of Zhejiang Province(Grant No.LDT23F0401)Thanks to Professor Zhang Yishu from Zhejiang University,Professor Gao Xu from Soochow University,and Professor Zhong Shuai from Guangdong Institute of Intelligence Science and Technology for their support。
文摘Embedded memory,which heavily relies on the manufacturing process,has been widely adopted in various industrial applications.As the field of embedded memory continues to evolve,innovative strategies are emerging to enhance performance.Among them,resistive random access memory(RRAM)has gained significant attention due to its numerousadvantages over traditional memory devices,including high speed(<1 ns),high density(4 F^(2)·n^(-1)),high scalability(~nm),and low power consumption(~pJ).This review focuses on the recent progress of embedded RRAM in industrial manufacturing and its potentialapplications.It provides a brief introduction to the concepts and advantages of RRAM,discusses the key factors that impact its industrial manufacturing,and presents the commercial progress driven by cutting-edge nanotechnology,which has been pursued by manysemiconductor giants.Additionally,it highlights the adoption of embedded RRAM in emerging applications within the realm of the Internet of Things and future intelligent computing,with a particular emphasis on its role in neuromorphic computing.Finally,the review discusses thecurrent challenges and provides insights into the prospects of embedded RRAM in the era of big data and artificial intelligence.
基金supported by National Natural Science Foundation of China(52003240)Zhejiang Provincial Natural Science Foundation of China(LQ21B070007)China Postdoctoral Science Foundation(2022M722818).
文摘Realizing fast and continuous generation of reactive oxygen species(ROSs)via iron-based advanced oxidation processes(AOPs)is significant in the environmental and biological fields.However,current AOPs assisted by co-catalysts still suffer from the poor mass/electron transfer and non-durable promotion effect,giving rise to the sluggish Fe^(2+)/Fe^(3+)cycle and low dynamic concentration of Fe^(2+)for ROS production.Herein,we present a three-dimensional(3D)macroscale co-catalyst functionalized with molybdenum disulfide(MoS_(2))to achieve ultra-efficient Fe^(2+)regeneration(equilibrium Fe^(2+)ratio of 82.4%)and remarkable stability(more than 20 cycles)via a circulating flow-through process.Unlike the conventional batch-type reactor,experiments and computational fluid dynamics simulations demonstrate that the optimal utilization of the 3D active area under the flow-through mode,initiated by the convectionenhanced mass/charge transfer for Fe^(2+)reduction and then strengthened by MoS_(2)-induced flow rotation for sufficient reactant mixing,is crucial for oxidant activation and subsequent ROS generation.Strikingly,the flow-through co-catalytic system with superwetting capabilities can even tackle the intricate oily wastewater stabilized by different surfactants without the loss of pollutant degradation efficiency.Our findings highlight an innovative co-catalyst system design to expand the applicability of AOPs based technology,especially in large-scale complex wastewater treatment.
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supported by the research contracts 806/31.4830 and 806/31.5511 between the private company Laboratorio Ortoplus S.L.and the University of Malaga.
文摘Mandibular advancement devices(MADs)are widely used treatments for obstructive sleep apnea.MADs function by advancing the lower jaw to open the upper airway.To increase patient comfort,most patients allow the mouth to be opened.However,not all systems maintain the lower jaw in a forward position during mouth opening,which results in the production of a retrusion that favors the collapse of the upper airway.Furthermore,the kinematic behavior of the mechanism formed by the mandible-device assembly depends on jaw morphology.This means that,during mouth opening,some devices cause lower jaw protrusion in some patients,but cause its retraction in others.In this study,we report the behavior of well-known devices currently on themarket.To do so,we developed a kinematic model of the lower jawdevice assembly.Thismodelwas validated for all devices analyzed using a high-resolution camera system.Our results show that some of the devices analyzed here did not produce the correct behavior during patient mouth opening.
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 grants from the Research Grants Council of the Hong Kong SAR,China(T21-705/20-N and 16210221).
文摘Antibiotic resistant bacteria(ARB)with antibiotic resistance genes(ARGs)can reduce or eliminate the effectiveness of antibiotics and thus threaten human health.The United Nations Environment Programme considers antibiotic resistance the first of six emerging issues of concern.Advanced oxidation processes(AOPs)that combine ultraviolet(UV)irradiation and chemical oxidation(primarily chlorine,hydrogen peroxide,and persulfate)have attracted increasing interest as advanced water and wastewater treatment technologies.These integrated technologies have been reported to significantly elevate the efficiencies of ARB inactivation and ARG degradation compared with direct UV irradiation or chemical oxidation alone due to the generation of multiple reactive species.In this study,the performance and underlying mechanisms of UV/chlorine,UV/hydrogen peroxide,and UV/persulfate processes for controlling ARB and ARGs were reviewed based on recent studies.Factors affecting the process-specific efficiency in controlling ARB and ARGs were discussed,including biotic factors,oxidant dose,UV fluence,pH,and water matrix properties.In addition,the cost-effectiveness of the UV-based AOPs was evaluated using the concept of electrical energy per order.The UV/chlorine process exhibited a higher efficiency with lower energy consumption than other UV-based AOPs in the wastewater matrix,indicating its potential for ARB inactivation and ARG degradation in wastewater treatment.Further studies are required to address the trade-off between toxic byproduct formation and the energy efficiency of the UV/chlorine process in real wastewater to facilitate its optimization and application in the control of ARB and ARGs.
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.
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.
文摘BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.
基金This work was supported by the National Natural Science Foundation of China(52203066,51973157,61904123)the Tianjin Natural Science Foundation(18JCQNJC02900)+3 种基金the National innovation and entrepreneurship training program for college students(202310058007)the Tianjin Municipal college students’innovation and entrepreneurship training program(202310058088)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2018KJ196)the State Key Laboratory of Membrane and Membrane Separation,Tiangong University.
文摘Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely commercial application and development of LSB is mainly hindered by serious“shuttle effect”of lithium polysulfides(Li PSs),slow reaction kinetics,notorious lithium dendrites,etc.In various structures of LSB materials,array structured materials,possessing the composition of ordered micro units with the same or similar characteristics of each unit,present excellent application potential for various secondary cells due to some merits such as immobilization of active substances,high specific surface area,appropriate pore sizes,easy modification of functional material surface,accommodated huge volume change,enough facilitated transportation for electrons/lithium ions,and special functional groups strongly adsorbing Li PSs.Thus many novel array structured materials are applied to battery for tackling thorny problems mentioned above.In this review,recent progresses and developments on array structured materials applied in LSBs including preparation ways,collaborative structural designs based on array structures,and action mechanism analyses in improving electrochemical performance and safety are summarized.Meanwhile,we also have detailed discussion for array structured materials in LSBs and constructed the structure-function relationships between array structured materials and battery performances.Lastly,some directions and prospects about preparation ways,functional modifications,and practical applications of array structured materials in LSBs are generalized.We hope the review can attract more researchers'attention and bring more studying on array structured materials for other secondary batteries including LSB.