Background:Acute lateral ankle sprains(ALAS)are associated with long-term impairments and instability tied to altered neural excitability.Arthrogenic muscle inhibition(AMI)has been observed in this population;however,...Background:Acute lateral ankle sprains(ALAS)are associated with long-term impairments and instability tied to altered neural excitability.Arthrogenic muscle inhibition(AMI)has been observed in this population;however,relationships with injury-related impairments are unclear,potentially due to the resting,prone position in which AMI is typically measured.Assessing AMI during bipedal stance may provide a better understanding of this relationship.Methods:AMI was assessed in 38 young adults(19 ALAS within 72 h of injury:10 males,21.4±2.7 years;19 healthy controls:10 males,21.9±2.2 years;mean±SD)using the Hoffmann reflex(H-reflex)during bipedal stance.Electrical stimulation was administered to identify the _(max)imal H-reflex(H_(max))and _(max)imal motor response(M_(max))from the soleus,fibularis longus,and tibialis anterior muscles.The primary outcome measure was the H_(max)/M_(max) ratio.Secondary outcomes included acute symptoms(pain and swelling),postural control during bipedal stance,and self-reported function.Results:No significant group-by-limb interactions were observed for any muscle.However,a significant group main effect was observed in the soleus muscle(F(1,35)=6.82,p=0.013),indicating significantly lower H_(max)/M_(max) ratios following ALAS(0.38±0.20)compared to healthy controls(0.53±0.16).Furthermore,lower H_(max)/M_(max) ratios in the soleus significantly correlated with acute symptoms and self-reported function but not with postural control.Conclusion:This study supports previous evidence of AMI in patients with ALAS,providing insight into neurophysiologic impacts of musculoskeletal injury.Our results suggest that assessing AMI in a standing position following acute injury may provide valuable insight into how AMI develops and guide potential therapeutic options to curb and offset the formation of joint instability.展开更多
BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AG...BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AGI),but its specific mechanism is not completely understood,and few clinical reports are available.AIM To explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODS In our prospective clinical trial,48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment,whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin.AGI grade,sequential organ failure assessment score,acute physiology and chronic health evaluation II score,D-dimer,activated partial thromboplastin time(APTT),anti-Xa factor,interleukin-6,tumour necrosis factor-α,HPA,syndecan-1(SDC-1),LC3B(autophagy marker),intestinal fatty acid binding protein,D-lactate,motilin,gastrin,CD4/CD8,length of intensive care unit(ICU)stay,length of hospital stay and 28-d survival on the 1^(st),3^(rd) and 7^(th) d after treatment were compared.Correlations between HPA and AGI grading as well as LC3B were compared.Receiver operator characteristic(ROC)curves were generated to evaluate the diagnostic value of HPA,intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTS Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group(P<0.05).In addition,intestinal fatty acid-binding protein,D-lactate,AGI grade,motilin,and gastrin levels and sequential organ failure assessment score were significantly decreased(P<0.05)in the intervention group.However,LC3B,APTT,anti-Xa factor,and CD4/CD8 were significantly increased(P<0.05)in the intervention group.No significant differences in interleukin-6,tumour necrosis factor-α,d-dimer,acute physiology and chronic health evaluation II score,length of ICU stay,length of hospital stay,or 28-d survival were noted between the two groups(P>0.05).Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade.ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSION HPA has great potential as a diagnostic marker for S-AGI.Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms.The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.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
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
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 Acute injuries to the tibiofibular syndesmosis,often associated with high ankle sprains or malleolar fractures,require precise diagnosis and treatment to prevent long-term complications.This case report exp...BACKGROUND Acute injuries to the tibiofibular syndesmosis,often associated with high ankle sprains or malleolar fractures,require precise diagnosis and treatment to prevent long-term complications.This case report explores the use of needle arthroscopy as a minimally invasive technique for the repair of tibiofibular syndesmosis injuries.CASE SUMMARY We report on a 40-year-old male patient who presented with a trimalleolar fracture and ankle subluxation following a high ankle sprain.Due to significant swelling and poor soft tissue quality,initial management involved external stabilization.Subsequently,needle arthroscopy was employed to assess and treat the tibiofibular syndesmosis injury.The procedure,performed under spinal anesthesia and fluoroscopic control,included nanoscopic evaluation of the ankle joint and reduction of the syndesmosis using a suture button.Follow-up assessments showed significant improvement in pain levels,range of motion,and functional scores.At 26 weeks post-procedure,the patient achieved full range of motion and pain-free status.Needle arthroscopy offers a promising alternative for the management of acute tibiofibular syndesmosis injuries,combining diagnostic and therapeutic capabilities with minimal invasiveness.CONCLUSION This technique may enhance clinical outcomes and reduce recovery times,warranting further investigation and integration into clinical practice.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 Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(I...BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.展开更多
In the 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 The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(C...BACKGROUND The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(COVID-19),T2DM predisposed patients to ARDS,especially those who were on insulin at home.AIMTo evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes.METHODS We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database.Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus(DM)(IDDM)and non-insulindependent DM(NIDDM)groups.After applying exclusion criteria and matching over 20 variables,we compared cohorts for mortality,duration of mechanical ventilation,incidence of acute kidney injury(AKI),length of stay(LOS),hospitalization costs,and other clinical outcomes.RESULTS Following 1:1 propensity score matching,the analysis included 274 patients in each group.Notably,no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates(32.8%vs 31.0%,P=0.520),median hospital LOS(10 d,P=0.537),requirement for mechanical ventilation,incidence rates of sepsis,pneumonia or AKI,median total hospitalization costs,or patient disposition upon discharge.CONCLUSION Compared to alternative anti-diabetic medications,outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.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
Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear ...Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.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: 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
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
Objective:To observe the clinical efficacy of the Zhuang medicine Yingbupu decoction on stage I and II acute kidney injury through sequential test.Methods:The open one-way qualitative response sequential design of exp...Objective:To observe the clinical efficacy of the Zhuang medicine Yingbupu decoction on stage I and II acute kidney injury through sequential test.Methods:The open one-way qualitative response sequential design of experiments was adopted,and the patients with AKI in phase I and II who met the inclusion criteria were divided into the treatment group and the control group according to the order of hospitalization by random number table.On the basis of basic treatment,the treatment group was treated with Zhuang medicine Yingbupu decoction,and the control group was treated with Jinshuibao tablet.The clinical efficacy,TCM syndrome score,24 h urine volume,serum creatinine(Scr),microalbumin in urine(mAlb),neutrophil Gelatinase related lipid delivery albumin(NGAL)of the two groups were compared,and the adverse reactions and complications of the two groups were observed.Results:After 14 d of treatment,when the treatment group reached the 10th case,the experimental line contacted the upper bound U-line and reached the experimental standard to terminate the experiment.The effective hypothesis was accepted,and it was believed that the Zhuang medicine Yingbupu decoction had a therapeutic effect on stage I and II AKI.The conclusion was drawn that the treatment group received the Zhuang medicine Yingbupu.The clinical effective rate and improvement days were similar between the two groups,and there was no significant difference(P>0.05).However,the integral value of traditional Chinese medicine syndrome in the treatment group was lower than that in the control group(P<0.05),After treatment,the Scr,mAlb,and NGAL levels of patients in both groups were lower than before treatment(P<0.05).After treatment,the Scr,mAlb,and NGAL values in the treatment group were significantly lower than those in the control group(P<0.05).After treatment,the 24-hour urine volume in both groups was higher than that before treatment,and the values in the treatment group were significantly higher than those in the control group(P<0.05).During the treatment period,there were no significant adverse reactions or complications in either group.Conclusion:The Zhuang medicine Yingbupu decoction is effective in treating stage I and II AKI,and the Zhuang medicine Yingbupu can significantly improve the symptoms and quality of life of patients with stage I and II AKI.Its improvement of renal function is better than that of Jinshuibao tablets,and its safety is good.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
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
[Objectives]To systematically analyze the risk factors for acute kidney injury(AKI)in patients treated with antibiotics and to conduct a meta-analysis of published clinical studies.[Methods]PubMed,Web of Science,and E...[Objectives]To systematically analyze the risk factors for acute kidney injury(AKI)in patients treated with antibiotics and to conduct a meta-analysis of published clinical studies.[Methods]PubMed,Web of Science,and Embase were searched for relevant cohort and case-control studies from January 1,2001,to October 31,2022.Meta-analysis was performed using RevMan5.4 and StataMP15.[Results]A total of 22 studies were included.Regarding patient factors,serum creatinine(SCr;MD=1.03,95%CI of-0.07 to-0.02)was associated with increased antibiotic-associated AKI.Regarding the comorbidities and clinical factors,diabetes(OR=1.34,95%CI of 1.06 to 1.69,tumor(OR=2.07,95%CI of 1.13 to 3.79),pneumonia(OR=1.83,95%CI of 1.24 to 2.71),mechanical ventilation(OR=3.44,95%CI of 1.93 to 6.12),and ICU admission(OR=2.83,95%CI of 2.13 to 3.75)increased the risk of AKI in patients receiving antibiotic therapy.Regarding drug factors,diuretics(OR=2.76,95%CI of 2.16 to 3.52)increased the risk of antibiotic-associated AKI.[Conclusions]This paper may assist clinicians in predicting the risk factors for AKI in patients receiving antibiotic therapy.展开更多
文摘Background:Acute lateral ankle sprains(ALAS)are associated with long-term impairments and instability tied to altered neural excitability.Arthrogenic muscle inhibition(AMI)has been observed in this population;however,relationships with injury-related impairments are unclear,potentially due to the resting,prone position in which AMI is typically measured.Assessing AMI during bipedal stance may provide a better understanding of this relationship.Methods:AMI was assessed in 38 young adults(19 ALAS within 72 h of injury:10 males,21.4±2.7 years;19 healthy controls:10 males,21.9±2.2 years;mean±SD)using the Hoffmann reflex(H-reflex)during bipedal stance.Electrical stimulation was administered to identify the _(max)imal H-reflex(H_(max))and _(max)imal motor response(M_(max))from the soleus,fibularis longus,and tibialis anterior muscles.The primary outcome measure was the H_(max)/M_(max) ratio.Secondary outcomes included acute symptoms(pain and swelling),postural control during bipedal stance,and self-reported function.Results:No significant group-by-limb interactions were observed for any muscle.However,a significant group main effect was observed in the soleus muscle(F(1,35)=6.82,p=0.013),indicating significantly lower H_(max)/M_(max) ratios following ALAS(0.38±0.20)compared to healthy controls(0.53±0.16).Furthermore,lower H_(max)/M_(max) ratios in the soleus significantly correlated with acute symptoms and self-reported function but not with postural control.Conclusion:This study supports previous evidence of AMI in patients with ALAS,providing insight into neurophysiologic impacts of musculoskeletal injury.Our results suggest that assessing AMI in a standing position following acute injury may provide valuable insight into how AMI develops and guide potential therapeutic options to curb and offset the formation of joint instability.
基金the Science and Technology Department of Gansu Province,No.20JR5RA35Science and Technology Project of Gansu Province,No.22JR10KA009+1 种基金Talent Innovation and Entrepreneurship Project of Science and Technology Bureau of Chengguan District,Lanzhou,No.2020RCCX0030Lanzhou Science and Technology Development Guiding Plan Project,No.2019-ZD-37.
文摘BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AGI),but its specific mechanism is not completely understood,and few clinical reports are available.AIM To explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODS In our prospective clinical trial,48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment,whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin.AGI grade,sequential organ failure assessment score,acute physiology and chronic health evaluation II score,D-dimer,activated partial thromboplastin time(APTT),anti-Xa factor,interleukin-6,tumour necrosis factor-α,HPA,syndecan-1(SDC-1),LC3B(autophagy marker),intestinal fatty acid binding protein,D-lactate,motilin,gastrin,CD4/CD8,length of intensive care unit(ICU)stay,length of hospital stay and 28-d survival on the 1^(st),3^(rd) and 7^(th) d after treatment were compared.Correlations between HPA and AGI grading as well as LC3B were compared.Receiver operator characteristic(ROC)curves were generated to evaluate the diagnostic value of HPA,intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTS Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group(P<0.05).In addition,intestinal fatty acid-binding protein,D-lactate,AGI grade,motilin,and gastrin levels and sequential organ failure assessment score were significantly decreased(P<0.05)in the intervention group.However,LC3B,APTT,anti-Xa factor,and CD4/CD8 were significantly increased(P<0.05)in the intervention group.No significant differences in interleukin-6,tumour necrosis factor-α,d-dimer,acute physiology and chronic health evaluation II score,length of ICU stay,length of hospital stay,or 28-d survival were noted between the two groups(P>0.05).Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade.ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSION HPA has great potential as a diagnostic marker for S-AGI.Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms.The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.
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.
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.
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.
文摘BACKGROUND Acute injuries to the tibiofibular syndesmosis,often associated with high ankle sprains or malleolar fractures,require precise diagnosis and treatment to prevent long-term complications.This case report explores the use of needle arthroscopy as a minimally invasive technique for the repair of tibiofibular syndesmosis injuries.CASE SUMMARY We report on a 40-year-old male patient who presented with a trimalleolar fracture and ankle subluxation following a high ankle sprain.Due to significant swelling and poor soft tissue quality,initial management involved external stabilization.Subsequently,needle arthroscopy was employed to assess and treat the tibiofibular syndesmosis injury.The procedure,performed under spinal anesthesia and fluoroscopic control,included nanoscopic evaluation of the ankle joint and reduction of the syndesmosis using a suture button.Follow-up assessments showed significant improvement in pain levels,range of motion,and functional scores.At 26 weeks post-procedure,the patient achieved full range of motion and pain-free status.Needle arthroscopy offers a promising alternative for the management of acute tibiofibular syndesmosis injuries,combining diagnostic and therapeutic capabilities with minimal invasiveness.CONCLUSION This technique may enhance clinical outcomes and reduce recovery times,warranting further investigation and integration into clinical practice.
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.
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 The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(COVID-19),T2DM predisposed patients to ARDS,especially those who were on insulin at home.AIMTo evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes.METHODS We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database.Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus(DM)(IDDM)and non-insulindependent DM(NIDDM)groups.After applying exclusion criteria and matching over 20 variables,we compared cohorts for mortality,duration of mechanical ventilation,incidence of acute kidney injury(AKI),length of stay(LOS),hospitalization costs,and other clinical outcomes.RESULTS Following 1:1 propensity score matching,the analysis included 274 patients in each group.Notably,no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates(32.8%vs 31.0%,P=0.520),median hospital LOS(10 d,P=0.537),requirement for mechanical ventilation,incidence rates of sepsis,pneumonia or AKI,median total hospitalization costs,or patient disposition upon discharge.CONCLUSION Compared to alternative anti-diabetic medications,outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.
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Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01C604)。
文摘Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.
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: 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.
基金2021 Guangxi Famous Traditional Chinese Medicine Inheritance Studio Construction Project[Guizhong Medicine Science and Education Development(2021)No.6]Key Discipline of Personnel Training-Ethnic Medicine(Zhuang Medicine)(050220250102)Graduate Student Innovation and Entrepreneurship Project of Guangxi University of Traditional Chinese Medicine in 2021(YCXJ2021125)。
文摘Objective:To observe the clinical efficacy of the Zhuang medicine Yingbupu decoction on stage I and II acute kidney injury through sequential test.Methods:The open one-way qualitative response sequential design of experiments was adopted,and the patients with AKI in phase I and II who met the inclusion criteria were divided into the treatment group and the control group according to the order of hospitalization by random number table.On the basis of basic treatment,the treatment group was treated with Zhuang medicine Yingbupu decoction,and the control group was treated with Jinshuibao tablet.The clinical efficacy,TCM syndrome score,24 h urine volume,serum creatinine(Scr),microalbumin in urine(mAlb),neutrophil Gelatinase related lipid delivery albumin(NGAL)of the two groups were compared,and the adverse reactions and complications of the two groups were observed.Results:After 14 d of treatment,when the treatment group reached the 10th case,the experimental line contacted the upper bound U-line and reached the experimental standard to terminate the experiment.The effective hypothesis was accepted,and it was believed that the Zhuang medicine Yingbupu decoction had a therapeutic effect on stage I and II AKI.The conclusion was drawn that the treatment group received the Zhuang medicine Yingbupu.The clinical effective rate and improvement days were similar between the two groups,and there was no significant difference(P>0.05).However,the integral value of traditional Chinese medicine syndrome in the treatment group was lower than that in the control group(P<0.05),After treatment,the Scr,mAlb,and NGAL levels of patients in both groups were lower than before treatment(P<0.05).After treatment,the Scr,mAlb,and NGAL values in the treatment group were significantly lower than those in the control group(P<0.05).After treatment,the 24-hour urine volume in both groups was higher than that before treatment,and the values in the treatment group were significantly higher than those in the control group(P<0.05).During the treatment period,there were no significant adverse reactions or complications in either group.Conclusion:The Zhuang medicine Yingbupu decoction is effective in treating stage I and II AKI,and the Zhuang medicine Yingbupu can significantly improve the symptoms and quality of life of patients with stage I and II AKI.Its improvement of renal function is better than that of Jinshuibao tablets,and its safety is good.
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.
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National Natural Science Foundation of China(82360895)Yunnan Provincial Science and Technology Department Basic Research Program of Traditional Chinese Medicine Joint Special[2019FF002(-028)]+2 种基金Key Laboratory of Formulation Granules of Yunnan Province(202105AG070014)National Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project‘Dai Pharmacy’(zyyzdxk-2023192)Graduate Supervisor Team Project of Yunnan University of Chinese Medicine(30970102862).
文摘[Objectives]To systematically analyze the risk factors for acute kidney injury(AKI)in patients treated with antibiotics and to conduct a meta-analysis of published clinical studies.[Methods]PubMed,Web of Science,and Embase were searched for relevant cohort and case-control studies from January 1,2001,to October 31,2022.Meta-analysis was performed using RevMan5.4 and StataMP15.[Results]A total of 22 studies were included.Regarding patient factors,serum creatinine(SCr;MD=1.03,95%CI of-0.07 to-0.02)was associated with increased antibiotic-associated AKI.Regarding the comorbidities and clinical factors,diabetes(OR=1.34,95%CI of 1.06 to 1.69,tumor(OR=2.07,95%CI of 1.13 to 3.79),pneumonia(OR=1.83,95%CI of 1.24 to 2.71),mechanical ventilation(OR=3.44,95%CI of 1.93 to 6.12),and ICU admission(OR=2.83,95%CI of 2.13 to 3.75)increased the risk of AKI in patients receiving antibiotic therapy.Regarding drug factors,diuretics(OR=2.76,95%CI of 2.16 to 3.52)increased the risk of antibiotic-associated AKI.[Conclusions]This paper may assist clinicians in predicting the risk factors for AKI in patients receiving antibiotic therapy.