Abstract:In recent years,sepsis has gradually become one of the medical and public health problems of concern to the society,with high morbidity and mortality and poor prognosis.Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by an imbalance in the host response to infection,and its main mechanism is an imbalance in the inflammatory response,which in turn leads to a series of reactions such as fatal tissue and organ damage and coagulation dysfunction.The main idea of treating the immune imbalance in sepsis is to suppress the early excessive inflammatory response and to improve the suppressive state of the organ immunity at the late stage.Xuebijing injection is suitable for systemic inflammatory response syndrome induced by infection;it can also be used in the treatment of multiple organ dysfunction syndrome in the period of impaired organ function,and it can be used to comprehensively regulate the immune imbalance of sepsis patients through the multi-targeting effect of different components,which effectively improves the prognosis of the patients.In this article,we review the progress of Xuebijin injection in the treatment of sepsis and provide new ideas for the immunotherapy of sepsis.

Abstract:Sepsis-associated encephalopathy(SAE)is a diffuse dysfunction of the nervous system resulting from sepsis originating outside the central nervous system.The elderly are a particularly vulnerable population,and clinical symptoms in elderly patients with SAE are often atypical,compounded by a high burden of underlying diseases and complications,which frequently leads to underdiagnosis or misdiagnosis.These patients are at increased risk of long-term or permanent central nervous system impairment,and rapid and accurate diagnosis and treatment for elderly SAE is critical.This expert consensus,grounded in evidence-based medicine and clinical experience,offers recommendations on the risk factors,clinical characteristics,diagnosis and treatment of geriatric SAE.The goal is to standardize the diagnosis and treatment process of SAE,improve diagnostic accuracy,reduce mortality,and enhance patients' outcomes.

Abstract:Objective To investigate the therapeutic potential of astragalus polysaccharides(APS)in modulating lipopolysaccharide(LPS)-induced aerobic glycolysis and ferroptosis in alveolar macrophages through the Nrf2/Keap1 signaling pathway.Methods An in vitro acute lung injury model was established by using LPS-stimulated alveolar macrophages.Cells were divided into five experimental groups:Control group,LPS group,Bardoxolone+LPS group,APS+LPS group,and ML385+APS+LPS group.Inflammatory cytokines[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)],oxidative stress markers[malonaldehyde(MDA),superoxide dismutase(SOD),reactive oxygen species(ROS)],glycolytic markers[lactate dehydrogenase(LDH),fructose 2,6-diphosphatase 3(PFKFB3),pyruvate kinase 2(PKM2),hexokinase 2(HK2)]and ferroptosis-related proteins[long chain acyl-CoA synthetase 4(ACSL4),cystine glutamate antiporter subunit(xCT),glutathione peroxidase 4(GPX4)and Nrf2/Keap1 signaling pathway components(nuclear/cytoplasmic Nrf2,Keap1)were analyzed by using enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(RT-qPCR)and Western blot.Results In comparison to the Control group,the LPS group exhibited elevated levels of IL-6,IL-1 β and TNF-α,alongside increased concentrations of MDA and ROS,and a reduction in SOD levels.Additionally,the mRNA and protein expression of LDH,PFKFB3,PKM2,HK2,ACSCL4 were upregulated,whereas the expression of xCT,GPX4 were downregulated.Nuclear expression of Nrf2 and Keap1 also decreased.Conversely,compared to the LPS group,there was a reduction in the expression levels of IL-6,IL-1β and TNF-α,decreased levels of MDA and ROS,as well as an increase in SOD levels in the APS+LPS group.Furthermore,the expression levels of LDH,PFKFB3,PKM2,HK2,ACSL4 were downregulated,while the expression levels of xCT and GPX4 were upregulated.The nuclear expression levels of Nrf2 and Keap1 were increased.Bardoxolone,a Nrf2 activator,partially mitigated the metabolic reprogramming and ferroptosis in LPS group,whereas the therapeutic efficacy in the APS+LPS group was diminished by the Nrf2 inhibitor ML385.Conclusions APS can modulate the Nrf2/Keap1 signaling pathway,suppress LPS-induced aerobic glycolysis and ferroptosis in alveolar macrophages,and mitigate alveolar macrophage injury.

Abstract:Objective To construct and validate risk prediction model of in-hospital mortality in the patients with acute myocardial infarction(AMI)complicated by cardiogenic shock(CS).Methods The 513 patients with AMI complicated by CS in the MIMIC-Ⅳ database were randomly divided into training set and validation set according to 6∶4 ratio,and 99 patients from the Cardiology Department in the First Affiliated Hospital of Chongqing Medical University from 2022 to 2023 was used for external validation set.The vital signs and laboratory test results within the first 24 h of admission were collected,retaining their maximum and minimum values.Variables for the model were selected by using best subset regression(BSR),and a predictive model and nomogram were subsequently developed.The predictive performance of the model was comprehensively assessed by the receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results The prediction model included four variables:age,minimum systolic blood pressure,maximum blood urea nitrogen,and maximum lactate.The area under ROC curve(AUC)was 0.813 in the training set and 0.800 in internal validation set,showing a good discriminative ability.In the external validation set,the AUC was 0.816,which was higher than that of the existing the intra-aortic balloon pump in cardiogenic shock Ⅱ(IABP-SHOCK Ⅱ)score and CardShock score,but the difference was not statistically significant.In addition,calibration curve indicated that the predictive values of the model were highly consistent with the actual results,DCA further confirmed the potential value of the model in clinical applications.Conclusions Our model,requiring only four easily accessible variables,provides a simple and effective tool for predicting in-hospital mortality in the patients with AMI complicated by CS.

Abstract:Objective To assess the efficacy and safety of intra-aortic balloon pump(IABP)combined with percutaneous coronary intervention(PCI)in the patients with acute myocardial infarction(AMI).Methods A systematic review was conducted on randomized controlled trials(RCTs)published in databases including PubMed,Embase,Wanfang and CNKI.Studies included AMI patients treated with IABP combined with or without PCI,and the data were analyzed by using RevMan 5.4 software.Results The results indicated that the combination therapy of IABP with PCI reduced the risk of mortality(RR=0.73,95％CI0.61-0.86,P=0.0002).Subgroup analysis showed greater benefits in the patients receiving timely IABP during PCI and those without concomitant cardiogenic shock(CS).Long-term follow-up data demonstrated IABP improved the prognosis(RR=0.84,95％CI 0.75-0.95,P=0.000 4).IABP in combination with PCI effectively reduced the risk of recurrent infarction,malignant arrhythmias,and heart failure exacerbations,but increased the risk of bleeding.Conclusions Combination therapy of IABP and PCI significantly reduces mortality risk and improves cardiac function in the patients with AMI,particularly benefiting AMI patients without concurrent CS.However,IABP treatment carries a risk of bleeding,necessitating careful consideration of risk-benefit profiles in clinical practice.

Abstract:Objective To evaluate the prognostic value of blood urea nitrogen to serum albumin ratio(B/A)in acute toxic mushroom poisoning.Methods This retrospective cohort study analyzed 241 patients admitted to the Emergency Intensive Care Unit(EICU)of the First Affiliated Hospital of Dalian Medical University from August 2011 to August 2023.Participants were divided into survival group(n=182)and death group(n=59)based on 28-day outcomes.Comparative analyses included B/A levels,organ dysfunction parameters,and receiver operating characteristic(ROC)curve was constructed.Results The death group exhibited significantly higher initial B/A(within 24 h),prothrombin time(PT),and alanine aminotransferase(ALT)(all P＜0.05),with lower platelet count(PLT)and albumin(ALB)levels compared to the survival group(all P＜0.05).Multivariate Cox regression identified high B/A and low ALB as independent mortality predictors for 28-day mortality in the patients with acute mushroom poisoning.The ROC curve results showed that both B/A and ALT had predictive ability for 28-day mortality in the patients with acute mushroom poisoning.The AUC of B/A combined with ALB was higher than that of B/A and ALB alone(0.728 vs.0.702,0.707,P＜0.05).Conclusions The combination of B/A and ALB has a high predictive value for 28-day mortality in the patients with acute mushroom poisoning.

Abstract:Objective To observe the effect of the Tiaochang formula(TCF)enema treatment on the level of inflammatory factors in the rats with sepsis-associated acute lung injury,and to explore the mechanism of action.Methods A total of 60 male SD rats were randomly allocated into the sham group,model group,low-dose TCF group,medium-dose TCF group,and high-dose TCF group,with 12 rats in each group.The sepsis-associated acute lung injury model was established by cecal ligation and puncture(CLP).The sham group and the model group were administered normal saline,while the low-dose,medium-dose,and high-dose TCF groups were given 2.2,4.4,and 8.8 g/d TCF liquid per day respectively.The status of the rats was observed three days after administration.Behavioral score,arterial blood gas,the levels of interleukin-6(IL-6)and interleukin-10(IL-10)in serum and lung tissue were measured.The intestine and left lung tissues after hematoxylin-eosin(HE)staining were used to observe the degree of tissue damage.The right lung tissue was dried,and the lung wet-to-dry weight ratio(W/D)was compared.Results Compared with the sham group,the behavioral scores of rats in the other groups increased,the level in the model group was notably higher than that in the other groups(P＜0.05).Compared with the sham operation group,the PaO2 level and PaO2/FiO2 index in the model group were significantly decreased,while the PaCO2 level was significantly increased(P＜0.05);Compared with the model group,the PaO2 level and PaO2/FiO2 index in the TCF group were significantly increased,and the PaCO2 level was significantly decreased(P＜0.05),with the high-dose group showing better improvement than the low-dose and medium-dose groups.Compared with the sham operation group,the W/D ratio of lung in the model group increased significantly(P＜0.05);Compared with the model group,the W/D ratio in the TCF group decreased significantly(P＜0.05),and the high-dose group showed a lower ratio than the low-dose and medium-dose groups.Compared with the sham group,the model group showed severe structural damage in the lungs and intestines,massive infiltration of inflammatory cells,and capillary dilation with hemorrhage.In the low-dose,medium-dose,and high-dose TCF groups,the tissue damage in the lungs and intestines of rats was alleviated,with reduced structural destruction.Compared with the sham group,the IL-10 levels were significantly lower in the remaining group,and IL-10 levels in the model group was lower than that in TCF group(P＜0.05);compared with the model group,the IL-6 levels in the TCF group was significantly lower(P＜0.05).Conclusions TCF can effectively reduce the degree of lung structural damage caused by sepsis in rats and alleviate the level of inflammatory response.

Abstract:Objective To assess respiratory muscle function by using ultrasound in healthy adults under varying inspiratory efforts and to establish a physiological model for predicting inspiratory effort.Methods A cross-sectional study was conducted in healthy subjects who met the inclusion criteria from June 2022 to December 2022.Inspiratory capacity during quiet breathing,moderate inspiration,and maximal inspiration were measured by using a portable pulmonary function meter to evaluate inspiratory effort.Simultaneously,bedside ultrasound was used to assess right diaphragm excursion,diaphragm thickness,and intercostal muscle thickness in these three states.The thickening fractions of the right diaphragm and intercostal muscle were calculated.Correlations of diaphragm excursion,diaphragm thickening fraction,intercostal muscle thickening fraction with inspiratory capacity were analyzed.Receiver operating characteristic curves were plotted to determine optimal cut-off values for diaphragm excursion,diaphragm thickening fraction and intercostal muscle thickening fraction based on area under the curve(AUC).Results A total of 65 subjects completed screening with an average age of(27.03±4.73)years;24 participants were male(37％).Diaphragm excursion during moderate and maximal inspiration was higher in males than in females(all P＜0.05).There were no statistically significant differences in diaphragm excursion during quiet breathing,diaphragm thicking fraction and intercostal muscle thickening fraction under different respiratory states between males and females(all P＞0.05).Diaphragm excursion as well as its associated thickening fractions showed significant correlations with inspiratory capacity(mL/kg ideal body weight),with correlation coefficients r being 0.83 for diaphragm excursion,0.75 for diaphragm thickening fraction,and 0.69 for intercostal muscle thickening fraction respectively(all P＜0.05).The linear regression equations were diaphragm excursion(cm)=1.26+0.09 × inspiratory capacity(mL/kg ideal body weight),diaphragm thickening fraction=-0.23+0.06 × inspiratory capacity(mL/kg ideal body weight)and intercostal muscle thickening fraction=-0.025+0.005 × inspiratory capacity(mL/kg ideal body weight).If≥moderate inspiratory effort was defined as relative inspiratory effort,the AUC of diaphragm excursion for predicting inspiratory effort was 0.96,the Youden index was 0.82,the best cut-off value was 2.33 cm,the sensitivity was 87.69％,and the specificity was 93.85％.The AUC of diaphragm thickening fraction for predicting inspiratory effort was 0.97,when the Youden index was 0.82,the best cut-off value was 0.45,the sensitivity was 89.23％,and the specificity was 92.31％.If the intercostal muscle thickening fraction＞0 was defined as absolute inspiratory effort,the AUC of inspiratory capacity for predicting inspiratory effort was 0.95,and when the Youden index was 0.80,the best cut-off value was 16 mL/kg ideal body weight,the sensitivity was 93.16％,the specificity was 87.18％,the corresponding diaphragm excursion was 2.70 cm,and the diaphragm thickening fraction was 0.73.Conclusions The use of ultrasound to assess the respiratory muscle motor function can determine the inspiratory effort in real time.

Abstract:Objective To develop and validate a nomogram model for early prediction of respiratory infectious disease severity in emergency triage,and to compare its clinical value with traditional scoring tools[modified early warning score(MEWS)and sequential organ failure assessment(SOFA)].Methods The data of a total of 7 615 patients were retrieved from December 2022 to March 2023,November 2023 to March 2024,and November 2024 to December 2024,and 4 727 eligible participants were included in the final analysis.In the training set of random sampling(70％),routinely available triage data were used as predictors(such as demographic data,vital signs,current disease,and past medical history).The severity was defined as the patient admitted to the intensive care unit after the emergency visit.Binary Logistic regression analysis was used to develop a nomogram to perform accurate calibration,identification and clinical application evaluation of the performance of the model.Results Predictors in the individualized prediction nomogram included age,pulse,respiratory rate,fever,shortness of breath,and the level of consciousness.The nomogram model showed good discrimination and good calibration,with the area under ROC curve(AUC)of the nomogram model was 0.830(95％CI 0.791～0.870)in the training set and 0.750(95％CI 0.638～0.864)in the validation set.Compared with MEWS and SOFA,the nomogram model demonstrated higher accuracy and specificity in predicting the severity of patients with respiratory infectious diseases.Conclusions The nomogram model of respiratory infectious diseases developed in this study for emergency triage has high accuracy in predicting the severity of respiratory infectious disease,which facilitates the rational allocation of healthcare resources and timely intervention for high-risk patients by emergency clinicians.

Abstract:Sepsis-associated encephalopathy(SAE)is one of the earliest and most common organ dysfunctions in the patients with sepsis,with an incidence of up to 70％.Recent studies have shown that the brain-gut axis plays a key role in the pathogenesis of SAE.This article systematically reviews the regulatory mechanisms of the brain-gut axis-mediated SAE occurrence and development,focuses on the role of the nervous system,endocrine system,immune system and intestinal microbiota in the pathogenesis of SAE,and discusses the therapeutic strategies targeting the brain-gut axis,so as to provide new ideas for the clinical prevention and treatment of SAE.

Abstract:Objective To explore the mechanism of carbon monoxide(CO)-induced neurodamage based on network toxicology.Methods This study analyzed the neurotoxic mechanism of CO by using network toxicology and molecular docking techniques.First,the three-dimensional structure of CO was obtained from PubChem,and its toxicity information was queried on the ProTox platform.The target gene set of CO was analyzed by using the Venn package,and brain injury-related genes were screened in combination with the GeneCards,OMIM,and TTD databases to construct the target gene set.Cytoscape was used to build an interaction network of CO targets and brain injury,identifying high-connectivity target proteins.Gene ontology(GO)and Kyoto encyclopedia of gene and genomes(KEGG)enrichment analyses were performed on key targets to identify the pathways related to CO poisoning and brain injury,with the results presented in a bubble chart.Finally,molecular docking analysis was conducted by using CB-dock2 to verify the binding ability of key target proteins to CO.Results This study constructed the CO-brain injury target network,revealing the mechanisms of CO damage to the nervous system,particularly the disruption of the blood-brain barrier.GO and KEGG enrichment analyses indicated that CO mediated neurodamage through the heme metabolism process and porphyrin synthesis pathway,with HMOX1 potentially playing a key role in this process.Conclusions HMOX1 possibly plays a critical role in further exploration of the neurotoxic mechanisms of CO.

Abstract:Fire accidents pose a significant threat to human health through toxic components released in pyrolytic smoke,with the respiratory system serving as the primary target organ.This exposure frequently induces smoke inhalation-induced acute lung injury(SI-ALI)with a pathophysiological condition characterized by complex mechanism.Recent years,domestic and foreign scholars have witnessed substantial advancements in global research efforts which focuses on establishing standardized animal models and elucidating the underlying pathological mechanisms of SI-ALI.This review provides a systematic synthesis of cutting-edge research advances in the field,with principal emphasis on elucidating standardized methodologies for SI-ALI model establishment and delineating its pathophysiological characteristics in order to provide a more effective theoretical basis and reference for the development of clinical prevention and treatment strategies in SI-ALI.