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
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
Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures ha...Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.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
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
BACKGROUND Gastric cancer(GC)is a major health concern worldwide.Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different...BACKGROUND Gastric cancer(GC)is a major health concern worldwide.Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different in each individual.Chemotherapy can be administered both pre-and postoperatively,but a multidisciplinary approach is preferred when possible.This is particularly relevant for locally advanced GC(LAGC),as neoadjuvant chemotherapy(NAT)could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent.Even though the recent progress has been impressive,European and International guidelines are still controversial,thus attenuating the need for a more standardized approach in the management of locally advanced cancer.AIM To investigate the effects of NAT on the overall survival(OS),the disease-free survival(DFS),the morbidity and the mortality of patients with LAGC in comparison to upfront surgery(US).METHODS For this systematic review,a literature search was conducted between November and February 2023 in PubMed,Cochrane Library and clinicaltrials.gov for studies including patients with LAGC.Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews.RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review.Patients were separated into two groups;one receiving NAT before the gastrectomy(NAT group)and the other undergoing upfront surgery(US group).The OS ranged from 41.6%to 74.2%in the NAT group and from 30.9%to 74%in the US group.The DFS was also longer in the NAT group and reached up to 80%in certain patients.The complications related to the chemotherapy or the surgery ranged from 6.4%to 38.1%in the NAT group and from 5%to 40.5%in the US group.Even though in most of the studies the morbidity was lower in the NAT group,a general conclusion could not be drawn as it seems to depend on multiple factors.Finally,regarding the mortality,the reported rate was higher and up to 5.3%in the US group.CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates.However,patients with different clinicopathological features respond differently to chemotherapy,therefore currently the treatment plan should be individualized in order to achieve optimal results.展开更多
Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to ...Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to summarize reliable evidence for the preoperative neoadjuvant immunotherapy of rlaEc by analyzing all the published clinical trials on the ICIs as the neoadjuvant therapy for rlaEC.Methods:PubMed,Cochrane Library,Embase and ClinicalTrials.gov were searched from inception until June 1st,2023,for available reports to perform a meta-analysis.The primary endpoints were RO resection,objective response rate(ORR),pathological complete response(pCR)and major pathological response(MPR),as well as treatment-related adverse events(AEs)and postoperative complications.The Stata 14.0 software was employed to estimate pooled effect size.Results:A total of 18 single-arm clinical trials involving 625 patients met the inclusion criteria.Meta-analysis showed that,among these patients with rlaEC,the pooled R0 resection rate was 97.0%(95%CI:94.0%-99.0%),the p0oled ORR was 70.0%(95%CI:64.0%-76.0%),the p0oled pCR and MPR rate were 34.0%(95%CI:29.0%-39.0%)and 56.0%(95%CI:47.0%-65.0%)respectively.The incidence of main treatment-related AEs and postoperative complications was about 6%-45% and 8%-19% respectively.Conclusions:Patients with rlaEC were tolerated to neoadjuvant immunotherapy and it might be beneficial to improve efficacy.But this meta-analysis had limitations and the conclusions still needed to be validated by more rigorous phase II randomized controlled clinical trials.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
We are privileged to be invited by the Honorary Editor-in-Chief,Professor Qihu Qian,Editor-in-Chief,Professor Xia-Ting Feng,and the editorial staff of the Journal of Rock Mechanics and Geotechnical Engineering(JRMGE),...We are privileged to be invited by the Honorary Editor-in-Chief,Professor Qihu Qian,Editor-in-Chief,Professor Xia-Ting Feng,and the editorial staff of the Journal of Rock Mechanics and Geotechnical Engineering(JRMGE),to serve as Guest Editors for this Special Issue(SI).In literature there have been new advancements in monitoring techniques,advanced numerical modelling,optimization algorithms,artificial intelligence and data science introduced for slope engineering.The newly proposed approaches show great potential for improving slope design,construction,and risk assessment.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
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
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.
文摘Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.
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.
文摘BACKGROUND Gastric cancer(GC)is a major health concern worldwide.Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different in each individual.Chemotherapy can be administered both pre-and postoperatively,but a multidisciplinary approach is preferred when possible.This is particularly relevant for locally advanced GC(LAGC),as neoadjuvant chemotherapy(NAT)could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent.Even though the recent progress has been impressive,European and International guidelines are still controversial,thus attenuating the need for a more standardized approach in the management of locally advanced cancer.AIM To investigate the effects of NAT on the overall survival(OS),the disease-free survival(DFS),the morbidity and the mortality of patients with LAGC in comparison to upfront surgery(US).METHODS For this systematic review,a literature search was conducted between November and February 2023 in PubMed,Cochrane Library and clinicaltrials.gov for studies including patients with LAGC.Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews.RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review.Patients were separated into two groups;one receiving NAT before the gastrectomy(NAT group)and the other undergoing upfront surgery(US group).The OS ranged from 41.6%to 74.2%in the NAT group and from 30.9%to 74%in the US group.The DFS was also longer in the NAT group and reached up to 80%in certain patients.The complications related to the chemotherapy or the surgery ranged from 6.4%to 38.1%in the NAT group and from 5%to 40.5%in the US group.Even though in most of the studies the morbidity was lower in the NAT group,a general conclusion could not be drawn as it seems to depend on multiple factors.Finally,regarding the mortality,the reported rate was higher and up to 5.3%in the US group.CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates.However,patients with different clinicopathological features respond differently to chemotherapy,therefore currently the treatment plan should be individualized in order to achieve optimal results.
基金supported by funded by National Nature Science Foundation of China,grant number 82074315.
文摘Background:Immune checkpoint inhibitors(ICIs)as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma(rlaEC)remains challenging given the poor reports of efficacy and safety.This study aimed to summarize reliable evidence for the preoperative neoadjuvant immunotherapy of rlaEc by analyzing all the published clinical trials on the ICIs as the neoadjuvant therapy for rlaEC.Methods:PubMed,Cochrane Library,Embase and ClinicalTrials.gov were searched from inception until June 1st,2023,for available reports to perform a meta-analysis.The primary endpoints were RO resection,objective response rate(ORR),pathological complete response(pCR)and major pathological response(MPR),as well as treatment-related adverse events(AEs)and postoperative complications.The Stata 14.0 software was employed to estimate pooled effect size.Results:A total of 18 single-arm clinical trials involving 625 patients met the inclusion criteria.Meta-analysis showed that,among these patients with rlaEC,the pooled R0 resection rate was 97.0%(95%CI:94.0%-99.0%),the p0oled ORR was 70.0%(95%CI:64.0%-76.0%),the p0oled pCR and MPR rate were 34.0%(95%CI:29.0%-39.0%)and 56.0%(95%CI:47.0%-65.0%)respectively.The incidence of main treatment-related AEs and postoperative complications was about 6%-45% and 8%-19% respectively.Conclusions:Patients with rlaEC were tolerated to neoadjuvant immunotherapy and it might be beneficial to improve efficacy.But this meta-analysis had limitations and the conclusions still needed to be validated by more rigorous phase II randomized controlled clinical trials.
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We are privileged to be invited by the Honorary Editor-in-Chief,Professor Qihu Qian,Editor-in-Chief,Professor Xia-Ting Feng,and the editorial staff of the Journal of Rock Mechanics and Geotechnical Engineering(JRMGE),to serve as Guest Editors for this Special Issue(SI).In literature there have been new advancements in monitoring techniques,advanced numerical modelling,optimization algorithms,artificial intelligence and data science introduced for slope engineering.The newly proposed approaches show great potential for improving slope design,construction,and risk assessment.
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.
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.