Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechan...Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.展开更多
In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussiv...In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.展开更多
BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(I...BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.展开更多
In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excess...In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.展开更多
Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring...Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.展开更多
Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in I...Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.展开更多
BACKGROUND Immune checkpoint inhibitors(ICIs)are therapeutic agents for advanced and metastatic non-small cell lung cancer(NSCLC)with high clinical antitumor efficacy.However,immune-related adverse events occur in 20%...BACKGROUND Immune checkpoint inhibitors(ICIs)are therapeutic agents for advanced and metastatic non-small cell lung cancer(NSCLC)with high clinical antitumor efficacy.However,immune-related adverse events occur in 20%of these patients and often requiring treatment with immunosuppressive agents,such as corticosteroids.Consequently,this may increase the risk of patients to opportunistic infections.Pneumocystis jirovecii pneumonia(PJP),a rare but serious opportunistic infection typically observed in patients with human immunodeficiency virus,can also occur in cancer patients undergoing long-term glucocorticoid treatment.CASE SUMMARY We report a case of a 56-year-old male with squamous NSCLC treated with triplimab combined with paclitaxel,carboplatin,and radical thoracic radiation therapy.Following this regimen,he developed acute kidney injury(AKI)with elevated creatinine levels.After concurrent radical chemoradiotherapy ended,he developed a grade 3 immune-related AKI.High-dose corticosteroids were administered to treat AKI,and renal function gradually recovered.Corticosteroids were reduced to a dose of 10 mg prednisone equivalent daily eight weeks later;however,he developed severe pneumonia with spontaneous pneumothorax.Next-generation sequencing of the bronchoscopic lavage revealed PJP co-infection with herpes simplex virus 1 and cytomegalovirus.The inflammation was more severe in areas exposed to radiation.Piperacillin-tazobactam,acyclovir,sulfamethoxazole,and trimethoprim were used to control the infection.The patient recovered,and immunotherapy was terminated.CONCLUSION PJP is rare but can occur in patients with ICI adverse events and should be differentiated from tumor progression or immune-related adverse events.Thoracic radiation may increase risk,necessitating careful monitoring and prevention.展开更多
Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to lo...Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to longer in-hospital stay and increased short and long-term mortality.Its pathophysiology,although not well-established,revolves around medullary hypoxia paired with the direct toxicity of the substance to the kidney.Critically ill patients,as well as those with pre-existing renal disease and cardiovascular comorbidities,are more susceptible to CI-AKI.Despite the continuous research in the field of CI-AKI prevention,clinical practice is based mostly on periprocedural hydration.In this review,all the investigated methods of prevention are presented,with an emphasis on the latest evidence regarding the potential of RenalGuard and contrast removal systems for CI-AKI prevention in high-risk individuals.展开更多
BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as ...BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as renal failure.Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019(COVID-19).When presented with acute kidney injury(AKI),rhabdomyolysis may be related to higher morbidity and mortality.AIM To compare rhabdomyolysis-related AKI with other AKIs during COVID-19.METHODS A total of 115 patients with COVID-19 who had AKI were evaluated retrospec-tively.Fifteen patients had a definite diagnosis of rhabdomyolysis(i.e.,creatine kinase levels increased to>5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase).These patients were aged 61.0±19.1 years and their baseline creatinine levels were 0.87±0.13 mg/dL.Patients were treated according to national COVID-19 treatment guidelines.They were compared with patients with COVID-19 who had AKI due to other reasons.RESULTS For patients with rhabdomyolysis,creatinine reached 2.47±1.17 mg/dL during follow-up in hospital.Of these patients,13.3%had AKI upon hospital admission,and 86.4%developed AKI during hospital follow-up.Their peak C-reactive protein reached as high as 253.2±80.6 mg/L and was higher than in patients with AKI due to other reasons(P<0.01).Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis(P=0.02 and P=0.002,respective-ly).The mortality of patients with rhabdomyolysis was calculated as 73.3%,which was higher than in other patients with AKI(18.1%)(P=0.001).CONCLUSION Rhabdomyolysis was present in 13.0%of the patients who had AKI during COVID-19 infection.Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.展开更多
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
Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacolog...Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.展开更多
Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been dif...Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been difficult because of the uncertainty of the consequences of doing so, and the absence of publications to help determine whether revaccination may be considered safe or not. Purpose: We present a case report of a 59-year-old Canadian man who developed severe acute kidney injury associated with moderate proteinuria following his first COVID-19 vaccine with the Moderna vaccine (an mRNA vaccine). He required haemodialysis for 2 weeks, which was initiated when his creatinine reached 1002 μmol/l. A kidney biopsy showed changes consistent with acute tubular necrosis. The patient was cautioned that repeat vaccination might result in further kidney injury which might be irreversible. However, he badly wanted to attempt a second COVID-19 vaccination, to facilitate a family vacation across several countries in Europe, at a time when travel restrictions were in place in many countries for persons who had not completed a course of vaccines. Method: Following deliberations, the patient chose to try a different type of Covid-19 vaccine. On this occasion, he was vaccinated with the Novavax vaccine (a subunit COVID-19 vaccine). Following this, close monitoring of his urine to detect proteinuria and blood testing for acute kidney injury were carried out on days 1, 3, 7, and 60 after vaccination. Furthermore, a year after his repeat vaccination, his kidney function and urinalysis were again assessed. Result and Conclusions: The patient did not develop acute kidney injury or worsening proteinuria following repeat vaccination. It remains unclear if acute kidney injury with proteinuria is caused by Covid-19 vaccination, or simply an incidental association. This case report suggests that it is may be reasonable for patients with acute kidney injury after COVID-19 vaccination to consider trying a different type of vaccine. In situations where a new virulent strain of virus emerges or in patients at risk of severe complication from infection, it may be reasonable to consider revaccination following appropriate counselling with close monitoring of renal function.展开更多
BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are...BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.展开更多
BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is curre...BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB.Levels of copper ion,lactate,glucose,heat shock protein-70(HSP-70),and dihydrolipoamide dehydrogenase(DLAT)were determined.A diabetic rat model was established and CPB was performed.The rats were assessed for the development of CPB-AKI,and for the association of AKI with cuproptosis by detecting copper levels,iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.RESULTS CPB resulted in elevations of copper,lactate,HSP-70 and DLAT in blood and urine in both diabetic and nondiabetic patients.CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats.Cuproptosis-related proteins also appeared to be significantly reduced.CONCLUSION CPB-AKI is associated with cuproptosis.Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.展开更多
Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulatio...Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.展开更多
Contrast-induced acute kidney injury(CI-AKI)is a major concern in clinical practice,particularly among high-risk patients with preexisting renal and cardiovascular conditions.Although periprocedural hydration has long...Contrast-induced acute kidney injury(CI-AKI)is a major concern in clinical practice,particularly among high-risk patients with preexisting renal and cardiovascular conditions.Although periprocedural hydration has long been the primary approach for CI-AKI prevention,recent advancements have led to the development of novel approaches such as RenalGuard and contrast removal systems.This editorial explores these emerging approaches and highlights their potential for enhancing CI-AKI prevention.By incorporating the latest evidence into clinical practice,health-care professionals can more effectively maintain renal function and improve outcomes for patients undergoing contrast-enhanced procedures.展开更多
BACKGROUND Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome(ACS).Troponin levels in ACS patients can often be more than...BACKGROUND Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome(ACS).Troponin levels in ACS patients can often be more than 50 times the upper reference limit.Some patients with subarachnoid hemorrhage(SAH)also show electrocardiogram abnormalities,myocardial damage,and elevated cardiac biomarkers.Unlike ACS patients,patients with SAH only have a slight increase in troponin,and the use of anticoagulants or antiplatelet drugs is prohibited.Because of the opposite treatment modalities,it is essential for clinicians to distinguish between SAH and ACS.CASE SUMMARY A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain.The final diagnosis was intraspinal hematoma in the thoracic spine.We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope.Intraoperatively,diffuse hematoma formation was found in the T7-T10 spinal canal,and no obvious spinal vascular malformation changes were observed.Postoperative head and spinal magnetic resonance imaging(MRI)showed a small amount of SAH in the skull,no obvious abnormalities in the cervical and thoracic spinal canals,and no abnormal signals in the lumbar spinal canal.Thoracoab-dominal aorta computed tomography angiography showed no vascular malfor-mation.Postoperative motor system examination showed Medical Research Council Scale grade 1/5 strength in both lower extremities,and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3.CONCLUSION Extremely elevated troponin levels(more than 50 times the normal range)are not unique to coronary artery disease.SAH can also result in extremely high troponin levels,and antiplatelet drugs are contraindicated in such cases.Emergency MRI can help in the early differential diagnosis,as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontaneous spinal SAH.展开更多
BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question...BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question is“How does the use of opioid medications in pain management,compared with non-opioid medications,affect pain intensity over the short,intermediate,and long-term in adults with acute traumatic pain?”.METHODS The protocol was prospectively registered on the International Prospective Re-gister of Systematic Reviews:CRD42021279639.Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full,with the PICO framework:P:Adult patients with traumatic injuries,I:Opioid medications,C:Non-opioid medi-cations,O:A minimum clinically important difference(MCID)in pain.RESULTS After full-text screening,we included 14 studies in the qualitative synthesis.Of these 14 studies,12 were rando-mized clinical trials(RCTs)and 2 were pseudo-RCTs with a total of 2347 patients enrolled.There was heteroge-neity in both medication utilized and outcome in these studies;only two studies were homogeneous regarding the type of study conducted,the opioid used,its comparator,and the outcome explored.The MCID was evaluated in 8 studies,while in 6 studies,any measured pain reduction was considered as an outcome.In 11 cases,the setting of care was the Emergency Department;in 2 cases,care occurred out-of-hospital;and in one case,the setting was not well-specified.The included studies were found to have a low-moderate risk of bias.CONCLUSION Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury.Intravenous ketamine may cause more adverse events than other routes of administration.展开更多
BACKGROUND The prognosis of critically ill patients is closely linked to their gastrointestinal(GI)function.The acute GI injury(AGI)grading system,established in 2012,is extensively utilized to evaluate GI dysfunction...BACKGROUND The prognosis of critically ill patients is closely linked to their gastrointestinal(GI)function.The acute GI injury(AGI)grading system,established in 2012,is extensively utilized to evaluate GI dysfunction and forecast outcomes in clinical settings.In 2021,the GI dysfunction score(GIDS)was developed,building on the AGI grading system,to enhance the accuracy of GI dysfunction severity assessment,improve prognostic predictions,reduce subjectivity,and increase reproducibility.AIM To compare the predictive capabilities of GIDS and the AGI grading system for 28-day mortality in critically ill patients.METHODS A retrospective study was conducted at the general intensive care unit(ICU)of a regional university hospital.All data were collected during the first week of ICU admission.The primary outcome was 28-day mortality.Multivariable logistic regression analyzed whether GIDS and AGI grade were independent risk factors for 28-day mortality.The predictive abilities of GIDS and AGI grade were compared using the receiver operating characteristic curve,with DeLong’s test assessing differences between the curves’areas.RESULTS The incidence of AGI in the first week of ICU admission was 92.13%.There were 85 deaths(47.75%)within 28 days of ICU admission.There was no initial 24-hour difference in GIDS between the non-survival and survival groups.Both GIDS(OR 2.01,95%CI:1.25-3.24;P=0.004)and AGI grade(OR 1.94,95%CI:1.12-3.38;P=0.019)were independent predictors of 28-day mortality.No significant difference was found between the predictive accuracy of GIDS and AGI grade for 28-day mortality during the first week of ICU admission(Z=-0.26,P=0.794).CONCLUSION GIDS within the first 24 hours was an unreliable predictor of 28-day mortality.The predictive accuracy for 28-day mortality from both systems during the first week was comparable.展开更多
Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria ...Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.展开更多
基金supported by the tenth batch of"3221"industrial innovation and scientific research projects in Bengbu City(beng talent[2020]No.8)the 2021 Bengbu Medical College Science and Technology Project[Natural Science,Project Number:2021byzd217].
文摘Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.
基金the National Natural Science Foundation(81773982,82003937)Youth Academic leaders of the Qinglan Project in Jiangsu province for financial support。
文摘In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.
文摘BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.
基金Yunnan Fundamental Research Projects(202201AU070167,202301AT070258)Yunnan Key Laboratory of Formulated Granules(202105AG070014).
文摘In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.
基金supported by the Construction Project of Tu Jinwen National Chinese Medical Master Inheritance Studio of National Administration of Traditional Chinese Medicine(National TCMEducation Letter[2022]No.245)Hubei Province Public Health Youth Top Talents Training Program(Hubei Health Notice[2021]No.74).
文摘Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.
基金supported by the National Natural Science Foundation of China(No.82104581,No.82060864).
文摘Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.
基金Supported by Shandong Natural Science Foundation,No.ZR2021QH034China Postdoctoral Science Foundation,No.2023M731305.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)are therapeutic agents for advanced and metastatic non-small cell lung cancer(NSCLC)with high clinical antitumor efficacy.However,immune-related adverse events occur in 20%of these patients and often requiring treatment with immunosuppressive agents,such as corticosteroids.Consequently,this may increase the risk of patients to opportunistic infections.Pneumocystis jirovecii pneumonia(PJP),a rare but serious opportunistic infection typically observed in patients with human immunodeficiency virus,can also occur in cancer patients undergoing long-term glucocorticoid treatment.CASE SUMMARY We report a case of a 56-year-old male with squamous NSCLC treated with triplimab combined with paclitaxel,carboplatin,and radical thoracic radiation therapy.Following this regimen,he developed acute kidney injury(AKI)with elevated creatinine levels.After concurrent radical chemoradiotherapy ended,he developed a grade 3 immune-related AKI.High-dose corticosteroids were administered to treat AKI,and renal function gradually recovered.Corticosteroids were reduced to a dose of 10 mg prednisone equivalent daily eight weeks later;however,he developed severe pneumonia with spontaneous pneumothorax.Next-generation sequencing of the bronchoscopic lavage revealed PJP co-infection with herpes simplex virus 1 and cytomegalovirus.The inflammation was more severe in areas exposed to radiation.Piperacillin-tazobactam,acyclovir,sulfamethoxazole,and trimethoprim were used to control the infection.The patient recovered,and immunotherapy was terminated.CONCLUSION PJP is rare but can occur in patients with ICI adverse events and should be differentiated from tumor progression or immune-related adverse events.Thoracic radiation may increase risk,necessitating careful monitoring and prevention.
文摘Contrast-induced acute kidney injury(CI-AKI)is the third leading cause of acute kidney injury deriving from the intravascular administration of contrast media in diagnostic and therapeutic procedures and leading to longer in-hospital stay and increased short and long-term mortality.Its pathophysiology,although not well-established,revolves around medullary hypoxia paired with the direct toxicity of the substance to the kidney.Critically ill patients,as well as those with pre-existing renal disease and cardiovascular comorbidities,are more susceptible to CI-AKI.Despite the continuous research in the field of CI-AKI prevention,clinical practice is based mostly on periprocedural hydration.In this review,all the investigated methods of prevention are presented,with an emphasis on the latest evidence regarding the potential of RenalGuard and contrast removal systems for CI-AKI prevention in high-risk individuals.
文摘BACKGROUND Viral and bacterial infections may be complicated by rhabdomyolysis,which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnor-malities to life-threatening conditions such as renal failure.Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019(COVID-19).When presented with acute kidney injury(AKI),rhabdomyolysis may be related to higher morbidity and mortality.AIM To compare rhabdomyolysis-related AKI with other AKIs during COVID-19.METHODS A total of 115 patients with COVID-19 who had AKI were evaluated retrospec-tively.Fifteen patients had a definite diagnosis of rhabdomyolysis(i.e.,creatine kinase levels increased to>5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase).These patients were aged 61.0±19.1 years and their baseline creatinine levels were 0.87±0.13 mg/dL.Patients were treated according to national COVID-19 treatment guidelines.They were compared with patients with COVID-19 who had AKI due to other reasons.RESULTS For patients with rhabdomyolysis,creatinine reached 2.47±1.17 mg/dL during follow-up in hospital.Of these patients,13.3%had AKI upon hospital admission,and 86.4%developed AKI during hospital follow-up.Their peak C-reactive protein reached as high as 253.2±80.6 mg/L and was higher than in patients with AKI due to other reasons(P<0.01).Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis(P=0.02 and P=0.002,respective-ly).The mortality of patients with rhabdomyolysis was calculated as 73.3%,which was higher than in other patients with AKI(18.1%)(P=0.001).CONCLUSION Rhabdomyolysis was present in 13.0%of the patients who had AKI during COVID-19 infection.Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.
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.
基金supported by the National Key R&D Program of China(2023YFB3507004)National Natural Science Foundation of China(U21A20148)+5 种基金International Partnership Program of Chinese Academy of Sciences(116134KYSB20210052)Anhui Provincial Natural Science Foundation(2308085QE183,2308085QE181)CASHIPS Director’s Fund(YZJJ2024QN44,YZJJ2023QN43)Heye Health Technology Chong Ming Project(HYCMP2021010)China Post-doctoral Science Foundation(2023M743536)Science Research Fund for Postdoctoral in Anhui Province(2023B669)。
文摘Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.
文摘Background: Acute kidney injury associated with proteinuria has been reported following vaccination against SARS-CoV-2 several times since 2021. Decisions about subsequent revaccination in these patients have been difficult because of the uncertainty of the consequences of doing so, and the absence of publications to help determine whether revaccination may be considered safe or not. Purpose: We present a case report of a 59-year-old Canadian man who developed severe acute kidney injury associated with moderate proteinuria following his first COVID-19 vaccine with the Moderna vaccine (an mRNA vaccine). He required haemodialysis for 2 weeks, which was initiated when his creatinine reached 1002 μmol/l. A kidney biopsy showed changes consistent with acute tubular necrosis. The patient was cautioned that repeat vaccination might result in further kidney injury which might be irreversible. However, he badly wanted to attempt a second COVID-19 vaccination, to facilitate a family vacation across several countries in Europe, at a time when travel restrictions were in place in many countries for persons who had not completed a course of vaccines. Method: Following deliberations, the patient chose to try a different type of Covid-19 vaccine. On this occasion, he was vaccinated with the Novavax vaccine (a subunit COVID-19 vaccine). Following this, close monitoring of his urine to detect proteinuria and blood testing for acute kidney injury were carried out on days 1, 3, 7, and 60 after vaccination. Furthermore, a year after his repeat vaccination, his kidney function and urinalysis were again assessed. Result and Conclusions: The patient did not develop acute kidney injury or worsening proteinuria following repeat vaccination. It remains unclear if acute kidney injury with proteinuria is caused by Covid-19 vaccination, or simply an incidental association. This case report suggests that it is may be reasonable for patients with acute kidney injury after COVID-19 vaccination to consider trying a different type of vaccine. In situations where a new virulent strain of virus emerges or in patients at risk of severe complication from infection, it may be reasonable to consider revaccination following appropriate counselling with close monitoring of renal function.
文摘BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.
基金Supported by the Natural Science Foundation of Heilongjiang Province,No.LH2022H035the First Affiliated Hospital of Harbin Medical University Foundation,No.2024JQ14.
文摘BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB.Levels of copper ion,lactate,glucose,heat shock protein-70(HSP-70),and dihydrolipoamide dehydrogenase(DLAT)were determined.A diabetic rat model was established and CPB was performed.The rats were assessed for the development of CPB-AKI,and for the association of AKI with cuproptosis by detecting copper levels,iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.RESULTS CPB resulted in elevations of copper,lactate,HSP-70 and DLAT in blood and urine in both diabetic and nondiabetic patients.CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats.Cuproptosis-related proteins also appeared to be significantly reduced.CONCLUSION CPB-AKI is associated with cuproptosis.Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.
基金This work was supported by the National Natural Science Foundation of China(82071779 and 81901626)the Science Fund for Creative Research Groups of Chongqing Municipal Education Commission of China,the grants from the Talent Foundation of Army Medical University(to Shuang-Shuang Dai)+1 种基金the Scientific Research Grant(ALJ22J003)the Chongqing Natural Science Foundation of China(CSTB2022NSCQ-MSX0177).
文摘Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.
文摘Contrast-induced acute kidney injury(CI-AKI)is a major concern in clinical practice,particularly among high-risk patients with preexisting renal and cardiovascular conditions.Although periprocedural hydration has long been the primary approach for CI-AKI prevention,recent advancements have led to the development of novel approaches such as RenalGuard and contrast removal systems.This editorial explores these emerging approaches and highlights their potential for enhancing CI-AKI prevention.By incorporating the latest evidence into clinical practice,health-care professionals can more effectively maintain renal function and improve outcomes for patients undergoing contrast-enhanced procedures.
文摘BACKGROUND Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome(ACS).Troponin levels in ACS patients can often be more than 50 times the upper reference limit.Some patients with subarachnoid hemorrhage(SAH)also show electrocardiogram abnormalities,myocardial damage,and elevated cardiac biomarkers.Unlike ACS patients,patients with SAH only have a slight increase in troponin,and the use of anticoagulants or antiplatelet drugs is prohibited.Because of the opposite treatment modalities,it is essential for clinicians to distinguish between SAH and ACS.CASE SUMMARY A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain.The final diagnosis was intraspinal hematoma in the thoracic spine.We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope.Intraoperatively,diffuse hematoma formation was found in the T7-T10 spinal canal,and no obvious spinal vascular malformation changes were observed.Postoperative head and spinal magnetic resonance imaging(MRI)showed a small amount of SAH in the skull,no obvious abnormalities in the cervical and thoracic spinal canals,and no abnormal signals in the lumbar spinal canal.Thoracoab-dominal aorta computed tomography angiography showed no vascular malfor-mation.Postoperative motor system examination showed Medical Research Council Scale grade 1/5 strength in both lower extremities,and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3.CONCLUSION Extremely elevated troponin levels(more than 50 times the normal range)are not unique to coronary artery disease.SAH can also result in extremely high troponin levels,and antiplatelet drugs are contraindicated in such cases.Emergency MRI can help in the early differential diagnosis,as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontaneous spinal SAH.
文摘BACKGROUND The use of opioids for pain is linked to an increased risk of developing opioid use disorder,and has resulted in the emergence of the opioid crisis over the last few years.AIM The systematic review question is“How does the use of opioid medications in pain management,compared with non-opioid medications,affect pain intensity over the short,intermediate,and long-term in adults with acute traumatic pain?”.METHODS The protocol was prospectively registered on the International Prospective Re-gister of Systematic Reviews:CRD42021279639.Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full,with the PICO framework:P:Adult patients with traumatic injuries,I:Opioid medications,C:Non-opioid medi-cations,O:A minimum clinically important difference(MCID)in pain.RESULTS After full-text screening,we included 14 studies in the qualitative synthesis.Of these 14 studies,12 were rando-mized clinical trials(RCTs)and 2 were pseudo-RCTs with a total of 2347 patients enrolled.There was heteroge-neity in both medication utilized and outcome in these studies;only two studies were homogeneous regarding the type of study conducted,the opioid used,its comparator,and the outcome explored.The MCID was evaluated in 8 studies,while in 6 studies,any measured pain reduction was considered as an outcome.In 11 cases,the setting of care was the Emergency Department;in 2 cases,care occurred out-of-hospital;and in one case,the setting was not well-specified.The included studies were found to have a low-moderate risk of bias.CONCLUSION Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury.Intravenous ketamine may cause more adverse events than other routes of administration.
基金approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University(No.2024-KLS-369-02).
文摘BACKGROUND The prognosis of critically ill patients is closely linked to their gastrointestinal(GI)function.The acute GI injury(AGI)grading system,established in 2012,is extensively utilized to evaluate GI dysfunction and forecast outcomes in clinical settings.In 2021,the GI dysfunction score(GIDS)was developed,building on the AGI grading system,to enhance the accuracy of GI dysfunction severity assessment,improve prognostic predictions,reduce subjectivity,and increase reproducibility.AIM To compare the predictive capabilities of GIDS and the AGI grading system for 28-day mortality in critically ill patients.METHODS A retrospective study was conducted at the general intensive care unit(ICU)of a regional university hospital.All data were collected during the first week of ICU admission.The primary outcome was 28-day mortality.Multivariable logistic regression analyzed whether GIDS and AGI grade were independent risk factors for 28-day mortality.The predictive abilities of GIDS and AGI grade were compared using the receiver operating characteristic curve,with DeLong’s test assessing differences between the curves’areas.RESULTS The incidence of AGI in the first week of ICU admission was 92.13%.There were 85 deaths(47.75%)within 28 days of ICU admission.There was no initial 24-hour difference in GIDS between the non-survival and survival groups.Both GIDS(OR 2.01,95%CI:1.25-3.24;P=0.004)and AGI grade(OR 1.94,95%CI:1.12-3.38;P=0.019)were independent predictors of 28-day mortality.No significant difference was found between the predictive accuracy of GIDS and AGI grade for 28-day mortality during the first week of ICU admission(Z=-0.26,P=0.794).CONCLUSION GIDS within the first 24 hours was an unreliable predictor of 28-day mortality.The predictive accuracy for 28-day mortality from both systems during the first week was comparable.
文摘Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.