Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories...Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories:Typical and atypical.A typical DFA is secondary to a severe infection in the foot,often initiated by minor breaches in skin integrity that allow pathogens to enter and proliferate.This form often progresses rapidly due to the underlying diabetic pathophysiology of neuropathy,microvascular disease,and hyperglycemia,which facilitate infection spread and tissue necrosis.This form of DFA can present as one of a number of severe infective pathologies including pyomyositis,necrotizing fasciitis,and myonecrosis,all of which can lead to systemic sepsis and multiorgan failure.An atypical DFA,however,is not primarily infection-driven.It can occur secondary to either ischemia or Charcot arthropathy.Management of the typical DFA involves prompt diagnosis,aggressive infection control,and a multidisciplinary approach.Treatment can be guided by the current International Working Group on the Diabetic Foot/Infectious Diseases Society of America guidelines on diabetic foot infections,and the combined British Orthopaedic Foot and Ankle Society-Vascular Society guidelines.This article highlights the importance of early recognition,comprehensive management strategies,and the need for further research to establish standardized protocols and improve clinical outcomes for patients with DFA.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohor...BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.展开更多
Background:Sepsis is a life-threatening disease with high mortality and a poor prognosis,partly due to a lack of effective treatments.Therefore,more effective treatments are urgently needed.Methods:Eight databases wer...Background:Sepsis is a life-threatening disease with high mortality and a poor prognosis,partly due to a lack of effective treatments.Therefore,more effective treatments are urgently needed.Methods:Eight databases were searched for use of traditional Chinese medicine(TCM) for sepsis.A meta-analysis was performed using Stata 15.0 software.The 28-day mortality,length of hospital stay,and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE-Ⅱ) score were the outcomes of this study.The Cochrane Collaboration tool for assessing risk of bias was used for quality assessment.Results:Ten studies with a total of 847 patients were included in this meta-analysis.Compared with the control group,the experimental group had lower 28-day mortality(relative risk [RR] 0.67;95% confidence interval [CI] 0.53 to 0.84;P=0.001),shorter hospital stay(weighted mean difference [WMD]-2.17;95% CI:-3.2 to -1.14;P=0.000) and lower APACHE-Ⅱ score(WMD-2.164;95% CI:-3.236 to -1.091;P=0.000).Conclusion:Our results demonstrate that TCM together with standard Western medicine was associated with significantly lower 28-day mortality,APACHE Ⅱ scores,and shorter hospital intensive care unit stays,suggesting that TCM might be an effective alternative treatment for sepsis.展开更多
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1,2]Septic shock,the most severe form of sepsis,is characterized by circulatory and cellular/metabolic abnor...Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1,2]Septic shock,the most severe form of sepsis,is characterized by circulatory and cellular/metabolic abnormalities,and can increase mortality to>40%.[1-3]Early recognition and risk stratification of septic shock are crucial but challenging because of the heterogeneity of its presentation and progression.展开更多
BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecula...BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.展开更多
BACKGROUND Sepsis-associated liver injury(SLI)is a severe and prevalent complication of sepsis.AIM To explore the literature on SLI via a bibliometric approach.METHODS Reviews and articles correlated with SLI publishe...BACKGROUND Sepsis-associated liver injury(SLI)is a severe and prevalent complication of sepsis.AIM To explore the literature on SLI via a bibliometric approach.METHODS Reviews and articles correlated with SLI published from January 1,2000 to October 28,2023 were searched from the Web of Science Core Collection.Then,the searched data were analyzed using VOSviewer,CiteSpace,and R language.RESULTS There were 787 publications involved in this paper,comprising 745 articles and 42 reviews.China,the United States,and Germany are the primary publication sources in this area.Studies related to SLI primarily focused on mechanisms of pathogenesis,as evidenced by analyzing keywords,references,and the counting of original research.These studies mainly involved tumor necrosis factor alpha,inflammation,oxidative stress,and nuclear factor-kappa B.CONCLUSION There is significant growth in the research on SLI.Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms.According to the analyzed literature,the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.展开更多
Electromagnetic interference shielding(EMI SE)modules are the core com-ponent of modern electronics.However,the tra-ditional metal-based SE modules always take up indispensable three-dimensional space inside electroni...Electromagnetic interference shielding(EMI SE)modules are the core com-ponent of modern electronics.However,the tra-ditional metal-based SE modules always take up indispensable three-dimensional space inside electronics,posing a major obstacle to the integra-tion of electronics.The innovation of integrating 3D-printed conformal shielding(c-SE)modules with packaging materials onto core electronics offers infinite possibilities to satisfy ideal SE func-tion without occupying additional space.Herein,the 3D printable carbon-based inks with various proportions of graphene and carbon nanotube nanoparticles are well-formulated by manipulating their rheological peculiarity.Accordingly,the free-constructed architectures with arbitrarily-customized structure and multifunctionality are created via 3D printing.In particular,the SE performance of 3D-printed frame is up to 61.4 dB,simultaneously accompanied with an ultralight architecture of 0.076 g cm^(-3) and a superhigh specific shielding of 802.4 dB cm3 g^(-1).Moreover,as a proof-of-concept,the 3D-printed c-SE module is in situ integrated into core electronics,successfully replacing the traditional metal-based module to afford multiple functions for electromagnetic compatibility and thermal dissipa-tion.Thus,this scientific innovation completely makes up the blank for assembling carbon-based c-SE modules and sheds a brilliant light on developing the next generation of high-performance shielding materials with arbitrarily-customized structure for integrated electronics.展开更多
As the manufacturing process of silicon-based integrated circuits(ICs)approaches its physical limit,the quantum effect of silicon-based field-effect transistors(FETs)has become increasingly evident.And the burgeoning ...As the manufacturing process of silicon-based integrated circuits(ICs)approaches its physical limit,the quantum effect of silicon-based field-effect transistors(FETs)has become increasingly evident.And the burgeoning carbon-based semiconductor technology has become one of the most disruptive technologies in the post-Moore era.As one-dimensional nanomaterials,carbon nanotubes(CNTs)are far superior to silicon at the same technology nodes of FETs because of their excellent electrical transport and scaling properties,rendering them the most competitive material in the next-generation ICs technology.However,certain challenges impede the industrialization of CNTs,particularly in terms of material preparation,which significantly hinders the development of CNT-based ICs.Focusing on CNT-based ICs technology,this review summarizes its main technical status,development trends,existing challenges,and future development directions.展开更多
BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(I...BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.展开更多
In the realm of the synthesis of heat-integrated distillation configurations,the conventional approach for exploring more heat integration possibilities typically entails the splitting of a single column into a twocol...In the realm of the synthesis of heat-integrated distillation configurations,the conventional approach for exploring more heat integration possibilities typically entails the splitting of a single column into a twocolumn configuration.However,this approach frequently necessitates tedious enumeration procedures,resulting in a considerable computational burden.To surmount this formidable challenge,the present study introduces an innovative remedy:The proposition of a superstructure that encompasses both single-column and multiple two-column configurations.Additionally,a simultaneous optimization algorithm is applied to optimize both the process parameters and heat integration structures of the twocolumn configurations.The effectiveness of this approach is demonstrated through a case study focusing on industrial organosilicon separation.The results underscore that the superstructure methodology not only substantially mitigates computational time compared to exhaustive enumeration but also furnishes solutions that exhibit comparable performance.展开更多
High-chromium vanadium-titanium magnetite(HVTM)is a crucial polymetallic-associated resource to be developed.The allpellet operation is a blast furnace trend that aims to reduce carbon dioxide emissions in the future....High-chromium vanadium-titanium magnetite(HVTM)is a crucial polymetallic-associated resource to be developed.The allpellet operation is a blast furnace trend that aims to reduce carbon dioxide emissions in the future.By referencing the production data of vanadium-titanium magnetite blast furnaces,this study explored the softening-melting behavior of high-chromium vanadium-titanium magnetite and obtained the optimal integrated burden based on flux pellets.The results show that the burden with a composition of 70wt%flux pellets and 30wt%acid pellets exhibits the best softening-melting properties.In comparison to that of the single burden,the softening-melting characteristic temperature of this burden composition was higher.The melting interval first increased from 307 to 362℃and then decreased to 282℃.The maximum pressure drop(ΔPmax)decreased from 26.76 to 19.01 kPa.The permeability index(S)dropped from 4643.5 to 2446.8 kPa·℃.The softening-melting properties of the integrated burden were apparently improved.The acid pellets played a role in withstanding load during the softening process.The flux pellets in the integrated burden exhibited a higher slag melting point,which increased the melting temperature during the melting process.The slag homogeneity and the TiC produced by over-reduction led to the gas permeability deterioration of the single burden.The segregation of the flux and acid pellets in the HVTM proportion and basicity mainly led to the better softening-melting properties of the integrated burden.展开更多
Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this ...Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this paper,we propose pixelated programmable Si_(3)N_(4)PICs with record-high 20-level intermediate states at 785 nm wavelength.Such flexibility in phase or amplitude modulation is achieved by a programmable Sb_(2)S_(3)matrix,the footprint of whose elements can be as small as 1.2μm,limited only by the optical diffraction limit of anin-house developed pulsed laser writing system.We believe our work lays the foundation for laser-writing ultra-high-level(20 levels and even more)programmable photonic systems and metasurfaces based on phase change materials,which could catalyze diverse applications such as programmable neuromorphic photonics,biosensing,optical computing,photonic quantum computing,and reconfigurable metasurfaces.展开更多
BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endotheli...BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endothelial dysfunction.These pathological changes lead to systemic organ injury.However,an analysis using bibliometric methods has not yet been conducted in the field of EDS.This study was conducted to provide an overview of knowledge structure and research trends in the fi eld of EDS.METHODS:Based on previous research,a literature search was performed in the Web of Science Core Collection(WoSCC)for publications associated with EDS published between the year 2003 and 2023.Various types of data from the publications,such as citation frequency,authorship,keywords and highly cited articles,were extracted.The"Create Citation Report"feature in the WoSCC was employed to calculate the Hirsch index(h-index)and average citations per item(ACI)of authors,institutions,and countries.To conduct bibliometric and visualization analyses,three bibliometric tools were used,including R-bibliometrix,CiteSpace(co-citation analysis of references),and VOSviewer(co-authorship analysis of institutions,co-authorship analysis of authors,co-occurrence analysis of keywords).RESULTS:After excluding invalid records,the study finaly included 4,536 publications with 135,386 citations.Most of these publications originated in the USA,China,Germany,Canada,and Japan.Harvard University emerged as the most prolifi c institution,while professor Jong-Sup Bae and his research team at Kyungpook National University emerged as authors with the greatest infl uence.The"protein C","tissue factor","thrombin","glycocalyx",“acute kidney injury”,“syndecan-1”and“biomarker”were identifi ed as prominent areas of research.Future research may focus on molecular mechanisms(such as as vascular endothelial[VE]-cadherin regulation)and therapeutic interventions to enhance endothelial repair and function.CONCLUSION:Our findings show a growing interest in EDS research.Key areas for future research include signaling pathways,molecular mechanisms,endothelial repair,and interactions between endothelial cells and other cell types in sepsis.展开更多
BACKGROUND Arthroscopic rotator cuff repair is a common surgical treatment for rotator cuff injuries(RCIs).Although this procedure has certain clinical advantages,it requires rehabilitation management interventions to...BACKGROUND Arthroscopic rotator cuff repair is a common surgical treatment for rotator cuff injuries(RCIs).Although this procedure has certain clinical advantages,it requires rehabilitation management interventions to ensure therapeutic efficacy.AIM To investigate the effect of integrated traditional Chinese medicine and Western medicine(TCM-WM)under the multidisciplinary team(MDT)model on the postoperative recovery of patients undergoing arthroscopic surgery for RCIs.METHODS This study enrolled 100 patients who underwent arthroscopic rotator cuff repair for RCIs at the Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine between June 2021 and May 2024.They were divided into a control group(n=48)that received routine rehabilitation treatment and an experimental group(n=52)that received TCM-WM under the MDT model(e.g.,acupuncture,TCM traumatology and orthopedics,and rehabilitation).The results of the Constant–Murley Shoulder Score(CMS),Visual Analogue Scale(VAS),Shoulder Pain and Disability Index(SPADI),muscular strength evaluation,and shoulder range of motion(ROM)assessments were analyzed.RESULTS After treatment,the experimental group showed significantly higher CMS scores in terms of pain,functional activity,shoulder joint mobility,and muscular strength than the baseline and those of the control group.The experimental group also exhibited significantly lower VAS and SPADI scores than the baseline and those of the control group.In addition,the experimental group showed significantly enhanced muscular strength(forward flexor and external and internal rotator muscles)and shoulder ROM(forward flexion,abduction,and lateral abduction)after treatment compared with the control group.CONCLUSION TCM-WM under the MDT model improved shoulder joint function,relieved postoperative pain,promoted postoperative functional recovery,and facilitated the recovery of muscular strength and shoulder ROM in patients with RCIs who underwent arthroscopic rotator cuff repair.展开更多
Strongyloidiasis stercoralis can cause disease when larvae invade the human body through the skin or mucosa and can also infect a host when the host ingests its eggs.[1]Strongyloidiasis lacks characteristic manifestat...Strongyloidiasis stercoralis can cause disease when larvae invade the human body through the skin or mucosa and can also infect a host when the host ingests its eggs.[1]Strongyloidiasis lacks characteristic manifestations,and its clinical symptoms are related to the immune response of the host and the degree of infection.Immunodefi cient patients with underlying disease or who are receiving long-term corticosteroid treatment are more prone to developing severe disease.[2]The present study reports a case of Strongyloides stercoralis-induced sepsis and acute respiratory distress syndrome(ARDS)in a patient with Guillain-Barrésyndrome.展开更多
Sepsis is a lethal condition characterized by multiple organ dysfunction due to disrupted host responses to severe infections.[1]Aff ected patients often have a Sequential Organ Failure Assessment(SOFA)score≥2.[2]Pat...Sepsis is a lethal condition characterized by multiple organ dysfunction due to disrupted host responses to severe infections.[1]Aff ected patients often have a Sequential Organ Failure Assessment(SOFA)score≥2.[2]Patients with a SOFA score<2 and at least one of the following were considered as“suspected sepsis”:(1)quick SOFA(qSOFA)score≥2;(2)SOFA score=1;or(3)National Early Warning Score(NEWS)4-6.[3]Compared with studies on fluid resuscitation in sepsis patients,there are few studies on fluid management in patients with suspected sepsis.Therefore,we conducted a retrospective cohort study to evaluate the relationship between fluid management and disease progression in suspected sepsis patients.展开更多
The coronavirus disease 2019(COVID-19)pandemic,triggered by the novel coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has ravaged the globe,resulting in a staggering loss of life and wreaking h...The coronavirus disease 2019(COVID-19)pandemic,triggered by the novel coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has ravaged the globe,resulting in a staggering loss of life and wreaking havoc on the worldwide economy.[1,2]Sepsis is a cascade of abnormal responses provoked by infection,leading to a critical deterioration in organ function that poses a life-threatening risk.[3]However,it is unclear from published reports whether COVID-19 and sepsis are commonly aff ected by molecular factors.Therefore,we performed a bioinformatics analysis to uncover shared diagnostic genes and potential mechanisms between COVID-19 and sepsis.展开更多
Sepsis is a life-threatening organ dysfunction caused by the host’s dysregulated response to infection.[1]With an estimated 48.9 million cases globally each year,sepsis accounts for 19.7%of the total global deaths.[2...Sepsis is a life-threatening organ dysfunction caused by the host’s dysregulated response to infection.[1]With an estimated 48.9 million cases globally each year,sepsis accounts for 19.7%of the total global deaths.[2]Early identification of sepsis patients with poor prognosis is crucial for personalized treatment and precision intervention.展开更多
文摘Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories:Typical and atypical.A typical DFA is secondary to a severe infection in the foot,often initiated by minor breaches in skin integrity that allow pathogens to enter and proliferate.This form often progresses rapidly due to the underlying diabetic pathophysiology of neuropathy,microvascular disease,and hyperglycemia,which facilitate infection spread and tissue necrosis.This form of DFA can present as one of a number of severe infective pathologies including pyomyositis,necrotizing fasciitis,and myonecrosis,all of which can lead to systemic sepsis and multiorgan failure.An atypical DFA,however,is not primarily infection-driven.It can occur secondary to either ischemia or Charcot arthropathy.Management of the typical DFA involves prompt diagnosis,aggressive infection control,and a multidisciplinary approach.Treatment can be guided by the current International Working Group on the Diabetic Foot/Infectious Diseases Society of America guidelines on diabetic foot infections,and the combined British Orthopaedic Foot and Ankle Society-Vascular Society guidelines.This article highlights the importance of early recognition,comprehensive management strategies,and the need for further research to establish standardized protocols and improve clinical outcomes for patients with DFA.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
基金Supported by National Natural Science Foundation of China,No.82174461Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0201-22Technology Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A01811.
文摘BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.
基金The National Key Research and Development Program(2018YFC1705900)。
文摘Background:Sepsis is a life-threatening disease with high mortality and a poor prognosis,partly due to a lack of effective treatments.Therefore,more effective treatments are urgently needed.Methods:Eight databases were searched for use of traditional Chinese medicine(TCM) for sepsis.A meta-analysis was performed using Stata 15.0 software.The 28-day mortality,length of hospital stay,and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE-Ⅱ) score were the outcomes of this study.The Cochrane Collaboration tool for assessing risk of bias was used for quality assessment.Results:Ten studies with a total of 847 patients were included in this meta-analysis.Compared with the control group,the experimental group had lower 28-day mortality(relative risk [RR] 0.67;95% confidence interval [CI] 0.53 to 0.84;P=0.001),shorter hospital stay(weighted mean difference [WMD]-2.17;95% CI:-3.2 to -1.14;P=0.000) and lower APACHE-Ⅱ score(WMD-2.164;95% CI:-3.236 to -1.091;P=0.000).Conclusion:Our results demonstrate that TCM together with standard Western medicine was associated with significantly lower 28-day mortality,APACHE Ⅱ scores,and shorter hospital intensive care unit stays,suggesting that TCM might be an effective alternative treatment for sepsis.
基金supported by the National Natural Science Foundation of China(no.82374069)the Beijing Municipal Administration of Hospitals’Youth Program(no.QML20170105)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support“Yangfan”Project(no.ZYLX201802)。
文摘Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1,2]Septic shock,the most severe form of sepsis,is characterized by circulatory and cellular/metabolic abnormalities,and can increase mortality to>40%.[1-3]Early recognition and risk stratification of septic shock are crucial but challenging because of the heterogeneity of its presentation and progression.
基金supported by Hunan Province Key Research and Development Program(2020SKC2004).
文摘BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.
基金Supported by National Key R&D Program Projects,No.2022YFC2009804。
文摘BACKGROUND Sepsis-associated liver injury(SLI)is a severe and prevalent complication of sepsis.AIM To explore the literature on SLI via a bibliometric approach.METHODS Reviews and articles correlated with SLI published from January 1,2000 to October 28,2023 were searched from the Web of Science Core Collection.Then,the searched data were analyzed using VOSviewer,CiteSpace,and R language.RESULTS There were 787 publications involved in this paper,comprising 745 articles and 42 reviews.China,the United States,and Germany are the primary publication sources in this area.Studies related to SLI primarily focused on mechanisms of pathogenesis,as evidenced by analyzing keywords,references,and the counting of original research.These studies mainly involved tumor necrosis factor alpha,inflammation,oxidative stress,and nuclear factor-kappa B.CONCLUSION There is significant growth in the research on SLI.Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms.According to the analyzed literature,the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.
基金This work is financially supported by the National Natural Science Foundation of China(52303036)the Natural Science Foundation of Guangxi Province(2020GXNSFAA297028)+4 种基金the Guangxi Science and Technology Base and Talent Special Project(GUIKE AD23026179)the International Science&Technology Cooperation Project of Chengdu(2021-GH03-00009-HZ)the Program of Innovative Research Team for Young Scientists of Sichuan Province(22CXTD0019)the Natural Science Foundation of Sichuan Province(2023NSFSC0986)the Opening Project of State Key Laboratory of Polymer Materials Engineering(Sichuan University)(Sklpme2023-3-18).
文摘Electromagnetic interference shielding(EMI SE)modules are the core com-ponent of modern electronics.However,the tra-ditional metal-based SE modules always take up indispensable three-dimensional space inside electronics,posing a major obstacle to the integra-tion of electronics.The innovation of integrating 3D-printed conformal shielding(c-SE)modules with packaging materials onto core electronics offers infinite possibilities to satisfy ideal SE func-tion without occupying additional space.Herein,the 3D printable carbon-based inks with various proportions of graphene and carbon nanotube nanoparticles are well-formulated by manipulating their rheological peculiarity.Accordingly,the free-constructed architectures with arbitrarily-customized structure and multifunctionality are created via 3D printing.In particular,the SE performance of 3D-printed frame is up to 61.4 dB,simultaneously accompanied with an ultralight architecture of 0.076 g cm^(-3) and a superhigh specific shielding of 802.4 dB cm3 g^(-1).Moreover,as a proof-of-concept,the 3D-printed c-SE module is in situ integrated into core electronics,successfully replacing the traditional metal-based module to afford multiple functions for electromagnetic compatibility and thermal dissipa-tion.Thus,this scientific innovation completely makes up the blank for assembling carbon-based c-SE modules and sheds a brilliant light on developing the next generation of high-performance shielding materials with arbitrarily-customized structure for integrated electronics.
基金supported by National Natural Science Foundation of China(Grant No.52022078)Shaanxi Provincial Key Research and Development Program(Grant No.2021ZDLGY10-02,2019ZDLGY01-09)。
文摘As the manufacturing process of silicon-based integrated circuits(ICs)approaches its physical limit,the quantum effect of silicon-based field-effect transistors(FETs)has become increasingly evident.And the burgeoning carbon-based semiconductor technology has become one of the most disruptive technologies in the post-Moore era.As one-dimensional nanomaterials,carbon nanotubes(CNTs)are far superior to silicon at the same technology nodes of FETs because of their excellent electrical transport and scaling properties,rendering them the most competitive material in the next-generation ICs technology.However,certain challenges impede the industrialization of CNTs,particularly in terms of material preparation,which significantly hinders the development of CNT-based ICs.Focusing on CNT-based ICs technology,this review summarizes its main technical status,development trends,existing challenges,and future development directions.
文摘BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.
文摘In the realm of the synthesis of heat-integrated distillation configurations,the conventional approach for exploring more heat integration possibilities typically entails the splitting of a single column into a twocolumn configuration.However,this approach frequently necessitates tedious enumeration procedures,resulting in a considerable computational burden.To surmount this formidable challenge,the present study introduces an innovative remedy:The proposition of a superstructure that encompasses both single-column and multiple two-column configurations.Additionally,a simultaneous optimization algorithm is applied to optimize both the process parameters and heat integration structures of the twocolumn configurations.The effectiveness of this approach is demonstrated through a case study focusing on industrial organosilicon separation.The results underscore that the superstructure methodology not only substantially mitigates computational time compared to exhaustive enumeration but also furnishes solutions that exhibit comparable performance.
基金supported by the National Natural Science Foundation of China (Nos.52174277 and 52204309)the China Postdoctoral Science Foundation (No.2022M720683).
文摘High-chromium vanadium-titanium magnetite(HVTM)is a crucial polymetallic-associated resource to be developed.The allpellet operation is a blast furnace trend that aims to reduce carbon dioxide emissions in the future.By referencing the production data of vanadium-titanium magnetite blast furnaces,this study explored the softening-melting behavior of high-chromium vanadium-titanium magnetite and obtained the optimal integrated burden based on flux pellets.The results show that the burden with a composition of 70wt%flux pellets and 30wt%acid pellets exhibits the best softening-melting properties.In comparison to that of the single burden,the softening-melting characteristic temperature of this burden composition was higher.The melting interval first increased from 307 to 362℃and then decreased to 282℃.The maximum pressure drop(ΔPmax)decreased from 26.76 to 19.01 kPa.The permeability index(S)dropped from 4643.5 to 2446.8 kPa·℃.The softening-melting properties of the integrated burden were apparently improved.The acid pellets played a role in withstanding load during the softening process.The flux pellets in the integrated burden exhibited a higher slag melting point,which increased the melting temperature during the melting process.The slag homogeneity and the TiC produced by over-reduction led to the gas permeability deterioration of the single burden.The segregation of the flux and acid pellets in the HVTM proportion and basicity mainly led to the better softening-melting properties of the integrated burden.
基金funded by the National Nature Science Foundation of China(Grant Nos.52175509 and 52130504)National Key Research and Development Program of China(2017YFF0204705)2021 Postdoctoral Innovation Research Plan of Hubei Province(0106100226)。
文摘Multi-level programmable photonic integrated circuits(PICs)and optical metasurfaces have gained widespread attention in many fields,such as neuromorphic photonics,opticalcommunications,and quantum information.In this paper,we propose pixelated programmable Si_(3)N_(4)PICs with record-high 20-level intermediate states at 785 nm wavelength.Such flexibility in phase or amplitude modulation is achieved by a programmable Sb_(2)S_(3)matrix,the footprint of whose elements can be as small as 1.2μm,limited only by the optical diffraction limit of anin-house developed pulsed laser writing system.We believe our work lays the foundation for laser-writing ultra-high-level(20 levels and even more)programmable photonic systems and metasurfaces based on phase change materials,which could catalyze diverse applications such as programmable neuromorphic photonics,biosensing,optical computing,photonic quantum computing,and reconfigurable metasurfaces.
基金supported by the National Natural Science Foundation of China(82272236)the Plan on Enhancing scientific research in GMU(YCZ)and the Key Emergency Medical Disciplines and Specialties Program of Guangzhou(0F05001)(2021-2023).
文摘BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endothelial dysfunction.These pathological changes lead to systemic organ injury.However,an analysis using bibliometric methods has not yet been conducted in the field of EDS.This study was conducted to provide an overview of knowledge structure and research trends in the fi eld of EDS.METHODS:Based on previous research,a literature search was performed in the Web of Science Core Collection(WoSCC)for publications associated with EDS published between the year 2003 and 2023.Various types of data from the publications,such as citation frequency,authorship,keywords and highly cited articles,were extracted.The"Create Citation Report"feature in the WoSCC was employed to calculate the Hirsch index(h-index)and average citations per item(ACI)of authors,institutions,and countries.To conduct bibliometric and visualization analyses,three bibliometric tools were used,including R-bibliometrix,CiteSpace(co-citation analysis of references),and VOSviewer(co-authorship analysis of institutions,co-authorship analysis of authors,co-occurrence analysis of keywords).RESULTS:After excluding invalid records,the study finaly included 4,536 publications with 135,386 citations.Most of these publications originated in the USA,China,Germany,Canada,and Japan.Harvard University emerged as the most prolifi c institution,while professor Jong-Sup Bae and his research team at Kyungpook National University emerged as authors with the greatest infl uence.The"protein C","tissue factor","thrombin","glycocalyx",“acute kidney injury”,“syndecan-1”and“biomarker”were identifi ed as prominent areas of research.Future research may focus on molecular mechanisms(such as as vascular endothelial[VE]-cadherin regulation)and therapeutic interventions to enhance endothelial repair and function.CONCLUSION:Our findings show a growing interest in EDS research.Key areas for future research include signaling pathways,molecular mechanisms,endothelial repair,and interactions between endothelial cells and other cell types in sepsis.
基金General Project of Health and Family Planning Scientific Research of Pudong New Area Health Commission:Evaluation of the Clinical Effectiveness of the Integrated Traditional Chinese and Western Medicine Clinical Program for Accelerating Postoperative Recovery of Patients with Rotator cuff Injury under the Multidisciplinary Team Mode,No.PW2021A-66Shanghai Municipal Health Commission Key Department of Integrated Traditional Chinese and Western MedicinePeak Discipline of Traditional Chinese Medicine(Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine),Shanghai Pudong New Area Health Commission,No.YC-2023-0601.
文摘BACKGROUND Arthroscopic rotator cuff repair is a common surgical treatment for rotator cuff injuries(RCIs).Although this procedure has certain clinical advantages,it requires rehabilitation management interventions to ensure therapeutic efficacy.AIM To investigate the effect of integrated traditional Chinese medicine and Western medicine(TCM-WM)under the multidisciplinary team(MDT)model on the postoperative recovery of patients undergoing arthroscopic surgery for RCIs.METHODS This study enrolled 100 patients who underwent arthroscopic rotator cuff repair for RCIs at the Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine between June 2021 and May 2024.They were divided into a control group(n=48)that received routine rehabilitation treatment and an experimental group(n=52)that received TCM-WM under the MDT model(e.g.,acupuncture,TCM traumatology and orthopedics,and rehabilitation).The results of the Constant–Murley Shoulder Score(CMS),Visual Analogue Scale(VAS),Shoulder Pain and Disability Index(SPADI),muscular strength evaluation,and shoulder range of motion(ROM)assessments were analyzed.RESULTS After treatment,the experimental group showed significantly higher CMS scores in terms of pain,functional activity,shoulder joint mobility,and muscular strength than the baseline and those of the control group.The experimental group also exhibited significantly lower VAS and SPADI scores than the baseline and those of the control group.In addition,the experimental group showed significantly enhanced muscular strength(forward flexor and external and internal rotator muscles)and shoulder ROM(forward flexion,abduction,and lateral abduction)after treatment compared with the control group.CONCLUSION TCM-WM under the MDT model improved shoulder joint function,relieved postoperative pain,promoted postoperative functional recovery,and facilitated the recovery of muscular strength and shoulder ROM in patients with RCIs who underwent arthroscopic rotator cuff repair.
基金supported by the Medical Scientific Research Foundation of Guangdong Province(A2022506)Natural Science Foundation of Guangdong Province(2023A1515010267)Cerebrovascular Disease Youth Innovation(Z-2016-20-2201).
文摘Strongyloidiasis stercoralis can cause disease when larvae invade the human body through the skin or mucosa and can also infect a host when the host ingests its eggs.[1]Strongyloidiasis lacks characteristic manifestations,and its clinical symptoms are related to the immune response of the host and the degree of infection.Immunodefi cient patients with underlying disease or who are receiving long-term corticosteroid treatment are more prone to developing severe disease.[2]The present study reports a case of Strongyloides stercoralis-induced sepsis and acute respiratory distress syndrome(ARDS)in a patient with Guillain-Barrésyndrome.
文摘Sepsis is a lethal condition characterized by multiple organ dysfunction due to disrupted host responses to severe infections.[1]Aff ected patients often have a Sequential Organ Failure Assessment(SOFA)score≥2.[2]Patients with a SOFA score<2 and at least one of the following were considered as“suspected sepsis”:(1)quick SOFA(qSOFA)score≥2;(2)SOFA score=1;or(3)National Early Warning Score(NEWS)4-6.[3]Compared with studies on fluid resuscitation in sepsis patients,there are few studies on fluid management in patients with suspected sepsis.Therefore,we conducted a retrospective cohort study to evaluate the relationship between fluid management and disease progression in suspected sepsis patients.
基金supported by the Zhejiang Provincial Basic Public Welfare Research Program of Zhejiang Province(LGF21H150002)Ningbo Municipal Natural Science Foundation(2023J134)+1 种基金Zhejiang Medicine and Health Science and Technology Project(2020KY249&2019KY572)Zhejiang Medicine and Health Science and Technology Project(2022RC245&2023KY255).
文摘The coronavirus disease 2019(COVID-19)pandemic,triggered by the novel coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has ravaged the globe,resulting in a staggering loss of life and wreaking havoc on the worldwide economy.[1,2]Sepsis is a cascade of abnormal responses provoked by infection,leading to a critical deterioration in organ function that poses a life-threatening risk.[3]However,it is unclear from published reports whether COVID-19 and sepsis are commonly aff ected by molecular factors.Therefore,we performed a bioinformatics analysis to uncover shared diagnostic genes and potential mechanisms between COVID-19 and sepsis.
基金funded by the Natural Science Foundation of Guangdong Province(KC0120220208)Guangzhou Municipal Health Commission(2023P-TS25)National Natural Science Foundation Cultivation Project of Guangdong Provincial People’s Hospital(KY0120220030).
文摘Sepsis is a life-threatening organ dysfunction caused by the host’s dysregulated response to infection.[1]With an estimated 48.9 million cases globally each year,sepsis accounts for 19.7%of the total global deaths.[2]Early identification of sepsis patients with poor prognosis is crucial for personalized treatment and precision intervention.