Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system

BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

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.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

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.

Acute liver failure:A clinically severe syndrome characterized by intricate mechanisms

Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates.Its underlying mechanisms are intricate,involving intricate interplays between various cells.Given the current scarcity of treatment options,there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes

BACKGROUND Coronary heart disease and type 2 diabetes mellitus(T2DM)frequently coexist,creating a complex and challenging clinical scenario,particularly when complicated with acute myocardial infarction(AMI).AIM To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion.METHODS In total,98 patients were categorized into control(n=47)and observation(n=51)groups.The control group received noxital,while the observation group was treated with dapagliflozin combined with noxital for 6 months.Changes in myocardial microperfusion,blood glucose level,cardiac function,N-terminal prohormone of brain natriuretic peptide(NT-proBNP)level,growth differentiation factor-15(GDF-15)level,and other related factors were compared between the two groups.Additionally,the incidence of major adverse cardiovascular events(MACE)and adverse reactions were calculated.RESULTS After treatment,in the observation and control groups,the corrected thrombolysis in myocardial infarction frame counts were 37.12±5.02 and 48.23±4.66,respectively.The NT-proBNP levels were 1502.65±255.87 and 2015.23±286.31 pg/mL,the N-terminal pro-atrial natriuretic peptide(NT-proANP)levels were 1415.69±213.05 and 1875.52±241.02 ng/mL,the GDF-15 levels were 0.87±0.43 and 1.21±0.56 g/L,and the high-sensitivity C-reactive protein(hs-CRP)levels were 6.54±1.56 and 8.77±1.94 mg/L,respectively,with statistically significant differences(P<0.05).The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group(P<0.05).The incidence of adverse reactions was 13.73%(7/51)in the observation group and 10.64%(5/47)in the control group,with no statistically significant difference(P>0.05).CONCLUSION Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM.The underlying mechanism may be related to the reduction in the expression levels of NT-proANP,GDF-15,and hs-CRP.

Construction of a predictive model for acute liver failure after hepatectomy based on neutrophil-to-lymphocyte ratio and albuminbilirubin score

BACKGROUND Acute liver failure(ALF)is a common cause of postoperative death in patients with hepatocellular carcinoma(HCC)and is a serious threat to patient safety.The neutrophil-to-lymphocyte ratio(NLR)is a common inflammatory indicator that is associated with the prognosis of various diseases,and the albumin-bilirubin score(ALBI)is used to evaluate liver function in liver cancer patients.Therefore,this study aimed to construct a predictive model for postoperative ALF in HCC tumor integrity resection(R0)based on the NLR and ALBI,providing a basis for clinicians to choose appropriate treatment plans.AIM To construct an ALF prediction model after R0 surgery for HCC based on NLR and ALBI.METHODS In total,194 patients with HCC who visited The First People’s Hospital of Lianyungang to receive R0 between May 2018 and May 2023 were enrolled and divided into the ALF and non-ALF groups.We compared differences in the NLR and ALBI between the two groups.The risk factors of ALF after R0 surgery for HCC were screened in the univariate analysis.Independent risk factors were analyzed by multifactorial logistic regression.We then constructed a prediction model of ALF after R0 surgery for HCC.A receiver operating characteristic curve,calibration curve,and decision curve analysis(DCA)were used to evaluate the value of the prediction model.RESULTS Among 194 patients with HCC who met the standard inclusion criteria,46 cases of ALF occurred after R0(23.71%).There were significant differences in the NLR and ALBI between the two groups(P<0.05).The univariate analysis showed that alpha-fetoprotein(AFP)and blood loss volume(BLV)were significantly higher in the ALF group compared with the non-ALF group(P<0.05).The multifactorial analysis showed that NLR,ALBI,AFP,and BLV were independent risk factors for ALF after R0 surgery in HCC.The predictive efficacy of NLR,ALBI,AFP,and BLV in predicting the occurrence of ALT after R0 surgery for HCC was average[area under the curve(AUC)NLR=0.767,AUCALBI=0.755,AUCAFP=0.599,AUCBLV=0.718].The prediction model for ALF after R0 surgery for HCC based on NLR and ALBI had a better predictive efficacy(AUC=0.916).The calibration curve and actual curve were in good agreement.DCA showed a high net gain and that the model was safer compared to the curve in the extreme case over a wide range of thresholds.CONCLUSION The prediction model based on NLR and ALBI can effectively predict the risk of developing ALF after HCC R0 surgery,providing a basis for clinical prevention of developing ALF after HCC R0 surgery.

Clinical study of neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases.We categorize acute pancreatitis by etiology into acute biliary pancreatitis(ABP)and hypertriglyceridemia-induced acute pancreatitis(HTGP).AIM To investigate the clinical significance of NLR and PLR in assessing persistent organ failure(POF)in HTGP and ABP.METHODS A total of 1450 patients diagnosed with acute pancreatitis(AP)for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled.The patients were categorized into two groups according to the etiology of AP:ABP in 530 patients and HTGP in 241 patients.We collected and compared the clinical data of the patients,including NLR,PLR,and AP prognostic scoring systems,within 48 h of hospital admission.RESULTS The NLR(9.1 vs 6.9,P<0.001)and PLR(203.1 vs 160.5,P<0.001)were significantly higher in the ABP group than in the HTGP group.In the HTGP group,both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score≥3.Likewise,in the ABP group,NLR and PLR were significantly elevated in patients with severe AP,modified computed tomography severity index score≥4,Japanese Severity Score≥3,and modified Marshall score≥2.Moreover,NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups.CONCLUSION NLR and PLR vary between ABP and HTGP,are strongly associated with AP prognostic scoring systems,and have predictive potential for the occurrence of POF in both ABP and HTGP.

Revaccination after Acute Kidney Injury Associated with Prior COVID-19 Vaccination: Case Report

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.

Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

Study of the OPG/RANKL/RANK signaling pathway in mice treated with sepsis-related acute kidney injury

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.

Causes and Prognosis of Cases of Acute Obstructive Renal Failure Managed at the Donka National Hemodialysis Center

Introduction: Acute obstructive renal failure (AORF) is a frequent clinical situation, secondary to obstruction of the urinary excretory tract. Whatever the cause, urinary tract obstruction suddenly opposes glomerular filtration and is responsible for tubulointerstitial lesions. It accounts for 10% of acute renal failure (ARF). The aim of this study was to identify the causes and prognosis of cases of acute obstructive renal failure managed at the Centre National d’hémodialyse Donka. Material and Methods: This was a prospective descriptive study lasting 6 months, from September 1, 2022 to February 29, 2023. All patients undergoing haemodialysis for acute obstructive renal failure who agreed to participate in the study and whose medical records were complete were included. Results: During the course of the study, we registered 97 haemodialysis patients, including 20 cases (20.62%) of acute obstructive renal failure. The mean age of the patients was 57.8 ± 10.54 years, with a male predominance of 11 cases (55%) and a sex ratio of 1.22. The reasons for consultation were dominated by physical asthenia 11 cases (55%), lumbar pain 9 cases (50%), vomiting 6 cases (30%) and acute urine retention 6 cases (30%). Arterial hypertension 16 cases (80%) and urinary tract infection 10 cases (50%) were the most common antecedents. The etiologies of RAOI were dominated by lithiasis 10 cases (50%), neoplasia 6 cases (30%) and benign prostatic hypertrophy 3 cases (15%). mean creatinine was 1267.60 ± 710.76 μmol/l with extremes of 243 μmol/l and 2822 μmol/l, mean urea was 39.56 ± 18.36, hyperkalemia in 14 cases (70%) and hyponatremia in 8 cases (40%). After hemodialysis, 9 cases (45%) recovered renal function, 4 cases (20%) became chronic and 7 cases (35%) died. Conclusion: The frequency of AKI remains non-negligible in our department, and early detection and prompt management would considerably reduce the morbidity and mortality associated with this pathology.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Navigating nephrotoxic waters:A comprehensive overview of contrast-induced acute kidney injury prevention

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.

Sequential experimental observation on the curative effect of Yingbupu decoction of Zhuang medicine on stage I and II acute kidney injury

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.

Understanding the molecular crossroads in acute liver failure:A pathway to new therapies

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Risk Factors for Acute Kidney Injury in Patients Receiving Antibiotic Therapy:A Systematic Review and Meta-Analysis

[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.

Pylephlebitis-induced acute liver failure: A case report and review of literature

BACKGROUND Pylephlebitis is an extremely rare form of septic thrombophlebitis involving the portal vein,carrying high rates of morbidity and mortality.CASE SUMMARY We present a case of a 42-year-old male with no past medical history who presented with acute onset of abdominal pain and altered mental status with laboratory tests demonstrating new-onset acute liver failure.Pylephlebitis was determined to be the underlying etiology due to subsequent workup revealing polymicrobial gram-negative anaerobic bacteremia and complete thrombosis of the main and left portal veins.To our knowledge,this is the first documented case of acute liver failure as a potential life-threatening complication of pylephlebitis.CONCLUSION Our case highlights the importance of considering pylephlebitis in the broad differential for abdominal pain,especially if there are co-existing risk factors for hypercoagulability.We also demonstrate that fulminant hepatic failure in these patients can potentially be reversible with the immediate initiation of antibiotics and anticoagulation.