BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-...BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.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
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,as a non-limiting host infection disease,can be accompanied by serious complications such as organ failure,which seriously threatens patient quality of life.AIM To investigate the effect of early ste...BACKGROUND Sepsis,as a non-limiting host infection disease,can be accompanied by serious complications such as organ failure,which seriously threatens patient quality of life.AIM To investigate the effect of early stepwise cardiopulmonary rehabilitation on cardiopulmonary function and quality of life in patients evacuated from mechanical ventilation with sepsis.METHODS A total of 80 patients with sepsis who were hospitalized in our hospital from January 2021 to January 2022 were selected and divided into the observation group(n=40)and the control group(n=40)according to the random number table method.The observation group was treated with early stepwise cardiopulmonary rehabilitation,and the control group was treated with a conventional treatment regimen.Cardiac function indexes(central venous pressure,cardiac troponin I,B-type brain natriuretic peptide),lung function indicators(diaphragmatic mobility,changes in central venous oxygen saturation,oxygenation index),and quality of life(Quality of Life Evaluation Scale)were compared between the two groups after treatment.RESULTS After treatment,the central venous pressure,diaphragm mobility,central venous oxygen saturation,oxygenation index,and Quality of Life Evaluation Scale scores in the observation group were higher than those in the control group,and the differences were statistically significant(P<0.05).The observation group was less than that of the control group for other parameters,and the differences were statistically significant(P<0.05).CONCLUSION Early stepwise cardiopulmonary rehabilitation can effectively enhance cardiac and pulmonary function and improve the quality of life in patients evacuated from mechanical ventilation with sepsis.展开更多
BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical tec...BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.展开更多
BACKGROUND Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening.Patients usually experience depression and anxiety,which affect their sleep qualit...BACKGROUND Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening.Patients usually experience depression and anxiety,which affect their sleep quality and post-traumatic growth levels.AIM To investigate the effects of sepsis,a one-hour bundle(H1B)management was combined with psychological intervention in patients with sepsis.METHODS This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People’s Hospital between June 2022 and June 2023.According to different intervention methods,the participants were divided into a simple group(SG,n=150)and combined group(CG,n=150).H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG.The changes of negative emotion,sleep quality and post-traumatic growth and prognosis were compared between the two groups before(T0)and after(T1)intervention.RESULTS After intervention(T1),the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG(P<0.001).Sleep time,sleep quality,sleep efficiency,daytime dysfunction,sleep disturbance dimension score,and the total score in the CG were significantly lower than those in the SG(P<0.001).The appreciation of life,mental changes,relationship with others,personal strength dimension score,and total score of the CG were significantly higher than those of the SG(P<0.001).The scores for mental health,general health status,physiological function,emotional function,physical pain,social function,energy,and physiological function in the CG were significantly higher than those in the SG(P<0.001).The mechanical ventilation time,intensive care unit stay time,and 28-d mortality of the CG were significantly lower than those of the SG(P<0.05).CONCLUSION H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.展开更多
Background: Neonatal sepsis is known to result in 26% of mortalities in children below the age of five worldwide, countries in Sub-Saharan African recording the highest deaths. Although the deaths of neonates have red...Background: Neonatal sepsis is known to result in 26% of mortalities in children below the age of five worldwide, countries in Sub-Saharan African recording the highest deaths. Although the deaths of neonates have reduced world over up to 3.6 million counts, Chilenje General Hospital continues to register significant numbers of neonatal sepsis. This study aimed at investigating the factors associated with neonatal sepsis at Chilenje General Hospital in Lusaka, Zambia. Methods: An institution based cross-sectional study design was conducted at Chilenje General Hospital. Data were collected by the use of a researcher designed questionnaire and analysed using SPSS version 25. Frequencies were used for descriptive analysis while bivariate analysis was used to establish association among risk factors and outcome variables. Variables with significant association at 5% level were further subjected to multivariate analysis at α ≤ 0.05. Results: The study showed that out of 156 neonates, 40.4% (63/156) developed neonatal sepsis. Maternal factors that projected the incidence of sepsis amongst neonates were distance to nearest health facility [AOR: 6.3 (95% CI: 1.8 - 21.3), p = 0.003], occupation [AOR: 5.8 (95% CI: 1.2 - 27.6), p = 0.026], number of antenatal visits [AOR: 6.3 (95% CI: 1.9 - 21.6), p = 0.003], number of vaginal examinations [AOR: 10.8 (95% CI: 2.8 - 42), p = 0.001], and pregnancy induced hypertension [AOR: 5.4 (95% CI: 1.4 - 20), p = 0.013]. Neonatal risk factor which projected the incidence of sepsis was Neonate’s age [AOR: 18.8 (95% CI: 4.9 - 72.5), p = 0.000]. Conclusions: The chance of developing neonatal sepsis was strongly correlated with both mother and child variables, according to the study. In order to lower the chance of the neonate acquiring sepsis, encouraging maternal antenatal care use would assist to detect risk factors during prenatal, perinatal and postnatal care and apply the proper therapies.展开更多
Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: E...Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.展开更多
lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,t...lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.展开更多
Objective:To explore the value of using the venous-arterial carbon dioxide partial pressure difference and the arterial-venous oxygen content difference ratio(ΔP_(CO2)/Ca-v_(O2))as targets to guide early tissue hypop...Objective:To explore the value of using the venous-arterial carbon dioxide partial pressure difference and the arterial-venous oxygen content difference ratio(ΔP_(CO2)/Ca-v_(O2))as targets to guide early tissue hypoperfusion in sepsis in plateau areas.Methods:90 sepsis patients admitted to the Third People’s Hospital of Xining and Golmud People’s Hospital from June 2017 to December 2022 were selected as the research subjects,and they were divided into the Scv_(O2)(central venous oxygen saturation)group and theΔP_(CO2)/Ca-v_(O2)group,with 45 cases in each group.The two groups were treated with early shock resuscitation according to different protocols.The hemodynamic characteristics of the two groups of patients before and after resuscitation were observed,and the volume responsiveness was evaluated.The ROC(receiver operating characteristic)curve was used to analyze the significance ofΔP_(CO2)/Ca-v_(O2),Scv_(O2),lactate,lactate clearance,and urine output in evaluating patient prognosis and the correlation betweenΔP_(CO2)/Ca-v_(O2)and the above indicators was explored.Results:Compared with before resuscitation,after fluid resuscitation,the heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),cardiac index(CI),lactate,lactate clearance rate,and urine output of the two groups of patients were significantly improved(P<0.05);in terms of therapeutic effect,the 28-day mortality rate,6-hour fluid balance,and lactic acid clearance of theΔP_(CO2)/Ca-v_(O2)group were better than the Scv_(O2)group.The ROC characteristic curve showed that theΔP_(CO2)/Ca-v_(O2)value can effectively predict the prognosis of patients(AUC=0.907,sensitivity was 97%,specificity was 72.4%,and critical value was 1.84).ΔP_(CO2)/Ca-v_(O2)significantly correlated with Scv_(O2),lactic acid,and lactic acid clearance rate.Conclusion:TheΔP_(CO2)/Ca-v_(O2)value can be used to guide fluid resuscitation in early hypoperfusion in sepsis in plateau areas,improve patients’hemodynamics,reduce lactate indicators,and increase urine output.ΔP_(CO2)/Ca-v_(O2)level>1.84 can effectively improve patient prognosis.展开更多
Mortality, morbidity, early recognition, and treatment of sepsis remain a diagnostic dilemma for clinicians, in addition, the timely diagnosis of sepsis represents an ongoing clinical challenge. This review looks at t...Mortality, morbidity, early recognition, and treatment of sepsis remain a diagnostic dilemma for clinicians, in addition, the timely diagnosis of sepsis represents an ongoing clinical challenge. This review looks at the challenges of early recognition, the scope of the problem, the immunologic basis of the sepsis cascade, new frontiers related to interventions, and the role of antibiotics in an era of antimicrobial resistance. In Figure 1, once a patient is on the slippery slope of sepsis, the ability to reverse the momentum is challenging;hoping antibiotics, fluid resuscitation, vasopressors may buy time for the immunologic cascade to equilibrate to its homeostatic balance. While the development of septic shock is much more complex than pathogen proliferation, our understanding of the pathogenesis and ability to therapeutically intervene is in its infancy. Patients with sepsis frequently present for urgent medical care with undifferentiated infection and nonspecific symptoms. As 80% of patients with sepsis are initially treated in an Emergency Department, the burden of early recognition and intervention falls squarely on the shoulders of Emergency Department Clinicians. [1] This is an entity that occurs in all age groups, without regard to race, geography, or health status. Survival and mortality related to this clinical entity are poorly understood. Our understanding of sepsis needs to expand beyond the downstream effects and collateral damage of multiorgan dysfunction and failure. Immunologically, the antigenic triggers, be it invasive infection, severe injury, and systemic inflammation without concomitant infection, elicit similar pattern recognition receptors and innate host responses. If you are lucky enough to have survived an acute episode of sepsis, patients with sepsis often develop new adverse sequelae after treatment, a concept called persistent critical illness or post sepsis syndrome, characterized by long-term disability, and worsening chronic health conditions requiring re-hospitalization. [2]展开更多
BACKGROUND:Sepsis-associated encephalopathy(SAE) is a critical disease caused by sepsis.In addition to high mortality,SAE can also adversely aff ect life quality and lead to significant socioeconomic costs.This review...BACKGROUND:Sepsis-associated encephalopathy(SAE) is a critical disease caused by sepsis.In addition to high mortality,SAE can also adversely aff ect life quality and lead to significant socioeconomic costs.This review aims to explore the development of evaluation animal models of SAE,giving insight into the direction of future research in terms of its pathophysiology and therapy.METHODS:We performed a literature search from January 1,2000,to December 31,2022,in MEDLINE,PubMed,EMBASE,and Web of Science using related keywords.Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies.RESULTS:The animal models for sepsis are commonly induced through cecal ligation and puncture(CLP) or lipopolysaccharide(LPS) injection.SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase,or through Morris water maze(MWM),openfield test,fear condition(FC) test,inhibitory avoidance,and other tests during the late phase.CONCLUSION:CLP and LPS injection are the most common methods for establishing SAE animal models.Nervous reflexs cores,MWM,FC test,and inhibitory avoidance are widely used in SAE model analysis.Future research should focus on establishing a standardized system for SAE development and analysis.展开更多
BACKGROUND Urinary sepsis is frequently seen in patients with diabetes mellitus(DM)complicated with upper urinary tract calculi(UUTCs).Currently,the known risk factors of urinary sepsis are not uniform.AIM To analyze ...BACKGROUND Urinary sepsis is frequently seen in patients with diabetes mellitus(DM)complicated with upper urinary tract calculi(UUTCs).Currently,the known risk factors of urinary sepsis are not uniform.AIM To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression.METHODS We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People’s Hospital of Jincheng between February 2018 and May 2022.The patients were screened according to the inclusion and exclusion criteria,and 204 patients were enrolled.The patients were assigned to an occurrence group(n=78)and a nonoccurrence group(n=126).Logistic regression was adopted to analyze the risk factors for urinary sepsis,and a risk prediction model was established.RESULTS Gender,age,history of lumbago and abdominal pain,operation time,urine leukocytes(U-LEU)and urine glucose(U-GLU)were independent risk factors for patients with concurrent urinary sepsis(P<0.05).Risk score=0.794×gender+0.941×age+0.901×history of lumbago and abdominal pain-1.071×operation time+1.972×U-LEU+1.541×U-GLU.The occurrence group had notably higher risk scores than the nonoccurrence group(P<0.0001).The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801,with specificity of 73.07%,sensitivity of 79.36%and Youden index of 52.44%.CONCLUSION Sex,age,history of lumbar and abdominal pain,operation time,ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.展开更多
Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection.It is a complex syndrome and is characterized by physiologic,pathologic and biochemical abnormalities in ...Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection.It is a complex syndrome and is characterized by physiologic,pathologic and biochemical abnormalities in response to an infection.Diagnosis of sepsis is based on history,physical examination and other investigations(including biomarkers)which may help to increase the certainty of diagnosis.Biomarkers have been evaluated in the past for many diseases and have been evaluated for sepsis as well.Biomarkers may find a possible role in diagnosis,prognostication,therapeutic monitoring and anti-microbial stewardship in sepsis.Since the pathophysiology of sepsis is quite complex and is incompletely understood,a single biomarker that may be robust enough to provide all information has not been found as of yet.However,many biomarkers have been studied and some of them have applications at the bedside and guide clinical decision-making.We evaluated the PubMed database to search for sepsis biomarkers for diagnosis,prognosis and possible role in antibiotic escalation and de-escalation.Clinical trials,meta-analyses,systematic reviews and randomized controlled trials were included.Commonly studied biomarkers such as procalcitonin,Soluble urokinase-type plasminogen activator(Supar),presepsin,soluble triggering receptor expressed on myeloid cells 1,interleukin 6,C-reactive protein,etc.,have been described for their possible applications as biomarkers in septic patients.The sepsis biomarkers are still an area of active research with newer evidence adding to the knowledge base continuously.For patients presenting with sepsis,early diagnosis and prompt resuscitation and early administration of anti-microbials(preferably within 1 h)and source control are desired goals.Biomarkers may help us in the diagnosis,prognosis and therapeutic monitoring of septic patients.The marker redefining our view on sepsis is yet a mirage that clinicians and researchers continue to chase.展开更多
BACKGROUND:Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure.Endothelial cells(ECs)exhibit specific metabolic traits and release metabolites to adapt to the septic state in the ...BACKGROUND:Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure.Endothelial cells(ECs)exhibit specific metabolic traits and release metabolites to adapt to the septic state in the blood to maintain vascular homeostasis.METHODS:Web of Science and PubMed were searched from inception to October 1,2022.The search was limited to the English language only.Two reviewers independently identified studies related to EC metabolism in sepsis.The exclusion criteria were duplicate articles according to multiple search criteria.RESULTS:Sixty articles were included,and most of them were cell and animal studies.These studies reported the role of glycolysis,oxidative phosphorylation,fatty acid metabolism,and amino acid metabolism in EC homeostasis.including glycolysis,oxidative phosphorylation,fatty acid metabolism and amino acid metabolism.However,dysregulation of EC metabolism can contribute to sepsis progression.CONCLUSION:There are few clinical studies on EC metabolism in sepsis.Related research mainly focuses on basic research,but some scientific problems have also been clarified.Therefore,this review may provide an overall comprehension and novel aspects of EC metabolism in sepsis.展开更多
Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of deat...Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.展开更多
Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on th...Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.展开更多
Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods T...Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods The effect of RSV on V.vulnificus cytolysin(VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays.Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction,western blot,and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V.vulnificus-induced sepsis mouse model.Results RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells.RSV also inhibited the inflammatory response,had a protective effect on histopathological changes,and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages,lung,spleen,and liver tissues of V.vulnificus-induced septic mice in vivo.Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V.vulnificusinduced septic mice.RSV also improved the survival of V.vulnificus-induced septic mice.Conclusion Our findings collectively demonstrate that RSV prevented V.vulnificus-induced sepsis by attenuating necroptosis,highlighting its potency in the clinical management of V.vulnificus-induced sepsis.展开更多
Objective To investigate the effects of the pre-shock state on the mortality of patients with sepsis.Methods We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university h...Objective To investigate the effects of the pre-shock state on the mortality of patients with sepsis.Methods We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state,and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.Results A total of 303 patients(groups: sepsis 135 [44.6%]), pre-shock state(93 [30.7%]), and septic shock(75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group,but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.Conclusion The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.展开更多
基金supported by Beijing Natural Science Foundation(No.7222162 to Dr.Hui Liu)。
文摘BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.
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 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.
文摘BACKGROUND Sepsis,as a non-limiting host infection disease,can be accompanied by serious complications such as organ failure,which seriously threatens patient quality of life.AIM To investigate the effect of early stepwise cardiopulmonary rehabilitation on cardiopulmonary function and quality of life in patients evacuated from mechanical ventilation with sepsis.METHODS A total of 80 patients with sepsis who were hospitalized in our hospital from January 2021 to January 2022 were selected and divided into the observation group(n=40)and the control group(n=40)according to the random number table method.The observation group was treated with early stepwise cardiopulmonary rehabilitation,and the control group was treated with a conventional treatment regimen.Cardiac function indexes(central venous pressure,cardiac troponin I,B-type brain natriuretic peptide),lung function indicators(diaphragmatic mobility,changes in central venous oxygen saturation,oxygenation index),and quality of life(Quality of Life Evaluation Scale)were compared between the two groups after treatment.RESULTS After treatment,the central venous pressure,diaphragm mobility,central venous oxygen saturation,oxygenation index,and Quality of Life Evaluation Scale scores in the observation group were higher than those in the control group,and the differences were statistically significant(P<0.05).The observation group was less than that of the control group for other parameters,and the differences were statistically significant(P<0.05).CONCLUSION Early stepwise cardiopulmonary rehabilitation can effectively enhance cardiac and pulmonary function and improve the quality of life in patients evacuated from mechanical ventilation with sepsis.
文摘BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.
基金Supported by Key R&D and Promotion Special Project(Science and Technology Research)in Henan Province in 2023,No.232102310089.
文摘BACKGROUND Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening.Patients usually experience depression and anxiety,which affect their sleep quality and post-traumatic growth levels.AIM To investigate the effects of sepsis,a one-hour bundle(H1B)management was combined with psychological intervention in patients with sepsis.METHODS This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People’s Hospital between June 2022 and June 2023.According to different intervention methods,the participants were divided into a simple group(SG,n=150)and combined group(CG,n=150).H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG.The changes of negative emotion,sleep quality and post-traumatic growth and prognosis were compared between the two groups before(T0)and after(T1)intervention.RESULTS After intervention(T1),the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG(P<0.001).Sleep time,sleep quality,sleep efficiency,daytime dysfunction,sleep disturbance dimension score,and the total score in the CG were significantly lower than those in the SG(P<0.001).The appreciation of life,mental changes,relationship with others,personal strength dimension score,and total score of the CG were significantly higher than those of the SG(P<0.001).The scores for mental health,general health status,physiological function,emotional function,physical pain,social function,energy,and physiological function in the CG were significantly higher than those in the SG(P<0.001).The mechanical ventilation time,intensive care unit stay time,and 28-d mortality of the CG were significantly lower than those of the SG(P<0.05).CONCLUSION H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.
文摘Background: Neonatal sepsis is known to result in 26% of mortalities in children below the age of five worldwide, countries in Sub-Saharan African recording the highest deaths. Although the deaths of neonates have reduced world over up to 3.6 million counts, Chilenje General Hospital continues to register significant numbers of neonatal sepsis. This study aimed at investigating the factors associated with neonatal sepsis at Chilenje General Hospital in Lusaka, Zambia. Methods: An institution based cross-sectional study design was conducted at Chilenje General Hospital. Data were collected by the use of a researcher designed questionnaire and analysed using SPSS version 25. Frequencies were used for descriptive analysis while bivariate analysis was used to establish association among risk factors and outcome variables. Variables with significant association at 5% level were further subjected to multivariate analysis at α ≤ 0.05. Results: The study showed that out of 156 neonates, 40.4% (63/156) developed neonatal sepsis. Maternal factors that projected the incidence of sepsis amongst neonates were distance to nearest health facility [AOR: 6.3 (95% CI: 1.8 - 21.3), p = 0.003], occupation [AOR: 5.8 (95% CI: 1.2 - 27.6), p = 0.026], number of antenatal visits [AOR: 6.3 (95% CI: 1.9 - 21.6), p = 0.003], number of vaginal examinations [AOR: 10.8 (95% CI: 2.8 - 42), p = 0.001], and pregnancy induced hypertension [AOR: 5.4 (95% CI: 1.4 - 20), p = 0.013]. Neonatal risk factor which projected the incidence of sepsis was Neonate’s age [AOR: 18.8 (95% CI: 4.9 - 72.5), p = 0.000]. Conclusions: The chance of developing neonatal sepsis was strongly correlated with both mother and child variables, according to the study. In order to lower the chance of the neonate acquiring sepsis, encouraging maternal antenatal care use would assist to detect risk factors during prenatal, perinatal and postnatal care and apply the proper therapies.
文摘Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.
基金The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.
基金2017 Xining Citizens’Biotechnology Plan Project(Project number:2017-K-15)。
文摘Objective:To explore the value of using the venous-arterial carbon dioxide partial pressure difference and the arterial-venous oxygen content difference ratio(ΔP_(CO2)/Ca-v_(O2))as targets to guide early tissue hypoperfusion in sepsis in plateau areas.Methods:90 sepsis patients admitted to the Third People’s Hospital of Xining and Golmud People’s Hospital from June 2017 to December 2022 were selected as the research subjects,and they were divided into the Scv_(O2)(central venous oxygen saturation)group and theΔP_(CO2)/Ca-v_(O2)group,with 45 cases in each group.The two groups were treated with early shock resuscitation according to different protocols.The hemodynamic characteristics of the two groups of patients before and after resuscitation were observed,and the volume responsiveness was evaluated.The ROC(receiver operating characteristic)curve was used to analyze the significance ofΔP_(CO2)/Ca-v_(O2),Scv_(O2),lactate,lactate clearance,and urine output in evaluating patient prognosis and the correlation betweenΔP_(CO2)/Ca-v_(O2)and the above indicators was explored.Results:Compared with before resuscitation,after fluid resuscitation,the heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),cardiac index(CI),lactate,lactate clearance rate,and urine output of the two groups of patients were significantly improved(P<0.05);in terms of therapeutic effect,the 28-day mortality rate,6-hour fluid balance,and lactic acid clearance of theΔP_(CO2)/Ca-v_(O2)group were better than the Scv_(O2)group.The ROC characteristic curve showed that theΔP_(CO2)/Ca-v_(O2)value can effectively predict the prognosis of patients(AUC=0.907,sensitivity was 97%,specificity was 72.4%,and critical value was 1.84).ΔP_(CO2)/Ca-v_(O2)significantly correlated with Scv_(O2),lactic acid,and lactic acid clearance rate.Conclusion:TheΔP_(CO2)/Ca-v_(O2)value can be used to guide fluid resuscitation in early hypoperfusion in sepsis in plateau areas,improve patients’hemodynamics,reduce lactate indicators,and increase urine output.ΔP_(CO2)/Ca-v_(O2)level>1.84 can effectively improve patient prognosis.
文摘Mortality, morbidity, early recognition, and treatment of sepsis remain a diagnostic dilemma for clinicians, in addition, the timely diagnosis of sepsis represents an ongoing clinical challenge. This review looks at the challenges of early recognition, the scope of the problem, the immunologic basis of the sepsis cascade, new frontiers related to interventions, and the role of antibiotics in an era of antimicrobial resistance. In Figure 1, once a patient is on the slippery slope of sepsis, the ability to reverse the momentum is challenging;hoping antibiotics, fluid resuscitation, vasopressors may buy time for the immunologic cascade to equilibrate to its homeostatic balance. While the development of septic shock is much more complex than pathogen proliferation, our understanding of the pathogenesis and ability to therapeutically intervene is in its infancy. Patients with sepsis frequently present for urgent medical care with undifferentiated infection and nonspecific symptoms. As 80% of patients with sepsis are initially treated in an Emergency Department, the burden of early recognition and intervention falls squarely on the shoulders of Emergency Department Clinicians. [1] This is an entity that occurs in all age groups, without regard to race, geography, or health status. Survival and mortality related to this clinical entity are poorly understood. Our understanding of sepsis needs to expand beyond the downstream effects and collateral damage of multiorgan dysfunction and failure. Immunologically, the antigenic triggers, be it invasive infection, severe injury, and systemic inflammation without concomitant infection, elicit similar pattern recognition receptors and innate host responses. If you are lucky enough to have survived an acute episode of sepsis, patients with sepsis often develop new adverse sequelae after treatment, a concept called persistent critical illness or post sepsis syndrome, characterized by long-term disability, and worsening chronic health conditions requiring re-hospitalization. [2]
基金supported by the National High Level Hospital Clinical Research Fund (2022-PUMCH-B-109)CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-1-I2M-020)。
文摘BACKGROUND:Sepsis-associated encephalopathy(SAE) is a critical disease caused by sepsis.In addition to high mortality,SAE can also adversely aff ect life quality and lead to significant socioeconomic costs.This review aims to explore the development of evaluation animal models of SAE,giving insight into the direction of future research in terms of its pathophysiology and therapy.METHODS:We performed a literature search from January 1,2000,to December 31,2022,in MEDLINE,PubMed,EMBASE,and Web of Science using related keywords.Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies.RESULTS:The animal models for sepsis are commonly induced through cecal ligation and puncture(CLP) or lipopolysaccharide(LPS) injection.SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase,or through Morris water maze(MWM),openfield test,fear condition(FC) test,inhibitory avoidance,and other tests during the late phase.CONCLUSION:CLP and LPS injection are the most common methods for establishing SAE animal models.Nervous reflexs cores,MWM,FC test,and inhibitory avoidance are widely used in SAE model analysis.Future research should focus on establishing a standardized system for SAE development and analysis.
文摘BACKGROUND Urinary sepsis is frequently seen in patients with diabetes mellitus(DM)complicated with upper urinary tract calculi(UUTCs).Currently,the known risk factors of urinary sepsis are not uniform.AIM To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression.METHODS We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People’s Hospital of Jincheng between February 2018 and May 2022.The patients were screened according to the inclusion and exclusion criteria,and 204 patients were enrolled.The patients were assigned to an occurrence group(n=78)and a nonoccurrence group(n=126).Logistic regression was adopted to analyze the risk factors for urinary sepsis,and a risk prediction model was established.RESULTS Gender,age,history of lumbago and abdominal pain,operation time,urine leukocytes(U-LEU)and urine glucose(U-GLU)were independent risk factors for patients with concurrent urinary sepsis(P<0.05).Risk score=0.794×gender+0.941×age+0.901×history of lumbago and abdominal pain-1.071×operation time+1.972×U-LEU+1.541×U-GLU.The occurrence group had notably higher risk scores than the nonoccurrence group(P<0.0001).The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801,with specificity of 73.07%,sensitivity of 79.36%and Youden index of 52.44%.CONCLUSION Sex,age,history of lumbar and abdominal pain,operation time,ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.
文摘Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection.It is a complex syndrome and is characterized by physiologic,pathologic and biochemical abnormalities in response to an infection.Diagnosis of sepsis is based on history,physical examination and other investigations(including biomarkers)which may help to increase the certainty of diagnosis.Biomarkers have been evaluated in the past for many diseases and have been evaluated for sepsis as well.Biomarkers may find a possible role in diagnosis,prognostication,therapeutic monitoring and anti-microbial stewardship in sepsis.Since the pathophysiology of sepsis is quite complex and is incompletely understood,a single biomarker that may be robust enough to provide all information has not been found as of yet.However,many biomarkers have been studied and some of them have applications at the bedside and guide clinical decision-making.We evaluated the PubMed database to search for sepsis biomarkers for diagnosis,prognosis and possible role in antibiotic escalation and de-escalation.Clinical trials,meta-analyses,systematic reviews and randomized controlled trials were included.Commonly studied biomarkers such as procalcitonin,Soluble urokinase-type plasminogen activator(Supar),presepsin,soluble triggering receptor expressed on myeloid cells 1,interleukin 6,C-reactive protein,etc.,have been described for their possible applications as biomarkers in septic patients.The sepsis biomarkers are still an area of active research with newer evidence adding to the knowledge base continuously.For patients presenting with sepsis,early diagnosis and prompt resuscitation and early administration of anti-microbials(preferably within 1 h)and source control are desired goals.Biomarkers may help us in the diagnosis,prognosis and therapeutic monitoring of septic patients.The marker redefining our view on sepsis is yet a mirage that clinicians and researchers continue to chase.
基金supported by the National Natural Science Foundation of China(82272236)Key Emergency Medical Disciplines and Specialities Program of Guangzhou(2021-2023)。
文摘BACKGROUND:Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure.Endothelial cells(ECs)exhibit specific metabolic traits and release metabolites to adapt to the septic state in the blood to maintain vascular homeostasis.METHODS:Web of Science and PubMed were searched from inception to October 1,2022.The search was limited to the English language only.Two reviewers independently identified studies related to EC metabolism in sepsis.The exclusion criteria were duplicate articles according to multiple search criteria.RESULTS:Sixty articles were included,and most of them were cell and animal studies.These studies reported the role of glycolysis,oxidative phosphorylation,fatty acid metabolism,and amino acid metabolism in EC homeostasis.including glycolysis,oxidative phosphorylation,fatty acid metabolism and amino acid metabolism.However,dysregulation of EC metabolism can contribute to sepsis progression.CONCLUSION:There are few clinical studies on EC metabolism in sepsis.Related research mainly focuses on basic research,but some scientific problems have also been clarified.Therefore,this review may provide an overall comprehension and novel aspects of EC metabolism in sepsis.
基金supported by the National Natural Science Foundation of China(82222038,82020108021 and 82260372)the Chongqing Special Project for Academicians(cstc2020yszx-jcyjX0004)the Chongqing Outstanding Youth Foundation and Science Foundation for Outstanding Youth of the Army Medical Centre(2019CXJSB004)。
文摘Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
基金support by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research,China(Grant No.:2020YFE0205100)the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)+9 种基金the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002)the National Natural Science Foundation of China(Grant Nos.:82141001,82274182,82074098,82173914)the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund,China(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen,China(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen,China(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the National Key R&D Program of China Key Projects for International Cooperation on Science,Technology and Innovation(Grant No.:2020YFE0205100)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10),Shenzhen Governmental Sustainable Development Fund,China(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases,China(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties,China(Grant No.:SZGSP001).
文摘Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
基金supported by the Beijing Municipal Natural Science Foundation[7204314]the Medical Innovation Project Foundation[CX19027]the Young Researcher Supporting Program[QNF19066]of the Chinese PLA General Hospital.
文摘Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods The effect of RSV on V.vulnificus cytolysin(VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays.Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction,western blot,and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V.vulnificus-induced sepsis mouse model.Results RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells.RSV also inhibited the inflammatory response,had a protective effect on histopathological changes,and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages,lung,spleen,and liver tissues of V.vulnificus-induced septic mice in vivo.Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V.vulnificusinduced septic mice.RSV also improved the survival of V.vulnificus-induced septic mice.Conclusion Our findings collectively demonstrate that RSV prevented V.vulnificus-induced sepsis by attenuating necroptosis,highlighting its potency in the clinical management of V.vulnificus-induced sepsis.
基金funded by the Clinical Cohort Construction Program of Peking University Third Hospital [No.BYSYDL2021019]the National Natural Science Foundation of China [Grant No. 82272197]。
文摘Objective To investigate the effects of the pre-shock state on the mortality of patients with sepsis.Methods We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state,and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.Results A total of 303 patients(groups: sepsis 135 [44.6%]), pre-shock state(93 [30.7%]), and septic shock(75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group,but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.Conclusion The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.
