Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is sig...Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.展开更多
Acute eosinophilic pneumonia(AEP) is a pulmonary condition characterized by acute febrile illness and respiratory distress,with bilateral pulmonary infiltrates,particularly eosinophilic infiltration of the lungs.^([1]...Acute eosinophilic pneumonia(AEP) is a pulmonary condition characterized by acute febrile illness and respiratory distress,with bilateral pulmonary infiltrates,particularly eosinophilic infiltration of the lungs.^([1])Amiodarone,a widely applied antiarrhythmic agent,has been reported as a potential cause of drug-induced AEP.^([2]) Most reported cases of amiodarone-induced AEP typically occur following prolonged exposure for two months or more.展开更多
Aortic saddle embolism(ASE)is a rare but catastrophic vascular emergency characterized by acute occlusion of the aortic bifurcation,leading to bilateral lower limb ischemia and multiorgan dysfunction.Despite advances ...Aortic saddle embolism(ASE)is a rare but catastrophic vascular emergency characterized by acute occlusion of the aortic bifurcation,leading to bilateral lower limb ischemia and multiorgan dysfunction.Despite advances in imaging and surgical techniques,ASE has high morbidity and mortality rates,particularly when diagnosis or intervention is delayed.Here,we report two patients admitted to our center to increase awareness among emergency physicians.展开更多
Hypertriglyceridemia(HTG)is a common and significant contributor to acute pancreatitis(AP).Caffeine has been reported to have a protective effect against pancreatic disorders.However,the role of caffeine in hypertrigl...Hypertriglyceridemia(HTG)is a common and significant contributor to acute pancreatitis(AP).Caffeine has been reported to have a protective effect against pancreatic disorders.However,the role of caffeine in hypertriglyceridemia acute pancreatitis(HAP)is still unknown.To investigate a new understanding of the relationship between caffeine and gut microbiota in HAP development.Using multi-omics analysis of 71 HAP and HTG patients,their characteristics of intestinal microecology were detected.HTG mice models were established through either pharmacological induction(P-407 intraperitoneal injection)or genetic ablation of GPIHBP1(GPIHBP1^(−/−)).Genes deferentially expressed in the gut were identified by RNA sequencing and the role of caffeine in reshaping gut microbial networks was investigated.Caffeine levels decreased significantly in HAP patients and were inversely correlated with the severity of HAP.Caffeine maintained the intestinal homeostasis and attenuated HAP through a gut microbiota-dependent manner in the mouse model.Specially,the commensal Faecalibacterium prausnitzii,which contributed most in distinguishing the differences between HTG and HAP patients,has been found to be related to the effect of caffeine on alleviating HAP.RNA sequencing combined with TLR4^(−/−)mice revealed that TLR4/NLRP3 may be the key signaling pathway for caffeine to maintain intestinal homeostasis and alleviating HAP.This study reveals the gut metabolites and microbiota characteristics of HAP and HTG patients,and explores the therapeutic potential of caffeine against HAP from the perspective of gut microbiota.展开更多
Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)h...Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.展开更多
BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suita...BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suitable for rapid clinical application.METHODS:In this multi-center retrospective cohort study,AAS patient data from three hospitals were analyzed.The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region,with Peking University Third Hospital data serving as the external test set.Four machine learning algorithms—logistic regression(LR),multilayer perceptron(MLP),Gaussian naive Bayes(GNB),and random forest(RF)—were used to develop predictive models based on 34 early-accessible clinical variables.A simplifi ed model was then derived based on fi ve key variables(Stanford type,pericardial eff usion,asymmetric peripheral arterial pulsation,decreased bowel sounds,and dyspnea)via Least Absolute Shrinkage and Selection Operator(LASSO)regression to improve ED applicability.RESULTS:A total of 929 patients were included in the modeling cohort,and 210 were included in the external test set.Four machine learning models based on 34 clinical variables were developed,achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85,respectively.The simplifi ed model incorporating fi ve key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78,respectively.Both models showed robust calibration and predictive stability across datasets.CONCLUSION:Both kinds of models were built based on machine learning tools,and proved to have certain prediction performance and extrapolation.展开更多
Currently, glucocorticoids are the only treatment option for acute gout attacks in patients with chronic kidney disease (CKD) and progressive renal dysfunction. Management becomes particularly challenging when steroid...Currently, glucocorticoids are the only treatment option for acute gout attacks in patients with chronic kidney disease (CKD) and progressive renal dysfunction. Management becomes particularly challenging when steroid therapy is contraindicated, poorly tolerated, or ineffective. IL-1β monoclonal antibodies offer potent, targeted anti-inflammatory effects and have been approved for the treatment of gout, providing new therapeutic hope for this population. Here, we report a case of a patient with CKD and progressively worsening renal function who experienced an acute gout attack requiring dialysis. Treatment with the IL-1β monoclonal antibody Firsekibart produced rapid and remarkable anti-inflammatory and analgesic effects, effectively controlling the gout attack, improving renal function, and allowing discontinuation of dialysis.展开更多
This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to ...This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to age-related immune dysfunction,whereas EEN has been demonstrated to improve clinical prognosis,reduce infection and complication rates,and shor ten hospital stays.However,ongoing debates exist regarding the optimal timing,route selection,and complication management of EEN.Through a systematic review of the literature,this study synthesizes current evidence on EEN in elderly SAP populations,critically examines unresolved clinical controversies,and proposes future research priorities to inform evidence-based practice.展开更多
BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making ...BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making it a signifi cant public health concern.This study is to determine the prevalence and factors associated with acute pain among emergency trauma patients.METHODS:A multicenter cross-sectional study was conducted.Data were collected via interviewer-administered questionnaires and patient chart review.The data were analyzed via the statistical package for social science version 25.Bivariable and multivariable logistic regression analyses were used.Variables with a P-value<0.05 were considered statistically signifi cant.RESULTS:A total of 397 patients were included in the study,for a response rate of 96.8%.The prevalence of pain during admission was 91.9%(95%confi dence intervals[95%CIs]:88.8%-94.4%).Blunt trauma(adjusted odds ratio[aOR]=2.82;95%CI:1.23-6.45),analgesia before admission to the emergency department(aOR=2.71;95%CI:1.16-6.36),documentation of pain severity in the chart(aOR=2.71;95%CI:1.16-6.36),analgesia provided within two hours after admission(aOR=7.60;95%CI:2.79-20.68),use of non-pharmacological pain management methods(aOR=3.09;95%CI:1.35-7.08)and availability of analgesia(aOR=3.95;95%CI:1.36-11.43)were associated with acute pain experience.CONCLUSION:The prevalence of acute pain among emergency trauma patients was high in the study area.Analgesia should be administered prior to admission,and non-pharmacological pain management should be implemented.Moreover,training on pain assessment and management should be provided for healthcare providers in the emergency department.展开更多
Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually wit...Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.展开更多
Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of arti...Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.展开更多
Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ ...The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC_(50) values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments.展开更多
Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusio...Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.展开更多
Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury...Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.展开更多
Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy....Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.Methods:Sprague-Dawley rats were randomly divided into four groups:control,cisplatin,cisplatin+GP-17,and GP-17 alone.Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury,while GP-17 was given orally at 40 mg/kg/day for 7 d.The levels of serum creatinine and blood urea nitrogen,superoxide dismutase activity,and malondialdehyde content were measured.Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury.Moreover,the expression of mitophagy-related proteins,including PINK1,Parkin,LC3,and p62,and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays.Furthermore,human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17,with or without PINK1 siRNA transfection.Cell viability,apoptosis,reactive oxygen species levels,mitochondrial membrane potential,and the protein expression associated with the PINK1/Parkin pathway were measured.Results:In rats with cisplatin-induced acute kidney injury,GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen,attenuated tubular damage and mitochondrial ultrastructural injury,and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content.GP-17 further upregulated the protein levels of PINK1,Parkin,and LC3-Ⅱ/Ⅰratio while promoting p62 degradation,indicating enhanced mitophagic flux.In HK-2 cells,GP-17(20μM)co-treatment markedly attenuated cisplatin-induced cytotoxicity,apoptosis,reactive oxygen species overproduction,and mitochondrial depolarization.However,all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.Conclusions:GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy,which facilitates the clearance of damaged mitochondria,alleviates oxidative stress,and inhibits renal cell apoptosis.These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.展开更多
Objective:To investigate the effect of“72-hour proactive follow-up”led by respiratory specialist nurses on reducing the 30-day readmission rate in patients with acute exacerbation of chronic obstructive pulmonary di...Objective:To investigate the effect of“72-hour proactive follow-up”led by respiratory specialist nurses on reducing the 30-day readmission rate in patients with acute exacerbation of chronic obstructive pulmonary disease(COPD)after hospital discharge.Methods:A randomized controlled trial was conducted involving 60 patients with acute exacerbation of COPD admitted from September 2024 to September 2025.The participants were divided into a control group and an observation group,with 30 individuals in each group.The control group received routine discharge guidance nursing measures,including instructions on medication use,key points for condition monitoring,and scheduling of follow-up appointments.The observation group implemented“72-hour proactive follow-up”nursing measures,which included telephone follow-up within 72 hours after discharge,quantitative assessment of respiratory symptoms,dynamic adjustment of medication regimens,and personalized health education.The 30-day readmission rate,mMRC dyspnea index,CAT quality of life score,and other parameters were compared between the two groups.Results:The 30-day readmission rate in the observation group was significantly lower than that in the control group(p<0.05).The mMRC dyspnea index(1.8±0.5)in the observation group was significantly lower than that in the control group(2.5±0.7)(p<0.05).The CAT quality of life score(18.2±3.1)in the observation group was significantly higher than that in the control group(22.4±4.2)(p<0.05).The patient satisfaction score(92.5±4.3)in the observation group was higher than that in the control group(85.6±5.8)(p<0.05).Conclusion:The“72-hour proactive follow-up”nursing intervention demonstrates a favorable effect in reducing readmission rates,exhibiting significant clinical practical value.It can optimize the allocation of medical resources,effectively enhance patients’self-management efficacy,and holds prominent value for clinical promotion and application.展开更多
AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longit...AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longitudinal observational study,detailed medical histories of APAC patients and comprehensive ophthalmic examinations at final followup were collected.Logistic regression analysis was performed to identify predictors of blindness.Univariate and multivariate linear regression analyses were conducted to determine risk factors associated with visual outcomes.RESULTS:This study included 39 affected eyes of 31 subjects(26 females)with an average age of 74.1±8.0y.At 6.7±4.2y after APAC attack,2(5.7%)eyes had bestcorrected visual acuity(VA)worse than 3/60.Advanced glaucomatous visual field loss was observed in 15(39.5%)affected eyes and 5(25.0%)fellow eyes.Nine affected eyes(23.7%)had GON,and 11(28.9%)were blind.Six(15.4%)affected eyes and 2(9.1%)fellow eyes had suspicious progression.A significantly higher blindness rate in factory workers compared to office workers.Logistic regression identified that worse VA at attack(OR 10.568,95%CI 1.288-86.695;P=0.028)and worse early postoperative VA(OR 13.214,95%CI 1.157-150.881;P=0.038)were risk factors for blindness.Multivariate regression showed that longer duration of elevated intraocular pressure(P=0.004)and worse early postoperative VA(P=0.009)were associated with worse visual outcomes.CONCLUSION:Despite LE surgery,some APAC patients experience continued visual function deterioration.Lifelong monitoring is necessary.Target pressure and progression rates should be re-evaluated during follow-up.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
文摘Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.
基金supported by the Anhui Provincial Health and Medical Research Project (AHWJ2023A30277)。
文摘Acute eosinophilic pneumonia(AEP) is a pulmonary condition characterized by acute febrile illness and respiratory distress,with bilateral pulmonary infiltrates,particularly eosinophilic infiltration of the lungs.^([1])Amiodarone,a widely applied antiarrhythmic agent,has been reported as a potential cause of drug-induced AEP.^([2]) Most reported cases of amiodarone-induced AEP typically occur following prolonged exposure for two months or more.
文摘Aortic saddle embolism(ASE)is a rare but catastrophic vascular emergency characterized by acute occlusion of the aortic bifurcation,leading to bilateral lower limb ischemia and multiorgan dysfunction.Despite advances in imaging and surgical techniques,ASE has high morbidity and mortality rates,particularly when diagnosis or intervention is delayed.Here,we report two patients admitted to our center to increase awareness among emergency physicians.
基金the National Natural Science Foundation of China(82470675,82270671,81970555,82400752,82300731,82200714)the Xinyi Digestive Disease Research Fund(KY-2023-03-01)the Songjiang District Science and Technology Research Project(22SJKJGG27).
文摘Hypertriglyceridemia(HTG)is a common and significant contributor to acute pancreatitis(AP).Caffeine has been reported to have a protective effect against pancreatic disorders.However,the role of caffeine in hypertriglyceridemia acute pancreatitis(HAP)is still unknown.To investigate a new understanding of the relationship between caffeine and gut microbiota in HAP development.Using multi-omics analysis of 71 HAP and HTG patients,their characteristics of intestinal microecology were detected.HTG mice models were established through either pharmacological induction(P-407 intraperitoneal injection)or genetic ablation of GPIHBP1(GPIHBP1^(−/−)).Genes deferentially expressed in the gut were identified by RNA sequencing and the role of caffeine in reshaping gut microbial networks was investigated.Caffeine levels decreased significantly in HAP patients and were inversely correlated with the severity of HAP.Caffeine maintained the intestinal homeostasis and attenuated HAP through a gut microbiota-dependent manner in the mouse model.Specially,the commensal Faecalibacterium prausnitzii,which contributed most in distinguishing the differences between HTG and HAP patients,has been found to be related to the effect of caffeine on alleviating HAP.RNA sequencing combined with TLR4^(−/−)mice revealed that TLR4/NLRP3 may be the key signaling pathway for caffeine to maintain intestinal homeostasis and alleviating HAP.This study reveals the gut metabolites and microbiota characteristics of HAP and HTG patients,and explores the therapeutic potential of caffeine against HAP from the perspective of gut microbiota.
基金Supported by the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,No.CX2023021.
文摘Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.
基金supported by the special fund of the National Clinical Key Specialty Construction Program[(2022)301-2305].
文摘BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suitable for rapid clinical application.METHODS:In this multi-center retrospective cohort study,AAS patient data from three hospitals were analyzed.The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region,with Peking University Third Hospital data serving as the external test set.Four machine learning algorithms—logistic regression(LR),multilayer perceptron(MLP),Gaussian naive Bayes(GNB),and random forest(RF)—were used to develop predictive models based on 34 early-accessible clinical variables.A simplifi ed model was then derived based on fi ve key variables(Stanford type,pericardial eff usion,asymmetric peripheral arterial pulsation,decreased bowel sounds,and dyspnea)via Least Absolute Shrinkage and Selection Operator(LASSO)regression to improve ED applicability.RESULTS:A total of 929 patients were included in the modeling cohort,and 210 were included in the external test set.Four machine learning models based on 34 clinical variables were developed,achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85,respectively.The simplifi ed model incorporating fi ve key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78,respectively.Both models showed robust calibration and predictive stability across datasets.CONCLUSION:Both kinds of models were built based on machine learning tools,and proved to have certain prediction performance and extrapolation.
文摘Currently, glucocorticoids are the only treatment option for acute gout attacks in patients with chronic kidney disease (CKD) and progressive renal dysfunction. Management becomes particularly challenging when steroid therapy is contraindicated, poorly tolerated, or ineffective. IL-1β monoclonal antibodies offer potent, targeted anti-inflammatory effects and have been approved for the treatment of gout, providing new therapeutic hope for this population. Here, we report a case of a patient with CKD and progressively worsening renal function who experienced an acute gout attack requiring dialysis. Treatment with the IL-1β monoclonal antibody Firsekibart produced rapid and remarkable anti-inflammatory and analgesic effects, effectively controlling the gout attack, improving renal function, and allowing discontinuation of dialysis.
基金supported by the Scientific Research Project of the Health Commission of Shanxi Province(No.2024003)。
文摘This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to age-related immune dysfunction,whereas EEN has been demonstrated to improve clinical prognosis,reduce infection and complication rates,and shor ten hospital stays.However,ongoing debates exist regarding the optimal timing,route selection,and complication management of EEN.Through a systematic review of the literature,this study synthesizes current evidence on EEN in elderly SAP populations,critically examines unresolved clinical controversies,and proposes future research priorities to inform evidence-based practice.
文摘BACKGROUND:Acute pain is a sudden experience secondary to injuries and varies in perception among individuals.In trauma patients,it can negatively aff ect respiratory function,immune response,and wound healing,making it a signifi cant public health concern.This study is to determine the prevalence and factors associated with acute pain among emergency trauma patients.METHODS:A multicenter cross-sectional study was conducted.Data were collected via interviewer-administered questionnaires and patient chart review.The data were analyzed via the statistical package for social science version 25.Bivariable and multivariable logistic regression analyses were used.Variables with a P-value<0.05 were considered statistically signifi cant.RESULTS:A total of 397 patients were included in the study,for a response rate of 96.8%.The prevalence of pain during admission was 91.9%(95%confi dence intervals[95%CIs]:88.8%-94.4%).Blunt trauma(adjusted odds ratio[aOR]=2.82;95%CI:1.23-6.45),analgesia before admission to the emergency department(aOR=2.71;95%CI:1.16-6.36),documentation of pain severity in the chart(aOR=2.71;95%CI:1.16-6.36),analgesia provided within two hours after admission(aOR=7.60;95%CI:2.79-20.68),use of non-pharmacological pain management methods(aOR=3.09;95%CI:1.35-7.08)and availability of analgesia(aOR=3.95;95%CI:1.36-11.43)were associated with acute pain experience.CONCLUSION:The prevalence of acute pain among emergency trauma patients was high in the study area.Analgesia should be administered prior to admission,and non-pharmacological pain management should be implemented.Moreover,training on pain assessment and management should be provided for healthcare providers in the emergency department.
基金supported by Hebei Province Natural Science Foundation(H2023423037)The Government Funded Clinical Program of Hebei Province(No.ZF2025287)+1 种基金Special Project of Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation(No.YJY2024001)Chinese Medicine Scientific Research Program of Hebei Province(No.2025222).
文摘Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.
基金supported by the National Natural Science Foundation of China(No.82360120)the Kunming Medical University Joint Special Project on Applied Basic Research(202401AY070001-134),and project iGandanF-1082022-RGG049+2 种基金the Open Project of Yunnan Provincial Clinical Medical Center for Digestive System Diseases(2022LCZXXF-XH07/17)the 14th Undergraduate Scientific Research Project of Mudanjiang Medical University(2024057)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04).
文摘Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
基金Supported by The Central Public-Interest Scientific Institution Basal Research Fund,CAFS(2025XT0902)Earmarked for China Agriculture Research System(CARS-46).
文摘The widespread use of herbicides such as glyphosate isopropyl amine salt(GIS)and atrazine(ATZ)poses significant risks to aquatic ecosystems.This study investigated the single and joint acute toxicity of a 1:1 GIS-ATZ mixture on zebrafish(Danio rerio).Acute tests determined 96-h LC_(50) values of 123.41 mg/L for GIS and 103.95 mg/L for ATZ.In the joint toxicity test,these values decreased to 60.96 and 50.88 mg/L,respectively.The Additive Index(AI)analysis revealed a consistent synergistic interaction between the herbicides at all exposure intervals.These findings underscore the enhanced ecological threat of herbicide mixtures and highlight the necessity of considering joint effects in environmental risk assessments.
基金supported by the National Natural Science Foundation of China(No.82100164,82302692)the Capital Medical University Research Cultivation Fund(No.PYZ22099)the Guangdong Provincial Medical Science and Technology Research Fund Project(No.A2024190).
文摘Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.
基金supported by the Key Program of the National Natural Science Foundation of China(32230059)the Basic Science Center Program(T2288102)+3 种基金the Foundation of Frontiers Sciesnce Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the National Natural Science Foundation of China(32401128)the Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251)。
文摘Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.
基金supported by grants from the Health Commission of Zigong High-Level Talent Development Project(WJW-GCCRC007).
文摘Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.Methods:Sprague-Dawley rats were randomly divided into four groups:control,cisplatin,cisplatin+GP-17,and GP-17 alone.Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury,while GP-17 was given orally at 40 mg/kg/day for 7 d.The levels of serum creatinine and blood urea nitrogen,superoxide dismutase activity,and malondialdehyde content were measured.Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury.Moreover,the expression of mitophagy-related proteins,including PINK1,Parkin,LC3,and p62,and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays.Furthermore,human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17,with or without PINK1 siRNA transfection.Cell viability,apoptosis,reactive oxygen species levels,mitochondrial membrane potential,and the protein expression associated with the PINK1/Parkin pathway were measured.Results:In rats with cisplatin-induced acute kidney injury,GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen,attenuated tubular damage and mitochondrial ultrastructural injury,and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content.GP-17 further upregulated the protein levels of PINK1,Parkin,and LC3-Ⅱ/Ⅰratio while promoting p62 degradation,indicating enhanced mitophagic flux.In HK-2 cells,GP-17(20μM)co-treatment markedly attenuated cisplatin-induced cytotoxicity,apoptosis,reactive oxygen species overproduction,and mitochondrial depolarization.However,all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.Conclusions:GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy,which facilitates the clearance of damaged mitochondria,alleviates oxidative stress,and inhibits renal cell apoptosis.These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.
文摘Objective:To investigate the effect of“72-hour proactive follow-up”led by respiratory specialist nurses on reducing the 30-day readmission rate in patients with acute exacerbation of chronic obstructive pulmonary disease(COPD)after hospital discharge.Methods:A randomized controlled trial was conducted involving 60 patients with acute exacerbation of COPD admitted from September 2024 to September 2025.The participants were divided into a control group and an observation group,with 30 individuals in each group.The control group received routine discharge guidance nursing measures,including instructions on medication use,key points for condition monitoring,and scheduling of follow-up appointments.The observation group implemented“72-hour proactive follow-up”nursing measures,which included telephone follow-up within 72 hours after discharge,quantitative assessment of respiratory symptoms,dynamic adjustment of medication regimens,and personalized health education.The 30-day readmission rate,mMRC dyspnea index,CAT quality of life score,and other parameters were compared between the two groups.Results:The 30-day readmission rate in the observation group was significantly lower than that in the control group(p<0.05).The mMRC dyspnea index(1.8±0.5)in the observation group was significantly lower than that in the control group(2.5±0.7)(p<0.05).The CAT quality of life score(18.2±3.1)in the observation group was significantly higher than that in the control group(22.4±4.2)(p<0.05).The patient satisfaction score(92.5±4.3)in the observation group was higher than that in the control group(85.6±5.8)(p<0.05).Conclusion:The“72-hour proactive follow-up”nursing intervention demonstrates a favorable effect in reducing readmission rates,exhibiting significant clinical practical value.It can optimize the allocation of medical resources,effectively enhance patients’self-management efficacy,and holds prominent value for clinical promotion and application.
文摘AIM:To investigate the long-term outcomes in acute primary angle closure(APAC)patients treated with lens extraction(LE)surgery and to identify risk factors for glaucomatous optic neuropathy(GON).METHODS:In this longitudinal observational study,detailed medical histories of APAC patients and comprehensive ophthalmic examinations at final followup were collected.Logistic regression analysis was performed to identify predictors of blindness.Univariate and multivariate linear regression analyses were conducted to determine risk factors associated with visual outcomes.RESULTS:This study included 39 affected eyes of 31 subjects(26 females)with an average age of 74.1±8.0y.At 6.7±4.2y after APAC attack,2(5.7%)eyes had bestcorrected visual acuity(VA)worse than 3/60.Advanced glaucomatous visual field loss was observed in 15(39.5%)affected eyes and 5(25.0%)fellow eyes.Nine affected eyes(23.7%)had GON,and 11(28.9%)were blind.Six(15.4%)affected eyes and 2(9.1%)fellow eyes had suspicious progression.A significantly higher blindness rate in factory workers compared to office workers.Logistic regression identified that worse VA at attack(OR 10.568,95%CI 1.288-86.695;P=0.028)and worse early postoperative VA(OR 13.214,95%CI 1.157-150.881;P=0.038)were risk factors for blindness.Multivariate regression showed that longer duration of elevated intraocular pressure(P=0.004)and worse early postoperative VA(P=0.009)were associated with worse visual outcomes.CONCLUSION:Despite LE surgery,some APAC patients experience continued visual function deterioration.Lifelong monitoring is necessary.Target pressure and progression rates should be re-evaluated during follow-up.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
