This study aims to address the problems existing in the ideological and political education of postgraduate students,and combines the implementation of the mentor responsibility system to explore the role orientation,...This study aims to address the problems existing in the ideological and political education of postgraduate students,and combines the implementation of the mentor responsibility system to explore the role orientation,work content,and practical effects of mentors in the ideological and political education of postgraduate students.Through questionnaire surveys,interviews,and other research methods,the current situation of ideological and political education of postgraduate students under the mentor responsibility system is analyzed,and corresponding optimization strategies are proposed.展开更多
This study analyzed the impact of land-based contaminants and tertiary industrial structure on economic development in the selected Bohai Bay area,China.Based on panel data spanning 2011-2020,a vector autoregressive(V...This study analyzed the impact of land-based contaminants and tertiary industrial structure on economic development in the selected Bohai Bay area,China.Based on panel data spanning 2011-2020,a vector autoregressive(VAR)model is used to analyze and forecast the short-run and long-run relationships between three industrial structures,pollutant discharge,and economic development.The results showed that the environmental index had a long-term cointegration relationship with the industrial structure economic index.Per capital chemical oxygen demand(PCOD)and per capita ammonia nitrogen(PNH_(3)N)had a positive impact on delta per capita GDP(dPGDP),while per capita solid waste(PSW),the secondary industry rate(SIR)and delta tertiary industry(dTIR)had a negative impact on dPGDP.The VAR model under this coupling system had stability and credibility.The impulse response results showed that the short-term effect of the coupling system on dPGDP was basically consistent with the Granger causality test results.In addition,variance decomposition was used in this study to predict the long-term impact of the coupling system in the next ten periods(i.e.,ten years).It was found that dTIR had a great impact on dPGDP,with a contribution rate as high as 74.35%in the tenth period,followed by the contribution rate of PCOD up to 3.94%,while the long-term contribution rates of PSW,SIR and PNH3N were all less than 1%.The results show that the government should support the development of the tertiary industry to maintain the vitality of economic development and prevent environmental deterioration.展开更多
Petroleum hydrocarbon pollution is a global concern,particularly in coastal environments.Polycyclic aromatic hydrocarbons(PAHs) are regarded as the most toxic components of petroleum hydrocarbons.In this study,the bio...Petroleum hydrocarbon pollution is a global concern,particularly in coastal environments.Polycyclic aromatic hydrocarbons(PAHs) are regarded as the most toxic components of petroleum hydrocarbons.In this study,the biomonitoring and ranking effects of petroleum hydrocarbons and PAHs on the marine fish model Oryzias melastigma embryos were determined in the Jiulong River Estuary(JRE) and its adjacent waters in China.The results showed that the levels of petroleum hydrocarbons from almost all sites met the primary standard for marine seawater quality,and the concentrations of the 16 priority PAHs in the surface seawater were lower compared with those in other coastal areas worldwide.A new fish expert system based on the embryotoxicity of O.melastigma(OME-FES) was developed and applied in the field to evaluate the biological effects of petroleum hydrocarbons and PAHs.The selected physiological index and molecular indicators in OME-FES were appropriate biomarkers for indicating the harmful effects of petroleum hydrocarbons and PAHs.The outcome of OME-FES revealed that the biological effect levels of the sampling sites ranged from level Ⅰ(no stress) to level Ⅲ(medium stress),which is further corroborated by the findings of nested analysis of variance(ANOVA) models.Our results suggest that the OME-FES is an effective tool for evaluating and ranking the biological effects of marine petroleum hydrocarbons and PAHs.This method may also be applied to evaluate other marine pollutants based on its framework.展开更多
The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfo...The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.展开更多
Fire warning is vital to human life,economy and ecology.However,the development of effective warning systems faces great challenges of fast response,adjustable threshold and remote detecting.Here,we propose an intelli...Fire warning is vital to human life,economy and ecology.However,the development of effective warning systems faces great challenges of fast response,adjustable threshold and remote detecting.Here,we propose an intelligent self-powered remote IoT fire warning system,by employing single-walled carbon nanotube/titanium carbide thermoelectric composite films.The flexible films,prepared by a convenient solution mixing,display p-type characteristic with excellent high-temperature stability,flame retardancy and TE(power factor of 239.7±15.8μW m^(-1) K^(-2))performances.The comprehensive morphology and structural analyses shed light on the underlying mechanisms.And the assembled TE devices(TEDs)exhibit fast fire warning with adjustable warning threshold voltages(1–10 mV).Excitingly,an ultrafast fire warning response time of~0.1 s at 1 mV threshold voltage is achieved,rivaling many state-of-the-art systems.Furthermore,TE fire warning systems reveal outstanding stability after 50 repeated cycles and desired durability even undergoing 180 days of air exposure.Finally,a TED-based wireless intelligent fire warning system has been developed by coupling an amplifier,analogto-digital converter and Bluetooth module.By combining TE characteristics,high-temperature stability and flame retardancy with wireless IoT signal transmission,TE-based hybrid system developed here is promising for next-generation self-powered remote IoT fire warning applications.展开更多
Human agency has become increasingly limited in complex systems with increasingly automated decision-making capabilities.For instance,human occupants are passengers and do not have direct vehicle control in fully auto...Human agency has become increasingly limited in complex systems with increasingly automated decision-making capabilities.For instance,human occupants are passengers and do not have direct vehicle control in fully automated cars(i.e.,driverless cars).An interesting question is whether users are responsible for the accidents of these cars.Normative ethical and legal analyses frequently argue that individuals should not bear responsibility for harm beyond their control.Here,we consider human judgment of responsibility for accidents involving fully automated cars through three studies with seven experiments(N=2668).We compared the responsibility attributed to the occupants in three conditions:an owner in his private fully automated car,a passenger in a driverless robotaxi,and a passenger in a conventional taxi,where none of these three occupants have direct vehicle control over the involved vehicles that cause identical pedestrian injury.In contrast to normative analyses,we show that the occupants of driverless cars(private cars and robotaxis)are attributed more responsibility than conventional taxi passengers.This dilemma is robust across different contexts(e.g.,participants from China vs the Republic of Korea,participants with first-vs third-person perspectives,and occupant presence vs absence).Furthermore,we observe that this is not due to the perception that these occupants have greater control over driving but because they are more expected to foresee the potential consequences of using driverless cars.Our findings suggest that when driverless vehicles(private cars and taxis)cause harm,their users may face more social pressure,which public discourse and legal regulations should manage appropriately.展开更多
This paper aims to analyze the present conditions of the social responsibility ecosystem in online audiovisual enterprises in the digital age. It focuses on the governance of social responsibility in these enterprises...This paper aims to analyze the present conditions of the social responsibility ecosystem in online audiovisual enterprises in the digital age. It focuses on the governance of social responsibility in these enterprises and conducts an in-depth analysis of the problems and influencing factors related to the social responsibility aberrations of online audiovisual enterprises. Drawing upon social responsibility theory and collaborative governance theory, this research constructs a social responsibility guidance and governance system guided by the public, supported by the voluntary fulfillment of responsibilities by online audiovisual enterprises, and based on the collaborative participation of diverse stakeholders. It explores and optimizes the implementation pathways of this system, providing theoretical support and practical guidance for promoting the sustainable development of online audiovisual enterprises. Furthermore, it aims to contribute to the creation of a harmonious Internet ecosystem.展开更多
BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic signific...BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.展开更多
A complete road-soft ground model is established in this paper to study the dynamic responses caused by vehicle loads and/or daily temperature variation.A dynamic thermo-elastic model is applied to capturing the behav...A complete road-soft ground model is established in this paper to study the dynamic responses caused by vehicle loads and/or daily temperature variation.A dynamic thermo-elastic model is applied to capturing the behavior of the rigid pavement,the base course,and the subgrade,while the soft ground is characterized using a dynamic thermo-poroelastic model.Solutions to the road-soft ground system are derived in the Laplace-Hankel transform domain.The time domain solutions are obtained using an integration approach.The temperature,thermal stress,pore water pressure,and displacement responses caused by the vehicle load and the daily temperature variation are presented.Results show that obvious temperature change mainly exists within 0.3 m of the road when subjected to the daily temperature variation,whereas the stress responses can still be found in deeper places because of the thermal swelling/shrinkage deformation within the upper road structures.Moreover,it is important to consider the coupling effects of the vehicle load and the daily temperature variation when calculating the dynamic responses inside the road-soft ground system.展开更多
With the increasing penetration of wind and solar energies,the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems.A source-grid-load-storage co...With the increasing penetration of wind and solar energies,the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems.A source-grid-load-storage coordinated expansion planning model based on stochastic programming was proposed to suppress the impact of wind and solar energy fluctuations.Multiple types of system components,including demand response service entities,converter stations,DC transmission systems,cascade hydropower stations,and other traditional components,have been extensively modeled.Moreover,energy storage systems are considered to improve the accommodation level of renewable energy and alleviate the influence of intermittence.Demand-response service entities from the load side are used to reduce and move the demand during peak load periods.The uncertainties in wind,solar energy,and loads were simulated using stochastic programming.Finally,the effectiveness of the proposed model is verified through numerical simulations.展开更多
With the rise of remote work and the digital industry,advanced cyberattacks have become more diverse and complex in terms of attack types and characteristics,rendering them difficult to detect with conventional intrus...With the rise of remote work and the digital industry,advanced cyberattacks have become more diverse and complex in terms of attack types and characteristics,rendering them difficult to detect with conventional intrusion detection methods.Signature-based intrusion detection methods can be used to detect attacks;however,they cannot detect new malware.Endpoint detection and response(EDR)tools are attracting attention as a means of detecting attacks on endpoints in real-time to overcome the limitations of signature-based intrusion detection techniques.However,EDR tools are restricted by the continuous generation of unnecessary logs,resulting in poor detection performance and memory efficiency.Machine learning-based intrusion detection techniques for responding to advanced cyberattacks are memory intensive,using numerous features;they lack optimal feature selection for each attack type.To overcome these limitations,this study proposes a memory-efficient intrusion detection approach incorporating multi-binary classifiers using optimal feature selection.The proposed model detects multiple types of malicious attacks using parallel binary classifiers with optimal features for each attack type.The experimental results showed a 2.95%accuracy improvement and an 88.05%memory reduction using only six features compared to a model with 18 features.Furthermore,compared to a conventional multi-classification model with simple feature selection based on permutation importance,the accuracy improved by 11.67%and the memory usage decreased by 44.87%.The proposed scheme demonstrates that effective intrusion detection is achievable with minimal features,making it suitable for memory-limited mobile and Internet of Things devices.展开更多
BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent addit...BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.展开更多
Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer ...Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Hot dry rock(HDR)is rich in reserve,widely distributed,green,low-carbon,and has broad development potential and prospects.In this paper,a distributionally robust optimization(DRO)scheduling model for a regionally inte...Hot dry rock(HDR)is rich in reserve,widely distributed,green,low-carbon,and has broad development potential and prospects.In this paper,a distributionally robust optimization(DRO)scheduling model for a regionally integrated energy system(RIES)considering HDR co-generation is proposed.First,the HDR-enhanced geothermal system(HDR-EGS)is introduced into the RIES.HDR-EGS realizes the thermoelectric decoupling of combined heat and power(CHP)through coordinated operation with the regional power grid and the regional heat grid,which enhances the system wind power(WP)feed-in space.Secondly,peak-hour loads are shifted using price demand response guidance in the context of time-of-day pricing.Finally,the optimization objective is established to minimize the total cost in the RIES scheduling cycle and construct a DRO scheduling model for RIES with HDR-EGS.By simulating a real small-scale RIES,the results show that HDR-EGS can effectively promote WP consumption and reduce the operating cost of the system.展开更多
BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomark...BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma(dCCA)who underwent pancreat-oduodenectomy(PD).METHODS This single-center study included 216 patients with dCCA after PD between January 1,2011,and December 31,2022.The individuals were categorized into two sets based on their systemic inflammatory response index(SIRI)levels:A low SIRI group(SIRI<1.5,n=123)and a high SIRI group(SIRI≥1.5,n=93).Inflam-matory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves.Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival(OS)and recurrence-free survival(RFS).RESULTS The study included a total of 216 patients,with 58.3%being male and a mean age of 65.6±9.6 years.123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA.SIRI had an area under the curve value of 0.674 for diagnosing dCCA,showing better performance than other inflammatory biomarkers.Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD,leading to lower OS[hazard ratios(HR)=1.868,P=0.006]and RFS(HR=0.949,P<0.001).Additionally,survival analysis indicated a significantly better prognosis for patients in the low SIRI group(P<0.001).CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.展开更多
BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascer...BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.展开更多
Digital integration within healthcare systems exacerbates their vulnerability to sophisticated ransomware threats, leading to severe operational disruptions and data breaches. Current defenses are typically categorize...Digital integration within healthcare systems exacerbates their vulnerability to sophisticated ransomware threats, leading to severe operational disruptions and data breaches. Current defenses are typically categorized into active and passive measures that struggle to achieve comprehensive threat mitigation and often lack real-time response effectiveness. This paper presents an innovative ransomware defense system, ERAD, designed for healthcare environments that apply the MITRE ATT&CK Matrix to coordinate dynamic, stage-specific countermeasures throughout the ransomware attack lifecycle. By systematically identifying and addressing threats based on indicators of compromise (IOCs), the proposed system proactively disrupts the attack chain before serious damage occurs. Validation is provided through a detailed analysis of a system deployment against LockBit 3.0 ransomware, illustrating significant enhancements in mitigating the impact of the attack, reducing the cost of recovery, and strengthening the cybersecurity framework of healthcare organizations, but also applicable to other non-health sectors of the business world.展开更多
Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune ...Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.展开更多
BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AI...BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.展开更多
基金Chang’an University Graduate Student Ideological and Political Education Innovation Demonstration Pro-ject(No.300103740013)Education Science Research Project of China Association of Transportation Education(No.JT2022YB222)+1 种基金Research Project on Education and Teaching Reform at Chang’an Dublin International College of Transpor-tation at Chang’an University(No.CDIC-JG-200301)Construction Project for Continuous Improvement of National First-Class Courses on Interchangeability and Measurement Technology(No.300103230119)。
文摘This study aims to address the problems existing in the ideological and political education of postgraduate students,and combines the implementation of the mentor responsibility system to explore the role orientation,work content,and practical effects of mentors in the ideological and political education of postgraduate students.Through questionnaire surveys,interviews,and other research methods,the current situation of ideological and political education of postgraduate students under the mentor responsibility system is analyzed,and corresponding optimization strategies are proposed.
基金supported by the research funds for Coupling Research on Industrial Upgrade and Environmental Management in the Bohai Rim-Technique,methodology,and Environmental Economic Policies(No.42076221).
文摘This study analyzed the impact of land-based contaminants and tertiary industrial structure on economic development in the selected Bohai Bay area,China.Based on panel data spanning 2011-2020,a vector autoregressive(VAR)model is used to analyze and forecast the short-run and long-run relationships between three industrial structures,pollutant discharge,and economic development.The results showed that the environmental index had a long-term cointegration relationship with the industrial structure economic index.Per capital chemical oxygen demand(PCOD)and per capita ammonia nitrogen(PNH_(3)N)had a positive impact on delta per capita GDP(dPGDP),while per capita solid waste(PSW),the secondary industry rate(SIR)and delta tertiary industry(dTIR)had a negative impact on dPGDP.The VAR model under this coupling system had stability and credibility.The impulse response results showed that the short-term effect of the coupling system on dPGDP was basically consistent with the Granger causality test results.In addition,variance decomposition was used in this study to predict the long-term impact of the coupling system in the next ten periods(i.e.,ten years).It was found that dTIR had a great impact on dPGDP,with a contribution rate as high as 74.35%in the tenth period,followed by the contribution rate of PCOD up to 3.94%,while the long-term contribution rates of PSW,SIR and PNH3N were all less than 1%.The results show that the government should support the development of the tertiary industry to maintain the vitality of economic development and prevent environmental deterioration.
基金The Scientific Research Foundation of the Third Institute of Oceanography,Ministry of Natural Resources under contract Nos 2020014 and 2020017the National Natural Science Foundation of China under contract No.41977211the National Program on Global Change and Air-Sea Interaction under contract No.GASI-02-SCS-YDsum。
文摘Petroleum hydrocarbon pollution is a global concern,particularly in coastal environments.Polycyclic aromatic hydrocarbons(PAHs) are regarded as the most toxic components of petroleum hydrocarbons.In this study,the biomonitoring and ranking effects of petroleum hydrocarbons and PAHs on the marine fish model Oryzias melastigma embryos were determined in the Jiulong River Estuary(JRE) and its adjacent waters in China.The results showed that the levels of petroleum hydrocarbons from almost all sites met the primary standard for marine seawater quality,and the concentrations of the 16 priority PAHs in the surface seawater were lower compared with those in other coastal areas worldwide.A new fish expert system based on the embryotoxicity of O.melastigma(OME-FES) was developed and applied in the field to evaluate the biological effects of petroleum hydrocarbons and PAHs.The selected physiological index and molecular indicators in OME-FES were appropriate biomarkers for indicating the harmful effects of petroleum hydrocarbons and PAHs.The outcome of OME-FES revealed that the biological effect levels of the sampling sites ranged from level Ⅰ(no stress) to level Ⅲ(medium stress),which is further corroborated by the findings of nested analysis of variance(ANOVA) models.Our results suggest that the OME-FES is an effective tool for evaluating and ranking the biological effects of marine petroleum hydrocarbons and PAHs.This method may also be applied to evaluate other marine pollutants based on its framework.
基金supported by grants from the National Institutes of Health,No.NS105689(to WL)the Department of Defense through the Multiple Sclerosis Research Program,No.W81XWH-22-1-0757(to WL).
文摘The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2022A1515110296,2022A1515110432)the Shenzhen Science and Technology Program(No.20231120171032001,20231122125728001).
文摘Fire warning is vital to human life,economy and ecology.However,the development of effective warning systems faces great challenges of fast response,adjustable threshold and remote detecting.Here,we propose an intelligent self-powered remote IoT fire warning system,by employing single-walled carbon nanotube/titanium carbide thermoelectric composite films.The flexible films,prepared by a convenient solution mixing,display p-type characteristic with excellent high-temperature stability,flame retardancy and TE(power factor of 239.7±15.8μW m^(-1) K^(-2))performances.The comprehensive morphology and structural analyses shed light on the underlying mechanisms.And the assembled TE devices(TEDs)exhibit fast fire warning with adjustable warning threshold voltages(1–10 mV).Excitingly,an ultrafast fire warning response time of~0.1 s at 1 mV threshold voltage is achieved,rivaling many state-of-the-art systems.Furthermore,TE fire warning systems reveal outstanding stability after 50 repeated cycles and desired durability even undergoing 180 days of air exposure.Finally,a TED-based wireless intelligent fire warning system has been developed by coupling an amplifier,analogto-digital converter and Bluetooth module.By combining TE characteristics,high-temperature stability and flame retardancy with wireless IoT signal transmission,TE-based hybrid system developed here is promising for next-generation self-powered remote IoT fire warning applications.
基金supported by the National Natural Science Foundation of China(72071143)。
文摘Human agency has become increasingly limited in complex systems with increasingly automated decision-making capabilities.For instance,human occupants are passengers and do not have direct vehicle control in fully automated cars(i.e.,driverless cars).An interesting question is whether users are responsible for the accidents of these cars.Normative ethical and legal analyses frequently argue that individuals should not bear responsibility for harm beyond their control.Here,we consider human judgment of responsibility for accidents involving fully automated cars through three studies with seven experiments(N=2668).We compared the responsibility attributed to the occupants in three conditions:an owner in his private fully automated car,a passenger in a driverless robotaxi,and a passenger in a conventional taxi,where none of these three occupants have direct vehicle control over the involved vehicles that cause identical pedestrian injury.In contrast to normative analyses,we show that the occupants of driverless cars(private cars and robotaxis)are attributed more responsibility than conventional taxi passengers.This dilemma is robust across different contexts(e.g.,participants from China vs the Republic of Korea,participants with first-vs third-person perspectives,and occupant presence vs absence).Furthermore,we observe that this is not due to the perception that these occupants have greater control over driving but because they are more expected to foresee the potential consequences of using driverless cars.Our findings suggest that when driverless vehicles(private cars and taxis)cause harm,their users may face more social pressure,which public discourse and legal regulations should manage appropriately.
文摘This paper aims to analyze the present conditions of the social responsibility ecosystem in online audiovisual enterprises in the digital age. It focuses on the governance of social responsibility in these enterprises and conducts an in-depth analysis of the problems and influencing factors related to the social responsibility aberrations of online audiovisual enterprises. Drawing upon social responsibility theory and collaborative governance theory, this research constructs a social responsibility guidance and governance system guided by the public, supported by the voluntary fulfillment of responsibilities by online audiovisual enterprises, and based on the collaborative participation of diverse stakeholders. It explores and optimizes the implementation pathways of this system, providing theoretical support and practical guidance for promoting the sustainable development of online audiovisual enterprises. Furthermore, it aims to contribute to the creation of a harmonious Internet ecosystem.
文摘BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.
基金funding support from the National Natural Science Foundation of China(Grant Nos.42077262 and 42077261).
文摘A complete road-soft ground model is established in this paper to study the dynamic responses caused by vehicle loads and/or daily temperature variation.A dynamic thermo-elastic model is applied to capturing the behavior of the rigid pavement,the base course,and the subgrade,while the soft ground is characterized using a dynamic thermo-poroelastic model.Solutions to the road-soft ground system are derived in the Laplace-Hankel transform domain.The time domain solutions are obtained using an integration approach.The temperature,thermal stress,pore water pressure,and displacement responses caused by the vehicle load and the daily temperature variation are presented.Results show that obvious temperature change mainly exists within 0.3 m of the road when subjected to the daily temperature variation,whereas the stress responses can still be found in deeper places because of the thermal swelling/shrinkage deformation within the upper road structures.Moreover,it is important to consider the coupling effects of the vehicle load and the daily temperature variation when calculating the dynamic responses inside the road-soft ground system.
基金supported by Science and Technology Project of SGCC(SGSW0000FZGHBJS2200070)。
文摘With the increasing penetration of wind and solar energies,the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems.A source-grid-load-storage coordinated expansion planning model based on stochastic programming was proposed to suppress the impact of wind and solar energy fluctuations.Multiple types of system components,including demand response service entities,converter stations,DC transmission systems,cascade hydropower stations,and other traditional components,have been extensively modeled.Moreover,energy storage systems are considered to improve the accommodation level of renewable energy and alleviate the influence of intermittence.Demand-response service entities from the load side are used to reduce and move the demand during peak load periods.The uncertainties in wind,solar energy,and loads were simulated using stochastic programming.Finally,the effectiveness of the proposed model is verified through numerical simulations.
基金supported by MOTIE under Training Industrial Security Specialist for High-Tech Industry(RS-2024-00415520)supervised by the Korea Institute for Advancement of Technology(KIAT),and by MSIT under the ICT Challenge and Advanced Network of HRD(ICAN)Program(No.IITP-2022-RS-2022-00156310)supervised by the Institute of Information&Communication Technology Planning&Evaluation(IITP)。
文摘With the rise of remote work and the digital industry,advanced cyberattacks have become more diverse and complex in terms of attack types and characteristics,rendering them difficult to detect with conventional intrusion detection methods.Signature-based intrusion detection methods can be used to detect attacks;however,they cannot detect new malware.Endpoint detection and response(EDR)tools are attracting attention as a means of detecting attacks on endpoints in real-time to overcome the limitations of signature-based intrusion detection techniques.However,EDR tools are restricted by the continuous generation of unnecessary logs,resulting in poor detection performance and memory efficiency.Machine learning-based intrusion detection techniques for responding to advanced cyberattacks are memory intensive,using numerous features;they lack optimal feature selection for each attack type.To overcome these limitations,this study proposes a memory-efficient intrusion detection approach incorporating multi-binary classifiers using optimal feature selection.The proposed model detects multiple types of malicious attacks using parallel binary classifiers with optimal features for each attack type.The experimental results showed a 2.95%accuracy improvement and an 88.05%memory reduction using only six features compared to a model with 18 features.Furthermore,compared to a conventional multi-classification model with simple feature selection based on permutation importance,the accuracy improved by 11.67%and the memory usage decreased by 44.87%.The proposed scheme demonstrates that effective intrusion detection is achievable with minimal features,making it suitable for memory-limited mobile and Internet of Things devices.
文摘BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.
基金National Natural Science Foundation of China under Grant No.51878508。
文摘Cemented and mechanically clamped types of end fittings(fitting-C and fitting-M)are commonly used in transformer bushings.During the Luding Ms 6.8 earthquake that occurred in China on September 5,2022,all transformer bushings with the two types of end fittings in a 500 kV substation were damaged.Post-earthquake field investigations were conducted,and the failures of the two types of bushings were compared.Two elementary simulation models of the transformer-bushing systems were developed to simulate the engineering failures,and further compute their seismic responses for comparison.The results indicate that the hitch lugs of the connection flange are structurally harmful to seismic resistance.Fitting-M can decrease the bending stiffness of the bushing due to the flexible sealing rubber gasket.Since it provides a more flexible connection that dissipates energy,the peak accelerations and relative displacements at the top of the bushing are significantly lower than those of the bushing with fitting-C.Compared with fitting-C,fitting-M transfers the high-stress areas from the connection flange to the root of the porcelain,so the latter becomes the most vulnerable component.Fitting-M increases the failure risk of the low-strength porcelain,indicating the unsuitability of applying it in high-intensity fortification regions.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金King Saud University for funding this research through the Researchers Supporting Program Number(RSPD2024R704),King Saud University,Riyadh,Saudi Arabia.
文摘Hot dry rock(HDR)is rich in reserve,widely distributed,green,low-carbon,and has broad development potential and prospects.In this paper,a distributionally robust optimization(DRO)scheduling model for a regionally integrated energy system(RIES)considering HDR co-generation is proposed.First,the HDR-enhanced geothermal system(HDR-EGS)is introduced into the RIES.HDR-EGS realizes the thermoelectric decoupling of combined heat and power(CHP)through coordinated operation with the regional power grid and the regional heat grid,which enhances the system wind power(WP)feed-in space.Secondly,peak-hour loads are shifted using price demand response guidance in the context of time-of-day pricing.Finally,the optimization objective is established to minimize the total cost in the RIES scheduling cycle and construct a DRO scheduling model for RIES with HDR-EGS.By simulating a real small-scale RIES,the results show that HDR-EGS can effectively promote WP consumption and reduce the operating cost of the system.
文摘BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged.AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma(dCCA)who underwent pancreat-oduodenectomy(PD).METHODS This single-center study included 216 patients with dCCA after PD between January 1,2011,and December 31,2022.The individuals were categorized into two sets based on their systemic inflammatory response index(SIRI)levels:A low SIRI group(SIRI<1.5,n=123)and a high SIRI group(SIRI≥1.5,n=93).Inflam-matory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves.Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival(OS)and recurrence-free survival(RFS).RESULTS The study included a total of 216 patients,with 58.3%being male and a mean age of 65.6±9.6 years.123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA.SIRI had an area under the curve value of 0.674 for diagnosing dCCA,showing better performance than other inflammatory biomarkers.Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD,leading to lower OS[hazard ratios(HR)=1.868,P=0.006]and RFS(HR=0.949,P<0.001).Additionally,survival analysis indicated a significantly better prognosis for patients in the low SIRI group(P<0.001).CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.
基金Supported by National Natural Science Foundation of China,No.8236110677Natural Science Foundation of Gansu Province,No.18JR2RA033Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project,National Key Research and Development Program,No.2020RCXM076.
文摘BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.
文摘Digital integration within healthcare systems exacerbates their vulnerability to sophisticated ransomware threats, leading to severe operational disruptions and data breaches. Current defenses are typically categorized into active and passive measures that struggle to achieve comprehensive threat mitigation and often lack real-time response effectiveness. This paper presents an innovative ransomware defense system, ERAD, designed for healthcare environments that apply the MITRE ATT&CK Matrix to coordinate dynamic, stage-specific countermeasures throughout the ransomware attack lifecycle. By systematically identifying and addressing threats based on indicators of compromise (IOCs), the proposed system proactively disrupts the attack chain before serious damage occurs. Validation is provided through a detailed analysis of a system deployment against LockBit 3.0 ransomware, illustrating significant enhancements in mitigating the impact of the attack, reducing the cost of recovery, and strengthening the cybersecurity framework of healthcare organizations, but also applicable to other non-health sectors of the business world.
基金the financial support from the National Natural Science Foundation of China (No. 82372019, 82022034, 82173327)Jiangsu Province Natural Science Foundation of China (BK20200032)Double First Class Foundation of China Pharmaceutical University(CPUQNJC22_03)
文摘Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.
文摘BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.