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.

Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block:A systematic review and meta-analysis

BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Three-dimensional limit variation analysis on the ultimate pullout capacity of the anchor cables based on the Hoek-Brown failure criterion

Only simplified two-dimensional model and a single failure mode are adopted to calculate the ultimate pullout capacity(UPC)of anchor cables in most previous research.This study focuses on a more comprehensive combination failure mode that consists of bond failure of an anchorage body and failure of an anchored rock mass.The three-dimensional ultimate pullout capacity of the anchor cables is calculated based on the Hoek-Brown failure criterion and variation analysis method.The numerical solution for the curvilinear function in fracture plane is obtained based on the finite difference theory,which more accurately reflects the failure state of the anchor cable,as opposed to that being assumed in advance.The results reveal that relying solely on a single failure mode for UPC calculations has limitations,as changes in parameter values not only directly impact the UPC value but also can alter the failure model and thus the calculation method.

Failure mechanism and infrared radiation characteristic of hard siltstone induced by stratification effect

The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and temporal damage mechanism of hard siltstone. The uniaxial compression tests, coupled with acoustic emission(AE) and infrared radiation temperature(IRT) were conducted on siltstones with different stratification effects. The results revealed that the stratigraphic structure significantly affects the stress-strain response and strength degradation characteristics. The mechanical parameters exhibit anisotropy characteristics, and the stratification effect exhibits a negative correlation with the cracking stress and peak stress. The failure modes caused by the stratification effect show remarkable anisotropic features, including splitting failure(Ⅰ: 0°-22.50°, Ⅱ: 90°), composite failure(45°), and shearing failure(67.50°). The AE temporal sequences demonstrate a stepwise response characteristic to the loading stress level. The AE intensity indicates that the stress sensitivity of shearing failure and composite failure is generally greater than that of splitting failure. The IRT field has spatiotemporal migration and progressive dissimilation with stress loading and its dissimilation degree increases under higher stress levels. The stronger the stratification effect, the greater the dissimilation degree of the IRT field. The abnormal characteristic points of average infrared radiation temperature(AIRT) variance at local stress drop and peak stress can be used as early and late precursors to identify fracture instability. Theoretical analysis shows that the competitive relationship between compaction strengthening and fracturing damage intensifies the dissimilation of the infrared thermal field for an increasing stress level. The present study provides a theoretical reference for disaster warnings in hard sedimentary rock mass.

Local failure mechanism of sand-blocking fence in latticed dune along desert roads

The latticed dunes in the Tengger Desert are widely distributed,and the sand-blocking fence placed here are highly susceptible to local failure due to complex wind-sand activities,posing a serious threat to the safe operation of the highway.To explore the local failure mechanism of sand-blocking fence in the latticed dune area,the local failure of sand-blocking fence in the latticed dune areas along the Wuhai-Maqin Highway in China was observed.Taking the first main ridge of the latticed dune as the placement location,the structure of the wind-sand flow field of sand-blocking fence placed at top,the bottom and the middle of windward slope was analyzed by Computational Fluid Dynamics(CFD).The results show that when placed at top of the first main ridge,the wind speed near the sand-blocking fence is the highest,up to 15.23 m/s.Therefore,the wind load strength on the sand barrier is correspondingly larger,up to 232.61 N∙m-2.As the strength of material continues to decrease,the nylon net is prone to breakage.The roots of the angle steel posts are susceptible to hollowing by vortex action,which can cause sand-blocking fence to fall over in strong wind conditions.When placed at the bottom of windward slope,wind speed drop near sand-blocking fence is greatest,with the decrease of 12.48-14.32 m/s compared to the original wind speed.This is highly likely to lead to large-scale deposition of sand particles and burial of the sand-blocking fence.When placed in the middle of windward slope,sand-blocking fence is subjected to less wind load strength(168.61N∙m-2)and sand particles are mostly deposited at the bottom of windward slope,with only a small amount of sand accumulating at the root of sand-blocking fence.Based on field observations and numerical modelling results,when the sand-blocking fence is placed in latticed dune area,it should be placed in the middle of the windward slope of the first main ridge as a matter of priority.Besides the sand-blocking fence should be placed at the top of the first main ridge,and sand fixing measures should be added.

Stability analysis of intermittently jointed rock slopes based on the stepped failure mode

In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermittently bedding jointed rock slopes,the correlation and difference in strength parameters between joints and rock bridges,along with the various failure modes and intermittency of rock bridges,contribute to the complexity of stepped failure modes and the unpredictability of failure regions.Based on the upper-bound limit analysis method and multi-sliders step-path failure mode,considering the shear and tensile failure of rock bridges and the weakened relationship between the strength parameters of rock bridges and jointed surfaces,by introducing the modified M-C failure criterion and the formula for calculating the energy consumption of tensile failure of rock bridges,two failure mechanisms are constructed to obtain the safety factor(F_(s))of intermittently jointed rock slopes.The sequential quadratic programming method is used to obtain the optimal upper-bound solution for F_(s).The influence of multiple key parameters(slope height H,horizontal distance L,Slope angleβ,shear strength parameters of the rock bridgeφr and cr,Dimensionless parameter u,weakening coefficients of the internal friction angle and cohesion between the rock bridges and joint surfaces Kφand Kc)on the stability analysis of intermittently jointed rock slopes under the shear failure mode of rock bridges as well as under the tensile failure mode is also explored.The reliability of the failure mechanisms is verified by comparative analysis with theoretical results,numerical results,and landslide cases,and the variation rules of F_(s)with each key parameter are obtained.The results show that F_(s) varies linearly withφr and cr of the rock bridge and with K_(φ)and K_(c),whereas F_(s)changes nonlinearly with H and L.In particular,with the increase in Kφand Kc,Fs increases by approximately 52.78%and 171.02%on average,respectively.For rock bridge tensile failure,F_(s) shows a nonlinearly positive correlation withφr,cr,Kφand Kc.In particular,with the increase in Kφand Kc,Fs increases by approximately 13%and 61.69%on average,respectively.Fs decreases rapidly with increasing slope gradientβand decreasing dimensionless parameterμ.When Kφand Kc are both less than 1.0,the stepped sliding surface occurs more easily than the plane failure surface,especially in the case of tensile failure of the rock bridge.In addition,rock slopes with higher strength parameters,taller heights,and greater weakening coefficients are prone to rock bridge tension failure with lower Fs,and more attention should be given to the occurrence of such accidents in actual engineering.

Roughness characterization and shearing dislocation failure for rock-backfill interface

Shearing dislocation is a common failure type for rock–backfill interfaces because of backfill sedimentation and rock strata movement in backfill mining goaf.This paper designed a test method for rock–backfill shearing dislocation.Using digital image techno-logy and three-dimensional(3D)laser morphology scanning techniques,a set of 3D models with rough joint surfaces was established.Further,the mechanical behavior of rock–backfill shearing dislocation was investigated using a direct shear test.The effects of interface roughness on the shear–displacement curve and failure characteristics of rock–backfill specimens were considered.The 3D fractal dimen-sion,profile line joint roughness coefficient(JRC),profile line two-dimensional fractal dimension,and the surface curvature of the frac-tures were obtained.The correlation characterization of surface roughness was then analyzed,and the shear strength could be measured and calculated using JRC.The results showed the following:there were three failure threshold value points in rock–backfill shearing dis-location:30%–50%displacement before the peak,70%–90%displacement before the peak,and 100%displacement before the peak to post-peak,which could be a sign for rock–backfill shearing dislocation failure.The surface JRC could be used to judge the rock–backfill shearing dislocation failure,including post-peak sliding,uniform variations,and gradient change,corresponding to rock–backfill disloca-tion failure on the field site.The research reveals the damage mechanism for rock–backfill complexes based on the free joint surface,fills the gap of existing shearing theoretical systems for isomerism complexes,and provides a theoretical basis for the prevention and control of possible disasters in backfill mining.

Pressure stimulated current in progressive failure process of combined coal-rock under uniaxial compression:Response and mechanism

Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.

Energy evolution and structural health monitoring of coal under different failure modes:An experimental study

Structural instability in underground engineering,especially in coal-rock structures,poses significant safety risks.Thus,the development of an accurate monitoring method for the health of coal-rock bodies is crucial.The focus of this work is on understanding energy evolution patterns in coal-rock bodies under complex conditions by using shear,splitting,and uniaxial compression tests.We examine the changes in energy parameters during various loading stages and the effects of various failure modes,resulting in an innovative energy dissipation-based health evaluation technique for coal.Key results show that coal bodies go through transitions between strain hardening and softening mechanisms during loading,indicated by fluctuations in elastic energy and dissipation energy density.For tensile failure,the energy profile of coal shows a pattern of “high dissipation and low accumulation” before peak stress.On the other hand,shear failure is described by “high accumulation and low dissipation” in energy trends.Different failure modes correlate with an accelerated increase in the dissipation energy before destabilization,and a significant positive correlation is present between the energy dissipation rate and the stress state of the coal samples.A novel mathematical and statistical approach is developed,establishing a dissipation energy anomaly index,W,which categorizes the structural health of coal into different danger levels.This method provides a quantitative standard for early warning systems and is adaptable for monitoring structural health in complex underground engineering environments,contributing to the development of structural health monitoring technology.

A Comparative Study on the Post-Buckling Behavior of Reinforced Thermoplastic Pipes(RTPs)Under External Pressure Considering Progressive Failure

The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical simulations,the eigenvalue analysis and Riks analysis are combined,in which the Hashin failure criterion and fracture energy stiffness degradation model are used to simulate the progressive failure of composites,and the“infinite”boundary conditions are applied to eliminate the boundary effects.As for the hydrostatic pressure tests,RTP specimens were placed in a hydrostatic chamber after filled with water.It has been observed that the cross-section of the middle part collapses when it reaches the maximum pressure.The collapse pressure obtained from the numerical simulations agrees well with that in the experiment.Meanwhile,the applicability of NASA SP-8007 formula on the collapse pressure prediction was also discussed.It has a relatively greater difference because of the ignorance of the progressive failure of composites.For the parametric study,it is found that RTPs have much higher first-ply-failure pressure when the winding angles are between 50°and 70°.Besides,the effect of debonding and initial ovality,and the contribution of the liner and coating are also discussed.

Finite Element Simulations on Failure Behaviors of Granular Materials with Microstructures Using a Micromechanics-Based Cosserat Elastoplastic Model

This paper presents a micromechanics-based Cosserat continuum model for microstructured granular materials.By utilizing this model,the macroscopic constitutive parameters of granular materials with different microstructures are expressed as sums of microstructural information.The microstructures under consideration can be classified into three categories:a medium-dense microstructure,a dense microstructure consisting of one-sized particles,and a dense microstructure consisting of two-sized particles.Subsequently,the Cosserat elastoplastic model,along with its finite element formulation,is derived using the extended Drucker-Prager yield criteria.To investigate failure behaviors,numerical simulations of granular materials with different microstructures are conducted using the ABAQUS User Element(UEL)interface.It demonstrates the capacity of the proposed model to simulate the phenomena of strain-softening and strain localization.The study investigates the influence of microscopic parameters,including contact stiffness parameters and characteristic length,on the failure behaviors of granularmaterials withmicrostructures.Additionally,the study examines themesh independence of the presented model and establishes its relationship with the characteristic length.A comparison is made between finite element simulations and discrete element simulations for a medium-dense microstructure,revealing a good agreement in results during the elastic stage.Somemacroscopic parameters describing plasticity are shown to be partially related to microscopic factors such as confining pressure and size of the representative volume element.

Dynamic response and failure process of horizontal-layered fractured structure rock slope under strong earthquake

Rock slope with horizontal-layered fractured structure(HLFS)has high stability in its natural state.However,a strong earthquake can induce rock fissure expansion,ultimately leading to slope failure.In this study,the dynamic response,failure mode,and spectral characteristics of rock slope with HLFS under strong earthquake conditions were investigated based on the large-scale shaking table model test.On this basis,multiple sets of numerical calculation models were further established by UDEC discrete element program.Five influencing factors were considered in the parametric study of numerical simulations,including slope height,slope angle,bedding-plane spacing and secondary joint spacing as well as bedrock dip angle.The results showed that the failure process of rock slope with HLFS under earthquake action is mainly divided into four phases,i.e.,the tensile crack of the slope shoulder joints and shear dislocation at the top bedding plane,the extension of vertical joint cracks and increase of shear displacement,the formation of step-through sliding surfaces and the instability,and finally collapse of fractured rock mass.The acceleration response of slopes exhibits elevation amplification effect and surface effect.Numerical simulations indicate that the seismic stability of slopes with HLFS exhibits a negative correlation with slope height and angle,but a positive correlation with bedding-plane spacing,joint spacing,and bedrock dip angle.The results of this study can provide a reference for seismic stability evaluation of weathered rock slopes.

Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit

BACKGROUND Cirrhotic patients with acute-on-chronic liver failure(ACLF)in the intensive care unit(ICU)have a poor but variable prognoses.Accurate prognosis evaluation can guide the rational management of patients with ACLF.However,existing prognostic scores for ACLF in the ICU environment lack sufficient accuracy.AIM To develop a new prognostic model for patients with ACLF in ICU.METHODS Data from 938 ACLF patients in the Medical Information Mart for Intensive Care(MIMIC)database were used to develop a new prognostic model(MIMIC ACLF)for ACLF.Discrimination,calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve(AUROC),calibration curve and decision curve analysis(DCA),respectively.MIMIC ACLF was then externally validated in a multiple-center cohort,the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in China.RESULTS The MIMIC ACLF score was determined using nine variables:ln(age)×2.2+ln(white blood cell count)×0.22-ln(mean arterial pressure)×2.7+respiratory failure×0.6+renal failure×0.51+cerebral failure×0.31+ln(total bilirubin)×0.44+ln(internationalized normal ratio)×0.59+ln(serum potassium)×0.59.In MIMIC cohort,the AUROC(0.81/0.79)for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF(0.76/0.74),Model for End-stage Liver Disease(MELD;0.73/0.71)and MELD-Na(0.72/0.70)(all P<0.001).The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing scores.The net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50%threshold probability.The superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external cohorts.CONCLUSION We developed and validated a new prognostic model with satisfactory accuracy for cirrhotic patients with ACLF hospitalized in the ICU.The model-based risk stratification and online calculator might facilitate the rational management of patients with ACLF.

Evolution model and failure mechanisms of rainfall-induced cracked red clay slopes:insights from Xinshao County,China

Red clay landslides are widely distributed worldwide,resulting in severe loss of life and property.Although rainfall-induced red clay slopes have received extensive attention,the role of cracks in the evolutionary process of red clay slopes and their connection to failure mechanisms is still poorly understood.A comprehensive approach integrating field investigation,laboratory tests,and numerical simulations was conducted to study the 168 red clay landslides in Xinshao County,China.The results show that red clay is prone to forming cracks at high moisture content due to its low swelling and high shrinkage properties.The failure mode of red clay slopes can be summarized in three stages:crack generation,slope excavation,and slope failure.Furthermore,the retrospective analysis and numerical simulations of the typical landslide in Guanchong indicated that intense rainfall primarily impacts the shallow layer of soil within approximately 0.5 m on the intact slope.However,cracks change the pattern of rainfall infiltration in the slope.Rainwater infiltrates rapidly through the preferential channels induced by the cracks rather than uniformly and slowly from the slope surface.This results in a significant increase in both the depth of infiltration and the saturated zone area of the cracked slope,reaching 3.8 m and 36.2 m^(2),respectively.Consequently,the factor of safety of the slope decreases by 13.4%compared to the intact slope,ultimately triggering landslides.This study can provide valuable insights into understanding the failure mechanisms of red clay slopes in China and other regions with similar geological settings.

Disturbance failure mechanism of highly stressed rock in deep excavation:Current status and prospects

This article reviews the current status on the dynamic behavior of highly stressed rocks under disturbances.Firstly,the experimental apparatus,methods,and theories related to the disturbance dynamics of deep,high-stress rock are reviewed,followed by the introduction of scholars’research on deep rock deformation and failure from an energy perspective.Subsequently,with a backdrop of highstress phenomena in deep hard rock,such as rock bursts and core disking,we delve into the current state of research on rock microstructure analysis and residual stresses from the perspective of studying the energy storage mechanisms in rocks.Thereafter,the current state of research on the mechanical response and the energy dissipation of highly stressed rock formations is briefly retrospected.Finally,the insufficient aspects in the current research on the disturbance and failure mechanisms in deep,highly stressed rock formations are summarized,and prospects for future research are provided.This work provides new avenues for the research on the mechanical response and damage-fracture mechanisms of rocks under high-stress conditions.

Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-onchronic liver failure

BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

Numerical investigation of hydro-morphodynamic characteristics of a cascading failure of landslide dams

A cascading failure of landslide dams caused by strong earthquakes or torrential rains in mountainous river valleys can pose great threats to people’s lives,properties,and infrastructures.In this study,based on the three-dimensional Reynoldsaveraged Navier-Stokes equations(RANS),the renormalization group(RNG)k-εturbulence model,suspended and bed load transport equations,and the instability discriminant formula of dam breach side slope,and the explicit finite volume method(FVM),a detailed numerical simulation model for calculating the hydro-morphodynamic characteristics of cascading dam breach process has been developed.The developed numerical model can simulate the breach hydrograph and the dam breach morphology evolution during the cascading failure process of landslide dams.A model test of the breaches of two cascading landslide dams has been used as the validation case.The comparison of the calculated and measured results indicates that the breach hydrograph and the breach morphology evolution process of the upstream and downstream dams are generally consistent with each other,and the relative errors of the key breaching parameters,i.e.,the peak breach flow and the time to peak of each dam,are less than±5%.Further,the comparison of the breach hydrographs of the upstream and downstream dams shows that there is an amplification effect of the breach flood on the cascading landslide dam failures.Three key parameters,i.e.,the distance between the upstream and the downstream dams,the river channel slope,and the downstream dam height,have been used to study the flood amplification effect.The parameter sensitivity analyses show that the peak breach flow at the downstream dam decreases with increasing distance between the upstream and the downstream dams,and the downstream dam height.Further,the peak breach flow at the downstream dam first increases and then decreases with steepening of the river channel slope.When the flood caused by the upstream dam failure flows to the downstream dam,it can produce a surge wave that overtops and erodes the dam crest,resulting in a lowering of the dam crest elevation.This has an impact on the failure occurrence time and the peak breach flow of the downstream dam.The influence of the surge wave on the downstream dam failure process is related to the volume of water that overtops the dam crest and the erosion characteristics of dam material.Moreover,the cascading failure case of the Xiaogangjian and Lower Xiaogangjian landslide dams has also been used as the representative case for validating the model.In comparisons of the calculated and measured breach hydrographs and final breach morphologies,the relative errors of the key dam breaching parameters are all within±10%,which verify the rationality of the model is applicable to real-world cases.Overall,the numerical model developed in this study can provide important technical support for the risk assessment and emergency treatment of failures of cascading landslide dams.

Failure to Rescue as a Quality Metric in Congenital Heart Surgeries in a High-Complexity Service Provider Institution Located in a Middle-Income Country

Background:Failure to rescue has been an effective quality metric in congenital heart surgery.Conversely,mor-bidity and mortality depend greatly on non-modifiable individual factors and have a weak correlation with better-quality performance.We aim to measure the complications,mortality,and risk factors in pediatric patients undergoing congenital heart surgery in a high-complexity institution located in a middle-income country and compare it with other institutions that have conducted a similar study.Methods:A retrospective observational study was conducted in a high-complexity service provider institution,in Cali,Colombia.All pediatric patients undergoing any congenital heart surgery between 2019 and 2022 were included.The main outcomes evaluated in the study were complication,mortality,and failure to rescue rate.Univariate and multivariate logistic regression analysis was performed with mortality as the outcome variable.Results:We evaluated 308 congenital heart sur-geries.Regarding the outcomes,201(65%)complications occurred,23(7.5%)patients died,and the FTR of the entire cohort was 11.4%.The presence of a postoperative complication(OR 14.88,CI 3.06–268.37,p=0.009),age(OR 0.79,CI 0.57–0.96,p=0.068),and urgent/emergent surgery(OR 8.14,CI 2.97–28.66,p<0.001)were the most significant variables in predicting mortality.Conclusions:Failure to rescue is an effective and comparable quality measure in healthcare institutions and is the major contributor to postoperative mortality in congenital heart surgeries.Despite our higher mortality and complication rate,we obtained a comparable failure to rescue rate to high-income countries’health institutions.

Numerical three-dimensional modeling of earthen dam piping failure

A physically-based numerical three-dimensional earthen dam piping failure model is developed for homogeneous and zoned soil dams.This model is an erosion model,coupled with force/moment equilibrium analyses.Orifice flow and two-dimensional(2D)shallow water equations(SWE)are solved to simulate dam break flows at different breaching stages.Erosion rates of different soils with different construction compaction efforts are calculated using corresponding erosion formulae.The dam's real shape,soil properties,and surrounding area are programmed.Large outer 2D-SWE grids are used to control upstream and downstream hydraulic conditions and control the boundary conditions of orifice flow,and inner 2D-SWE flow is used to scour soil and perform force/moment equilibrium analyses.This model is validated using the European Commission IMPACT(Investigation of Extreme Flood Processes and Uncertainty)Test#5 in Norway,Teton Dam failure in Idaho,USA,and Quail Creek Dike failure in Utah,USA.All calculated peak outflows are within 10%errors of observed values.Simulation results show that,for a V-shaped dam like Teton Dam,a piping breach location at the abutment tends to result in a smaller peak breach outflow than the piping breach location at the dam's center;and if Teton Dam had broken from its center for internal erosion,a peak outflow of 117851 m'/s,which is 81%larger than the peak outflow of 65120 m3/s released from its right abutment,would have been released from Teton Dam.A lower piping inlet elevation tends to cause a faster/earlier piping breach than a higher piping inlet elevation.