BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease de...BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.展开更多
The features of additive manufacturing(AM)have made commercially pure titanium(CP-Ti)an attractive candidate material for biomedical implants.However,achieving high strength and ductility is challenging because of the...The features of additive manufacturing(AM)have made commercially pure titanium(CP-Ti)an attractive candidate material for biomedical implants.However,achieving high strength and ductility is challenging because of the columnar structures and fine martensite formation.This study investigated the effect of carbon nanotubes(CNTs)addition on the microstructure and mechanical properties of grade 1 CP-Ti(Gr-1)during the laser powder bed fusion(L-PBF)process.A minute amount of 0.2%mass fraction(wt%)CNTs addition resulted in a high yield strength of approximately 700 MPa and exceptional ductility of 25.7%.Therein,a portion of the CNTs dissolved in the matrix as solute atoms,contributing to solution strengthening,while others were transformed into Ti C_(x)through an in situ reaction with the Ti matrix.Furthermore,the addition of CNTs resulted in the formation of a larger fraction of equiaxed grains and increased the activity of basal and prismatic slip systems.Hence,Gr-1 with CNTs exhibited significantly increased ductility while maintaining a high strength comparable to that of Gr-1 without CNTs.The insights gained from this study provide a novel approach for designing strong and ductile Ti alloys for AM.展开更多
Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold...Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC_(50))of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal“dead ends”and“safe bets”for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogeneoxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.展开更多
Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thal...Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thaliana,the OSCA family has been identified as mechanically activated ion channels that respond to osmotic stress by allowing calcium ions to enter the cell.This influx increases the cytoplasmic calcium concentration,triggering osmotic stress-induced signal transduction cascades in plants.In this study,we determined the structures of OSCA2.2 and OSCA3.1 via cryoelectron microscopy(cryo-EM).Both proteins form homodimers consisting of 11 transmembrane helices(TM1–11).The ion conduction pathway is formed by TM4–8.Despite belonging to the same family,OSCA2.2 and OSCA3.1 exhibit notable structural variations.Structural analysis revealed that both OSCA2.2 and OSCA3.1 exhibit a closed conformation.We also conducted functional studies on OSCA proteins via electrophysiological experiments and confirmed the role of key amino acids in the process of ion permeation.展开更多
Silver ion(Ag^(+))is a highly toxic metal ion,and its monitoring in water or food resources has become extraordinarily necessary within the scope of human health.In the light of the fact of Ag^(+)-induced folding stru...Silver ion(Ag^(+))is a highly toxic metal ion,and its monitoring in water or food resources has become extraordinarily necessary within the scope of human health.In the light of the fact of Ag^(+)-induced folding structure of specific peptides,an unlabeled and highselectivity Ag^(+)assay is presented by means of intrinsic fluorescence of peptides.Under the quenching effect of gold nanoparticles(AuNPs),characteristic fluorescence of peptides could be considerably reduced by rapid modification.Along with the Ag adding,the fluorescence signals of peptide-AuNPs are largely enhanced by the behavior between peptides and Agt.This is basically involving the formation of 4-coordinated complexes,generating the changes of peptides in structure and fluorescence properties.Under this circumstance,the adverse influence of plenty of interfering ions is suppressed,including the toxic Hg^(2+),Pb^(2+).The results highlight that Ag ions could be selectively recognized as low as 2.4 nmol/L with a linear range of 5 to 800 nmol/L.In comparison with other programs,the given approach declares simplicity,sensitivity,and superior selectivity.Furthermore,the biosensor excels in the practical application in water samples(e.g.,lake,tap and drinking water)owing to its non-interference and on-site rapid determination.展开更多
With the development of education and technology,the construction of research public platforms has emerged as a critical initiative for many universities and top-tier public hospitals.The core and most fundamental fun...With the development of education and technology,the construction of research public platforms has emerged as a critical initiative for many universities and top-tier public hospitals.The core and most fundamental function of a basic public platform is to aggregate large instruments and specific resources,providing open services for instrumental analysis and sample testing.Optimized management and high-quality,efficient services are essential for such platforms.This article elucidates the construction of a research public platform in West China Hospital,focusing on the adoption of hierarchical management and precise services.The core of the hierarchical management lies in building a multi-level service platform composed of routine support platforms,advanced technology platforms,and specially qualification platforms,while establishing a talent hierarchy that differentiates between core and routine positions.This structure is designed to accurately meet the diverse needs of users and enhance resource efficiency.By implementing user access control with differentiated permissions for internal and external users and a dynamic credit-based review system,the laboratory can ensure safe and efficient operations.The four service modes—instrument usage,in-lab experiments,sample testing,and collaborative projects—are precisely aligned with various research scenarios.Proactive engagement with grant-funded projects,customized services for research groups,and a multidimensional training system further strengthen the platform's support for major scientific research tasks.Through systematic management and service innovation,this model achieves efficient integration and sustainable development of platform resources,providing a valuable reference for the construction of public platforms in similar medical institutions.展开更多
A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing po...A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing potential therapeutic targets.Here,we present an analytical strategy for the deep discovery of heterogeneous metabolism and drug response in the heart tissue of rats with HF using airflow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)coupled with bulk RNAsequencing.Spatial metabolomics illustrated pronounced metabolic heterogeneity between the infarct(I),infarct margin(IM),and non-infarct(NI)areas of heart tissue in HF.Integrated transcriptomics showed that increased mRNA expression of ATP citrate lyase disrupted the tricarboxylic acid(TCA)cycle in the NI area.Impairment of the carnitine shuttle system led to a significant accumulation of carnitines,suggesting potential abnormalities in fatty acid(FA)oxidation.Coupling on-tissue chemical derivatization with AFADESI-MSI enabled us to confirm the occurrence of incomplete oxidation of FAs in the NI area.Additionally,we observed a heterogeneous drug response between the anti-HF medications valsartan and Qishen Yiqi Dripping Pills(QDP).Valsartan exhibited a more pronounced effect on metabolic regulation in the I area,whereas QDP exerted stronger regulatory effects on metabolism in the NI area.Utilizing this method,four potential therapeutic targets were identified in HF:CPT1A,PDHB,ACLY,and BCAT2,which were preliminarily validated by western blotting.Overall,integrating spatial metabolomics with transcriptomics facilitates comprehensive analyses that link differential metabolites and genes,enabling a more precise characterization of metabolic changes in heart injury microareas and providing effective methods for elucidating molecular mechanisms and identifying potential therapeutic targets for HF.展开更多
Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sh...Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.展开更多
Being widespread across the globe,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)keeps evolving and generating new variants and continuously poses threat to public health,especially to the population with ...Being widespread across the globe,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)keeps evolving and generating new variants and continuously poses threat to public health,especially to the population with chronic comorbidities.Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019(COVID-19).Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential.Here,in this study,we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus(db/db),and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters.SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters.Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters,and may induce serious complications such as diabetic kidney disease and cardiac lesions.Our findings demonstrated that despite the decreased respiratory pathogenicity,the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters,suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected.This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes.It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.展开更多
Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly di...Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly diagnosed acute coronary syndrome(ACS)patients and detected seven myocardial enzymes and six kidney function biomarkers.Twelve PFASwere also assessedwith ultra-high-performance liquid chromatography-tandem mass spectrometry.Generalized linear model and restricted cubic spline model were applied to single pollutant analysis.Quantile g-computation was used for mixture analysis.Network model was utilized to identify central and bridge nodes of pollutants and phenotypes.In the present study,perfluorohexane sulfonic acid was positively associated with uric acid(UA)(β=0.04,95%confidence interval(CI):0.01,0.07),and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate(β=-0.04,95%CI:-0.07,-0.01)but positively associated with UA(β=0.03,95%CI:0.01,0.06).In mixture analysis,each quantile increase in the PFAS mixture was significantly associated with UA(β=0.08,95%CI:0.04,0.11).Network analysis revealed that perfluorooctanoate,UA,and myoglobin were denoted as bridge nodes,and the first principal component of lactate dehydrogenase and creatine kinase-myocardial band was identified as the node with the highest strength and expected influence.This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network,which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.展开更多
Widely used spin-coated nickle oxide (NiOx) based perovskite solar cells often suffer from severe interfacial reactions between the NiOxand adjacent perovskite layers due to surface defect states,which inherently impa...Widely used spin-coated nickle oxide (NiOx) based perovskite solar cells often suffer from severe interfacial reactions between the NiOxand adjacent perovskite layers due to surface defect states,which inherently impair device performance in a long-term view,even with surface molecule passivation.In this study,we developed high-quality magnetron-sputtered NiOxthin films through detailed process optimization,and compared systematically sputtered and spin-coated NiOxthin film surfaces from materials to devices.These sputtered NiOxfilms exhibit improved crystallinity,smoother surfaces,and significantly reduced Ni3+or Ni vacancies compared to their spin-coated counterparts.Consequently,the interface between the perovskite and sputtered NiOxfilm shows a substantially reduced density of defect states.Perovskite solar cells (PSCs) fabricated with our optimally sputtered NiOxfilms achieved a high power conversion efficiency (PCE) of up to 19.93%and demonstrated enhanced stability,maintaining 86.2% efficiency during 500 h of maximum power point tracking under one standard sun illumination.Moreover,with the surface modification using (4-(2,7-dibromo-9,9-dimethylacridin-10(9H)-yl)butyl)p hosphonic acid (DMAcPA),the device PCE was further promoted to 23.07%,which is the highest value reported for sputtered NiOxbased PSCs so far.展开更多
Objective:Sheep are commonly used as large animal pre-clinical models for inves-tigating cardiovascular therapies,interventions,anatomy and physiology.Further,novel small diameter vascular grafts are frequently tested...Objective:Sheep are commonly used as large animal pre-clinical models for inves-tigating cardiovascular therapies,interventions,anatomy and physiology.Further,novel small diameter vascular grafts are frequently tested via implantation into sheep carotid arteries(CAs).This is because,unlike humans,acute occlusion of one or both sheep CAs is not associated with morbidity or mortality and thus provides safer experimental testing,with reduced ethical constraints,animal numbers and costs.However,to date there has been no evidence regarding sheep tolerance of femoral artery(FA)occlusion.Methods:In this study,seven sheep underwent CA graft surgery,with digital subtrac-tion angiography(DSA)of the CAs performed every 2 months via femoral access,for a total of 8 months.Four months into the study,the left FA of two sheep became inac-cessible due to a suspected FA occlusion.Thus,femoral angiography was performed,followed by FA dissection,FA histology and retrospective analysis of both veterinar-ian animal monitoring and pain scores.Results:FA angiography and histology confirmed complete left FA occlusion in two sheep.Retrospective animal monitoring demonstrated sheep with occluded FAs did not display increased pain scores or deleterious effects on their gait or wellbeing.Conclusion:Our data shows that sheep tolerate FA occlusion with no symptoms,similar to their cerebral circulation,making them an appropriate model for assessing small diameter femoral graft interposition studies and testing other cardiovascular interventions.展开更多
Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be asso...Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.展开更多
Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elici...Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elicit anti-apoptotic,antiinflammatory and antioxidative responses.Its therapeutic effects have been demonstrated in studies on neurological diseases,peripheral nerve injuries,pain relief and wound healing.We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019.The NCBI PubMed database,EMBASE database,Cochrane Library and ScienceDirect database were searched.We reviewed 95 papers and analyzed.Photobiomodulation has wide applicability in the treatment of stroke,traumatic brain injury,Parkinson’s disease,Alzheimer’s disease,major depressive disorder,and other diseases.Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases.However,additional studies with adequate sample size are needed to optimize treatment parameters.展开更多
AIM To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation.METHODS A total of 1607 consecutive liver transplantations were analyzed in a re...AIM To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation.METHODS A total of 1607 consecutive liver transplantations were analyzed in a retrospective study. Detailed subset analysis was performed in 417 patients, which have been transplanted since the introduction of Model of End-Stage Liver Disease(MELD)-based liver allocation. Risk factors for the onset of anastomotic biliary complications were identified with multivariable binary logisticregression analyses. The identified risk factors in regression analyses were compiled into a prognostic model. The applicability was evaluated with receiver operating characteristic curve analyses. Furthermore, Kaplan-Meier analyses with the log rank test were applied where appropriate. RESULTS Biliary complications were observed in 227 cases(14.1%). Four hundred and seventeen(26%) transplantations were performed after the introduction of MELD-based donor organ allocation. Since then, 21%(n = 89) of the patients suffered from biliary complications, which are further categorized into anastomotic bile leaks [46%(n = 41)], anastomotic strictures [25%(n = 22)], cholangitis [8%(n = 7)] and non-anastomotic strictures [3%(n = 3)]. The remaining 18%(n = 16) were not further classified. After adjustment for all univariably significant variables, the recipient MELD-score at transplantation(P = 0.006; OR = 1.035; 95%CI: 1.010-1.060), the development of hepatic artery thrombosis post-operatively(P = 0.019; OR = 3.543; 95%CI: 1.233-10.178), as well as the donor creatinine prior to explantation(P = 0.010; OR = 1.003; 95%CI: 1.001-1.006) were revealed as independent risk factors for biliary complications. The compilation of these identified risk factors into a prognostic model was shown to have good prognostic abilities in the investigated cohort with an area under the receiver operating curve of 0.702.CONCLUSION The parallel occurrence of high recipient MELD and impaired donor kidney function should be avoided. Risk is especially increased when post-transplant hepatic artery thrombosis occurs.展开更多
As the gap between a shortage of organs and the im-mense demand for liver grafts persists, every available donor liver needs to be optimized for utility, urgency and equity. To overcome this challenge, decision modell...As the gap between a shortage of organs and the im-mense demand for liver grafts persists, every available donor liver needs to be optimized for utility, urgency and equity. To overcome this challenge, decision modelling might allow us to gather evidence from previous studies as well as compare the costs and consequences of alternative options. For public health policy and clinical intervention assessment, it is a potentially powerful tool. The most commonly used types of decision analytical models include decision trees, the Markov model, microsimulation, discrete event simulation and the system dynamic model. Analytic models could support decision makers in the field of liver transplantation when facing specifc problems by synthesizing evidence, comprising all relevant options, generalizing results to other contexts, extending the time horizon and exploring the uncertainty. For modeling studies of economic evaluation for transplantation, understanding the current nature of the disease is crucial, as well as the selection of appropriate modelling techniques. The quality and availability of data is another key element for the selection and development of decision analytical models. In addition, good practice guidelines should be complied, which is important for standardization and comparability between economic outputs.展开更多
BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the late...BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.展开更多
文摘BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.
基金financially supported by the National Key Research and Development Project of the Ministry of Science and Technology of China(No.2022YFB4601000)the Fundamental Research Funds for the Central Universities(No.2042023kf0103)the Ministry of Trade,Industry and Energy,Korea(No.20013095)。
文摘The features of additive manufacturing(AM)have made commercially pure titanium(CP-Ti)an attractive candidate material for biomedical implants.However,achieving high strength and ductility is challenging because of the columnar structures and fine martensite formation.This study investigated the effect of carbon nanotubes(CNTs)addition on the microstructure and mechanical properties of grade 1 CP-Ti(Gr-1)during the laser powder bed fusion(L-PBF)process.A minute amount of 0.2%mass fraction(wt%)CNTs addition resulted in a high yield strength of approximately 700 MPa and exceptional ductility of 25.7%.Therein,a portion of the CNTs dissolved in the matrix as solute atoms,contributing to solution strengthening,while others were transformed into Ti C_(x)through an in situ reaction with the Ti matrix.Furthermore,the addition of CNTs resulted in the formation of a larger fraction of equiaxed grains and increased the activity of basal and prismatic slip systems.Hence,Gr-1 with CNTs exhibited significantly increased ductility while maintaining a high strength comparable to that of Gr-1 without CNTs.The insights gained from this study provide a novel approach for designing strong and ductile Ti alloys for AM.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82173699 and 32200531)Shanghai Jiao Tong University Trans-Med Awards Research,China(STAR Project No.:20230101)Shanghai Science and Technol-ogy Commission,China(Grant No.:23DZ2290600).
文摘Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC_(50))of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal“dead ends”and“safe bets”for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogeneoxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.
基金supported by the National Natural Science Foundation of China(32322041,W2412029,32321001,32471279)USTC Research Funds of the Double First-Class Initiative(YD9100002004,YD9100002020)+2 种基金Fundamental Research Funds for the Central Universities(WK9100000031)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20230034)the Natural Science Foundation of Anhui Province(2408085JX005).
文摘Mechanosensitive ion channels are essential for sensing and converting mechanical forces into electrical or chemical signals.These channels are widely distributed across bacteria,animals,and plants.In Arabidopsis thaliana,the OSCA family has been identified as mechanically activated ion channels that respond to osmotic stress by allowing calcium ions to enter the cell.This influx increases the cytoplasmic calcium concentration,triggering osmotic stress-induced signal transduction cascades in plants.In this study,we determined the structures of OSCA2.2 and OSCA3.1 via cryoelectron microscopy(cryo-EM).Both proteins form homodimers consisting of 11 transmembrane helices(TM1–11).The ion conduction pathway is formed by TM4–8.Despite belonging to the same family,OSCA2.2 and OSCA3.1 exhibit notable structural variations.Structural analysis revealed that both OSCA2.2 and OSCA3.1 exhibit a closed conformation.We also conducted functional studies on OSCA proteins via electrophysiological experiments and confirmed the role of key amino acids in the process of ion permeation.
基金Supported by the National Natural Science Foundation of China(21775114,21874102)。
文摘Silver ion(Ag^(+))is a highly toxic metal ion,and its monitoring in water or food resources has become extraordinarily necessary within the scope of human health.In the light of the fact of Ag^(+)-induced folding structure of specific peptides,an unlabeled and highselectivity Ag^(+)assay is presented by means of intrinsic fluorescence of peptides.Under the quenching effect of gold nanoparticles(AuNPs),characteristic fluorescence of peptides could be considerably reduced by rapid modification.Along with the Ag adding,the fluorescence signals of peptide-AuNPs are largely enhanced by the behavior between peptides and Agt.This is basically involving the formation of 4-coordinated complexes,generating the changes of peptides in structure and fluorescence properties.Under this circumstance,the adverse influence of plenty of interfering ions is suppressed,including the toxic Hg^(2+),Pb^(2+).The results highlight that Ag ions could be selectively recognized as low as 2.4 nmol/L with a linear range of 5 to 800 nmol/L.In comparison with other programs,the given approach declares simplicity,sensitivity,and superior selectivity.Furthermore,the biosensor excels in the practical application in water samples(e.g.,lake,tap and drinking water)owing to its non-interference and on-site rapid determination.
基金supported by Sichuan University AI-Driven In-novative Experimental Technology Research Project(SCU2025047).
文摘With the development of education and technology,the construction of research public platforms has emerged as a critical initiative for many universities and top-tier public hospitals.The core and most fundamental function of a basic public platform is to aggregate large instruments and specific resources,providing open services for instrumental analysis and sample testing.Optimized management and high-quality,efficient services are essential for such platforms.This article elucidates the construction of a research public platform in West China Hospital,focusing on the adoption of hierarchical management and precise services.The core of the hierarchical management lies in building a multi-level service platform composed of routine support platforms,advanced technology platforms,and specially qualification platforms,while establishing a talent hierarchy that differentiates between core and routine positions.This structure is designed to accurately meet the diverse needs of users and enhance resource efficiency.By implementing user access control with differentiated permissions for internal and external users and a dynamic credit-based review system,the laboratory can ensure safe and efficient operations.The four service modes—instrument usage,in-lab experiments,sample testing,and collaborative projects—are precisely aligned with various research scenarios.Proactive engagement with grant-funded projects,customized services for research groups,and a multidimensional training system further strengthen the platform's support for major scientific research tasks.Through systematic management and service innovation,this model achieves efficient integration and sustainable development of platform resources,providing a valuable reference for the construction of public platforms in similar medical institutions.
基金supported by the National Natural Science Foundation of China(No.82374158)National Science and Technology Major Project(No.2018ZX09711001-002-004)+1 种基金the Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(No.CXTD22007)the Medical and Health Technology Innovation Project(No.2022-I2M-1-020).
文摘A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing potential therapeutic targets.Here,we present an analytical strategy for the deep discovery of heterogeneous metabolism and drug response in the heart tissue of rats with HF using airflow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)coupled with bulk RNAsequencing.Spatial metabolomics illustrated pronounced metabolic heterogeneity between the infarct(I),infarct margin(IM),and non-infarct(NI)areas of heart tissue in HF.Integrated transcriptomics showed that increased mRNA expression of ATP citrate lyase disrupted the tricarboxylic acid(TCA)cycle in the NI area.Impairment of the carnitine shuttle system led to a significant accumulation of carnitines,suggesting potential abnormalities in fatty acid(FA)oxidation.Coupling on-tissue chemical derivatization with AFADESI-MSI enabled us to confirm the occurrence of incomplete oxidation of FAs in the NI area.Additionally,we observed a heterogeneous drug response between the anti-HF medications valsartan and Qishen Yiqi Dripping Pills(QDP).Valsartan exhibited a more pronounced effect on metabolic regulation in the I area,whereas QDP exerted stronger regulatory effects on metabolism in the NI area.Utilizing this method,four potential therapeutic targets were identified in HF:CPT1A,PDHB,ACLY,and BCAT2,which were preliminarily validated by western blotting.Overall,integrating spatial metabolomics with transcriptomics facilitates comprehensive analyses that link differential metabolites and genes,enabling a more precise characterization of metabolic changes in heart injury microareas and providing effective methods for elucidating molecular mechanisms and identifying potential therapeutic targets for HF.
基金supported by the National Basic Research Program of China 973 Program(Nos.2021YFA0910803,2021YFC2103900)the National Natural Science Foundation of China(No.21977011)+4 种基金the Natural Science Foundation of Guangdong Province(Nos.2022A1515010996 and 2020A1515011544)the Shenzhen Science and Technology Innovation Committee(Nos.RCJC20200714114433053,JCYJ20180507181527112 and JCYJ20200109140406047)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)the Shenzhen Fundamental Research Program(No.GXWD20201231165807007–20200827170132001)Tian Fu Jin Cheng Laboratory(Advanced Medical Center)Group Racing Project(No.TFJC2023010008)。
文摘Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.
基金supported by the National Natural Science Foundation of Jiangsu Province(BE20197310 to J-M.L.)the National Key R&D Program of China(2021YFF0702500 to J-M.L.and A-M.S.,and the Start-up Funding of Scientific Researches for Postdoc in Guangzhou,Guangdong Province to H-F.L.).
文摘Being widespread across the globe,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)keeps evolving and generating new variants and continuously poses threat to public health,especially to the population with chronic comorbidities.Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019(COVID-19).Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential.Here,in this study,we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus(db/db),and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters.SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters.Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters,and may induce serious complications such as diabetic kidney disease and cardiac lesions.Our findings demonstrated that despite the decreased respiratory pathogenicity,the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters,suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected.This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes.It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.
基金supported by the China Postdoctoral Science Foundation(Nos.2023M730317 and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)+3 种基金the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)the Programs of the National Natural Science Foundation of China(No.21976050)the Science and Technology Program of Hebei Province(No.21377779D)the Natural Science Foundation of Hebei Province,China(No.B2020206008).
文摘Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly diagnosed acute coronary syndrome(ACS)patients and detected seven myocardial enzymes and six kidney function biomarkers.Twelve PFASwere also assessedwith ultra-high-performance liquid chromatography-tandem mass spectrometry.Generalized linear model and restricted cubic spline model were applied to single pollutant analysis.Quantile g-computation was used for mixture analysis.Network model was utilized to identify central and bridge nodes of pollutants and phenotypes.In the present study,perfluorohexane sulfonic acid was positively associated with uric acid(UA)(β=0.04,95%confidence interval(CI):0.01,0.07),and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate(β=-0.04,95%CI:-0.07,-0.01)but positively associated with UA(β=0.03,95%CI:0.01,0.06).In mixture analysis,each quantile increase in the PFAS mixture was significantly associated with UA(β=0.08,95%CI:0.04,0.11).Network analysis revealed that perfluorooctanoate,UA,and myoglobin were denoted as bridge nodes,and the first principal component of lactate dehydrogenase and creatine kinase-myocardial band was identified as the node with the highest strength and expected influence.This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network,which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.
基金National Natural Science Foundation of China (NSFC)(52273266, U2001216)Shenzhen Science and Technology Innovation Committee (20231121102401001)+2 种基金Shenzhen Key Laboratory Project (ZDSYS201602261933302)GuangdongHong Kong-Macao Joint Laboratory on Micro-Nano Manufacturing Technology (2021LSYS004)SUSTech high level special funds (G03050K002)。
文摘Widely used spin-coated nickle oxide (NiOx) based perovskite solar cells often suffer from severe interfacial reactions between the NiOxand adjacent perovskite layers due to surface defect states,which inherently impair device performance in a long-term view,even with surface molecule passivation.In this study,we developed high-quality magnetron-sputtered NiOxthin films through detailed process optimization,and compared systematically sputtered and spin-coated NiOxthin film surfaces from materials to devices.These sputtered NiOxfilms exhibit improved crystallinity,smoother surfaces,and significantly reduced Ni3+or Ni vacancies compared to their spin-coated counterparts.Consequently,the interface between the perovskite and sputtered NiOxfilm shows a substantially reduced density of defect states.Perovskite solar cells (PSCs) fabricated with our optimally sputtered NiOxfilms achieved a high power conversion efficiency (PCE) of up to 19.93%and demonstrated enhanced stability,maintaining 86.2% efficiency during 500 h of maximum power point tracking under one standard sun illumination.Moreover,with the surface modification using (4-(2,7-dibromo-9,9-dimethylacridin-10(9H)-yl)butyl)p hosphonic acid (DMAcPA),the device PCE was further promoted to 23.07%,which is the highest value reported for sputtered NiOxbased PSCs so far.
基金funded by R.D.H.,P.B.,A.S.W. and Z.W,Heart Foundation Vanguard Grant#107321funded by contributions from The Baird Institute for applied Heart and Lung Research.
文摘Objective:Sheep are commonly used as large animal pre-clinical models for inves-tigating cardiovascular therapies,interventions,anatomy and physiology.Further,novel small diameter vascular grafts are frequently tested via implantation into sheep carotid arteries(CAs).This is because,unlike humans,acute occlusion of one or both sheep CAs is not associated with morbidity or mortality and thus provides safer experimental testing,with reduced ethical constraints,animal numbers and costs.However,to date there has been no evidence regarding sheep tolerance of femoral artery(FA)occlusion.Methods:In this study,seven sheep underwent CA graft surgery,with digital subtrac-tion angiography(DSA)of the CAs performed every 2 months via femoral access,for a total of 8 months.Four months into the study,the left FA of two sheep became inac-cessible due to a suspected FA occlusion.Thus,femoral angiography was performed,followed by FA dissection,FA histology and retrospective analysis of both veterinar-ian animal monitoring and pain scores.Results:FA angiography and histology confirmed complete left FA occlusion in two sheep.Retrospective animal monitoring demonstrated sheep with occluded FAs did not display increased pain scores or deleterious effects on their gait or wellbeing.Conclusion:Our data shows that sheep tolerate FA occlusion with no symptoms,similar to their cerebral circulation,making them an appropriate model for assessing small diameter femoral graft interposition studies and testing other cardiovascular interventions.
基金the National Key Research and Development Program of China (Grant No. SQ2017YFSF090096)National Natural Science Foundation of China (Grant No. 81370855,81770756 and 81300627)+3 种基金Foundation of Science and Technology Department of Sichuan Province (Grant No. 2013SZ0006, 2015SZ0230, 2018JY0089 and 2017HH0063)1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZY2016104)Youth Researcher Funding of Sichuan University (Grant No. 2017SCU11042 and 2017SCU04A17)Research Funding of Sichuan Health and Family Planning Commission (Grant No. 17PJ159,18PJ434 and 18PJ453).
文摘Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.
文摘Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions.Photobiomodulation can promote neurogenesis and elicit anti-apoptotic,antiinflammatory and antioxidative responses.Its therapeutic effects have been demonstrated in studies on neurological diseases,peripheral nerve injuries,pain relief and wound healing.We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019.The NCBI PubMed database,EMBASE database,Cochrane Library and ScienceDirect database were searched.We reviewed 95 papers and analyzed.Photobiomodulation has wide applicability in the treatment of stroke,traumatic brain injury,Parkinson’s disease,Alzheimer’s disease,major depressive disorder,and other diseases.Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases.However,additional studies with adequate sample size are needed to optimize treatment parameters.
文摘AIM To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation.METHODS A total of 1607 consecutive liver transplantations were analyzed in a retrospective study. Detailed subset analysis was performed in 417 patients, which have been transplanted since the introduction of Model of End-Stage Liver Disease(MELD)-based liver allocation. Risk factors for the onset of anastomotic biliary complications were identified with multivariable binary logisticregression analyses. The identified risk factors in regression analyses were compiled into a prognostic model. The applicability was evaluated with receiver operating characteristic curve analyses. Furthermore, Kaplan-Meier analyses with the log rank test were applied where appropriate. RESULTS Biliary complications were observed in 227 cases(14.1%). Four hundred and seventeen(26%) transplantations were performed after the introduction of MELD-based donor organ allocation. Since then, 21%(n = 89) of the patients suffered from biliary complications, which are further categorized into anastomotic bile leaks [46%(n = 41)], anastomotic strictures [25%(n = 22)], cholangitis [8%(n = 7)] and non-anastomotic strictures [3%(n = 3)]. The remaining 18%(n = 16) were not further classified. After adjustment for all univariably significant variables, the recipient MELD-score at transplantation(P = 0.006; OR = 1.035; 95%CI: 1.010-1.060), the development of hepatic artery thrombosis post-operatively(P = 0.019; OR = 3.543; 95%CI: 1.233-10.178), as well as the donor creatinine prior to explantation(P = 0.010; OR = 1.003; 95%CI: 1.001-1.006) were revealed as independent risk factors for biliary complications. The compilation of these identified risk factors into a prognostic model was shown to have good prognostic abilities in the investigated cohort with an area under the receiver operating curve of 0.702.CONCLUSION The parallel occurrence of high recipient MELD and impaired donor kidney function should be avoided. Risk is especially increased when post-transplant hepatic artery thrombosis occurs.
基金Supported by a grant from the German Federal Ministry of Education and Research,No.01EO1302
文摘As the gap between a shortage of organs and the im-mense demand for liver grafts persists, every available donor liver needs to be optimized for utility, urgency and equity. To overcome this challenge, decision modelling might allow us to gather evidence from previous studies as well as compare the costs and consequences of alternative options. For public health policy and clinical intervention assessment, it is a potentially powerful tool. The most commonly used types of decision analytical models include decision trees, the Markov model, microsimulation, discrete event simulation and the system dynamic model. Analytic models could support decision makers in the field of liver transplantation when facing specifc problems by synthesizing evidence, comprising all relevant options, generalizing results to other contexts, extending the time horizon and exploring the uncertainty. For modeling studies of economic evaluation for transplantation, understanding the current nature of the disease is crucial, as well as the selection of appropriate modelling techniques. The quality and availability of data is another key element for the selection and development of decision analytical models. In addition, good practice guidelines should be complied, which is important for standardization and comparability between economic outputs.
文摘BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.
