Recent Progress in Reinforcement Learning and Adaptive Dynamic Programming for Advanced Control Applications

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.

基于PLCSIM Advanced和Simulink的自动化生产线仿真实训平台设计

为解决自动化生产线实训线下课程实验硬件套数不足、实验时长和场地受限等问题,提升教学质量,设计了一种基于PLCSIM Advanced和Simulink的自动化生产线仿真实训平台。该仿真平台以实训设备为依托,使用Simulink搭建被控对象仿真模型,在PLCSIM Advanced仿真控制器中编写控制算法,通过应用程序接口(application programming interface,API)通信实现对象模型与控制器间数据的实时交换和仿真。以纸张张力控制设备为例,介绍了仿真实训平台搭建和实施过程。实践教学表明,该仿真平台提高了自动化生产线实训课程的教学成效,激发了学生实践学习的兴趣,提升了学生发现、解决复杂工程问题的能力,让学生深刻体会到团队合作和有效沟通的重要性。

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

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.

Design and analysis of an advanced thermal management system for the solar close observations and proximity experiments spacecraft

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.

Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma:a real-world study

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.

Mass Transfer-Promoted Fe^(2+)/Fe^(3+)Circulation Steered by 3D Flow-Through Co-Catalyst System Toward Sustainable Advanced Oxidation Processes

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.

Comprehensive analysis of advanced glycation end-products in commonly consumed foods:presenting a database for dietary AGEs and associated exposure assessment

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.

A Comprehensive Survey on Advanced Persistent Threat (APT) Detection Techniques

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.

UV-Based Advanced Oxidation Processes for Antibiotic Resistance Control: Efficiency, Influencing Factors, and Energy Consumption

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.

Diet with high content of advanced glycation end products induces oxidative stress damage and systemic inflammation in experimental mice: protective effect of peanut skin procyanidins

Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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).

Design,preparation,application of advanced array structured materials and their action mechanism analyses for high performance lithium-sulfur batteries

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.

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

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.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

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.

Survey on hospice care attitude of family members of advanced cancer patients at different ages

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.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)cancer.AIM To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative resection.METHODS This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018.The impact of CCRT on advanced AoV cancer was analyzed.RESULTS The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,respectively.Lymphovas-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis.Compared to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio.CONCLUSION Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer.These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model

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.

Bioengineering breakthroughs:The impact of stem cell models on advanced therapy medicinal product development

The burgeoning field of bioengineering has witnessed significant strides due to the advent of stem cell models,particularly in their application in advanced therapy medicinal products(ATMPs).In this review,we examine the multifaceted impact of these developments,emphasizing the potential of stem cell models to enhance the sophistication of ATMPs and to offer alternatives to animal testing.Stem cell-derived tissues are particularly promising because they can reshape the preclinical landscape by providing more physiologically relevant and ethically sound platforms for drug screening and disease modelling.We also discuss the critical challenges of reproducibility and accuracy in measurements to ensure the integrity and utility of stem cell models in research and application.Moreover,this review highlights the imperative of stem cell models to align with regulatory standards,ensuring using stem cells in ATMPs translates into safe and effective clinical therapies.With regulatory approval serving as a gateway to clinical adoption,the collaborative efforts between scientists and regulators are vital for the progression of stem cell applications from bench to bedside.We advocate for a balanced approach that nurtures innovation within the framework of rigorous validation and regulatory compliance,ensuring that stem cell-base solutions are maximized to promote public trust and patient health in ATMPs.