Objective Heart failure(HF)complicated by acute kidney injury(AKI)significantly impacts patient outcomes,and it is crucial to make early predictions of short-term mortality.This study is focused on developing an interpretable machine learning model to enhance early prediction accuracy in such clinical scenarios.Methods This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ,version 2.0)database.Data from the first 24 hours after admission to the ICU were extracted and divided into a training set(70％)and a validation set(30％).We utilized the SHapley Additive exPlanation(SHAP)method to interpret the workings of an extreme gradient boosting(XGBoost)model and identify key prognostic factors.The XGBoost model's predictive ability was evaluated against three other machine learning models using the area under the curve(AUC)metric,and its interpretation was enhanced using the SHAP method.Results The study included 8 028 patients with HF complicated by AKI.The XGBoost model outperformed the other models,achieving an AUC of 0.93(95％confidence interval[CI]:0.78-0.94;accuracy=0.89),while neural network model showed the worst performance(AUC=0.79,95％CI:0.77-0.82;accuracy=0.82).Decision curve analysis showed the superior net benefit of the XGBoost model within the 9％to 60％threshold probabilities.SHAP analysis was performed to identify the top 20 predictors,with age(mean SHAP value 1.29)and Glasgow Coma Scale score(mean SHAP value 1.24)emerging as significant factors.Conclusions Our interpretable model offers an enhanced ability to predict mortality risk in HF patients with AKI in ICUs.This model can be used to assist in formulating effective treatment plans and optimizing resource allocation.

Objective To design and prepare a high efficiency bilirubin adsorbent with good mechanical properties and biocompatibility.Methods In this study,quaternary ammonium pyridine was designed and synthesized,and then modified polyether sulfone microspheres,or PES/p(4-VP-co-N-VP)@6 microspheres,were prepared by phase conversion and electrostatic spraying.The morphology of the polymer components and the microspheres were studied by means of nuclear magnetic resonance(NMR)spectroscopy and scanning electron microscopy.The basic properties of the microspheres and their bilirubin adsorption efficiency were tested,and the adsorption mechanism was further explored.Blood cell counts and the clotting time of the microspheres were also measured.Results The diameter of the modified polyether sulfone microspheres prepared in the study was approximately 700-800 μm.Compared with the original PES microspheres,the surface and internal structure of PES/p(4-VP-co-N-VP)@6 microspheres did not change significantly,and they also had a loose porous structure,with some micropores scattered around in addition to irregular large pores.Compared with the control group,the bilirubin removal effect of the modified microspheres was(94.91±0.73)%after static adsorption in bilirubin PBS buffer solution for 180 min,with the difference being statistically significant(P＜0.0001).According to the findings for the clotting time,the activated partial thromboplastin time(APTT)of the blank plasma group,the control PES group,and the modified PES microsphere group were(27.57±1.25)s,(28.47±0.45)s,and(30.4±0.872)s,respectively,and the difference between the experimental group and the other two groups was statistically significant(P＜0.01,P＜0.05).There was no significant change in red blood cell and white blood cell counts.Conclusion The microspheres prepared in the study have high efficiency in bilirubin adsorption,excellent mechanical properties and thermal stability,and good blood biocompatibility,and are expected to be used in the clinical treatment of patients with liver failure.

Objective Sepsis-induced acute respiratory distress syndrome(ARDS)is an independent risk factor for mortality in critically ill septic patients.However,effective therapeutic targets are still unavailable due to the lack of understanding of its unclear pathogenesis.With increasing understanding in the roles of circulating histones and endothelial dysfunction in sepsis,we aimed to investigate the mechanism of histone-induced endothelial dysfunction leading to sepsis-induced ARDS and to provide experimental support for histone-targeted treatment of sepsis-induced ARDS.Methods First of all,in vitro experiments were conducted.Human umbilical vein endothelial cells(HUVEC)were stimulated with gradient concentrations of histones to explore for the optimal stimulation concentration in vitro.Then,HUVEC were exposed to histones at an optimal concentration with or without resatorvid(TAK-242),a selective inhibitor of Toll-like receptor 4(TLR4),for 24 hours for modeling.The cells were divided into 4 groups:1)the blank control group,2)the blank control+TAK-242 intervention group,3)the histone stimulation group,and 4)the histone+TAK-242 intervention group.HUVEC apoptosis was determined by flow cytometry,VE-Cadherin expression in endothelial cells was determined by Western blot,and the integrity of adhesion connections between endothelial cells was evaluated with confocal fluorescence microscopic images.Male C57BL/6 mice aged 6-8 weeks and weighing 22-25 g were used for the in vivo experiment.Then,the mice were given cecal ligation and puncture(CLP)as well as histone injection at 50 mg/kg via the tail vein for sepsis modeling.The experimental animals were divided into 6 groups:1)the blank control group,2)the blank control+TAK-242 intervention group,3)the CLP model group,4)the CLP+TAK-242 intervention group,5)the histone model group,and 6)the histone+TAK-242 intervention group.After 24 h,the concentrations of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were determined using ELISA kits.Western blot was performed to determine the expression of vascular endothelial(VE)-cadherin in the lung tissue.Hematoxylin and eosin(HE)staining was performed to observe the pathological changes in the lung tissue of the mice.Evans Blue was injected via the tail vein 30 min before the mice were sacrificed.Lung tissue was collected after the mice were sacrificed.Then,the concentrations of Evans blue dye per unit mass in the lung tissue from mice of different groups were evaluated,the rates of pulmonary endothelial leakage were calculated,and the integrity of the pulmonary endothelial barrier was evaluated.Results The results of the in vitro experiment showed that,compared with those of the control group,HUVEC apoptosis was significantly increased under histone stimulation(P＜0.05),the expression of VE-cadherin was decreased(P＜0.05),and the integrity of adherens junctions between endothelial cells was damaged.TAK-242 can significantly inhibit histone-induced HUVEC apoptosis and VE-cadherin expression reduction and maintain the integrity of adherens junctions between endothelial cells.According to the findings from the in vivo experiments,in mice with CLP-induced and histone-induced sepsis,TAK-242 effectively alleviated the increase in serum concentrations of IL-6 and TNF-α,reduced the downregulation of VE-cadherin expression in the lung tissue(P＜0.05),decreased endothelial permeability of the lung vessels,and improved pathological injury in the lung tissue.Conclusion By binding to TLR-4,histone decreases VE-cadherin expression on the surface of vascular endothelial cells,disrupts the integrity of intercellular adherens junctions,and triggers pathological damage to lung tissue.Using TLR-4 inhibitors can prevent sepsis-induced ARDS in histone-induced sepsis.

Uremic pruritus,a severe complication in patients with chronic kidney disease,is associated with a high prevalence.It can cause depression and sleep disorders,and seriously affect the quality of life and the social relations of patients.Recently,there is growing evidence showing that κ-opioid receptor agonists,including nalfurafine,difelikefalin,and nalbuphine,can effectively and safely reduce itching symptoms in patients with refractory uremic pruritus.Herein,we reviewed the epidemiology,pathogenesis,clinical symptoms,and treatment strategies of uremic pruritus,and summarized in detail the progress in clinical research on the use of κ-opioid receptor agonists,including nalfurafine,difelikefalin,and nalbuphine,in the management of patients with uremic pruritus.

Diabetic kidney disease (DKD) is a type of chronic kidney disease (CKD) caused by diabetes. The clinical diagnosis of DKD is usually based on the presence of increased albuminuria and/or decreased estimated glomerular filtration rate (eGFR), and exclusion of other causes of CKD. The clinical features of DKD are proteinuria, gradual decline in renal function, and severe renal failure in the later stages, which is one of the main causes of death in patients with diabetes. Any single biomarker might be insufficient to evaluate renal injury; thus, multiple methods and markers are needed. In addition, diabetic patients should be paid more attention to the kidney, and kidney damage should be evaluated with standardized assessment aimed at strengthening the early prediction and diagnosis of DKD.

Acute kidney injury (AKI) is a serious clinical problem with high morbidity and mortality. Renal replacement therapy (RRT) is an important tool for treating patients with AKI. The 2011 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI points out that RRT should be discontinued when renal function has recovered enough to meet the body needs or when RRT is no longer consistent with treatment goals. However, the specific reference index of weaning RRT is unclear. The guiding roles of traditional indicators such as urine output (> 400 mL/24 h), serum creatinine (SCr, decreasing trend), creatinine clearance (CCr, > 20 mL/min), and novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), hepatocyte growth factor (HGF), interleukins (IL-6, IL-10), kidney injury molecule-1 (KIM-1), kynurenic acid, etc. for discontinuation of RRT in AKI patients were reviewed. Particularly, the importance of biomarkers for this purpose was highlighted.

On May 12,2008,a disastrous earthquake scaled 8.0 Richter hit Wenchuan,Sichuan province in China.Treating the acute kidney injury caused by crush syndrome in survivals of the earthquake has been a big challenge to the nephrologists.In this paper,we shared our experiences on the multi-disciplinary collaboration in management of acute kidney injury caused by crush syndrome.In addition to surgical therapy for crush injury and compartment syndrome and the renal replacement therapy for acute renal injury and its related complications,the early multi-disciplinary collaboration including rehabilitation,mental health care,infection control and ICU also contributed greatly to the successful treatment of the victims of the earthquake.

Objective To explore the effects of intra-jugular vein dual lumen catheter lock heparin in different concentrations on the coagulation function,hemorrhagic tendency and catheter thrombosis risk in hemodialysis patients,and to investigate the reasonable lock heparin cuncentration. Method Ninety end stage renal disease (ESRD)patients receiving regular hemodialysis were enrolled and randomly assigned into 3 groups(n=30):Group A(pure heparin lock solution,6250 U/m1),GrouP B(medium heparin lock solution,1040 U/ml)and Group C(low hepafin lock solution,625 U/ml).The coagulation indexes were determined in short term.Complications such as bleeding,thrombosis,infection and thrombocytopenia were monitored.Results Prothrombin time(PT),actiwtted partial thromboplastin time(APTT)and thrombin time (TT)were significantly prolonged in Group A(P＜0.01);only APTT was signifieanlly prolonged in Group B:however,no significant changes were observed in Group C.Hemorrhage risk was much higher in Group A than that in Group B and C (26.7%vs 10%and 0.P＜0.05).Catheter thrombosis incidence was significantly higher in Group C than that in Group A and B(23.3%vs 0and 10%,P＜0.05).Only 1 suspected catheter related infection was found in Group C,and 2cases of moderated thrombocytopenia in Group A. Concltrsion Moderate concentration of lock heparin solution has the best balance of hemorrhagic and thrombotic risk,and should be recommended to most of regular hemodialysis patients.

0.05).Conclusion Peritoneal dialysis may lead to lower inflammatory and oxidative stress state than the non-dialysis uremic.HPD patients may be in higher oxidative stress and inflammatory state than LPD patients.

Objective To evaluate the effects of Radix Astr agali combined with prednisone and i mmunosuppressant for primary nephrotic syndrome (PNS)in adults and to compare the effects o f Radix Astragali in various prepata tions for PNS.Methods Randomized controlled trials were a pplied for systemic reviews.Electr onic and manual retrieve of Medline,Embase,Cochrane Library,CBMdisc a nd CEBM/CCD and relevant medical jou rnals in China were applied to search the RCTs of Radix Astragali,non -specific treatment,glucocorticoids and i mmunosuppresants for PNS,and the RCTs were analysed with RevMan 4.1.Results There were 14randomized controlled trials with 524cases involved.Meta-analysis showed that Radix Astragali could in crease the therapeutic effect of pre dnisone and immunosuppressant for PNS and re-duce its recurrence.Radix Astragali also had an effect in decreasing 24-hour proteinuria content and the pla sma levels of total cholesterol and albumin.There were no differences between single injection and compound decoction.Asymmetry showed in"Funnel plot"may be related to publication bias,l ow quality of methodology and small -size in sample.Conclusion Radix Astragali and its prescriptio n may become a prospect therapy for PN S and its recurrence and the com-bination of traditional Chinese med icine and western medicine can be more effective for PNS.The dedinite effect of Radix Astragali for PNS will be further con firmed by multiple -center,large -s ample randomized controlled trial.