BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic im...BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.展开更多
Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the J...Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.展开更多
AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.展开更多
BACKGROUND Microvascular invasion(MVI)is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma(HCC)surgery.Currently,there is a paucity of preoperative evaluation approaches for MV...BACKGROUND Microvascular invasion(MVI)is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma(HCC)surgery.Currently,there is a paucity of preoperative evaluation approaches for MVI.AIM To investigate the predictive value of texture features and radiological signs based on multiparametric magnetic resonance imaging in the non-invasive preoperative prediction of MVI in HCC.METHODS Clinical data from 97 HCC patients were retrospectively collected from January 2019 to July 2022 at our hospital.Patients were classified into two groups:MVI-positive(n=57)and MVI-negative(n=40),based on postoperative pathological results.The correlation between relevant radiological signs and MVI status was analyzed.MaZda4.6 software and the mutual information method were employed to identify the top 10 dominant texture features,which were combined with radiological signs to construct artificial neural network(ANN)models for MVI prediction.The predictive performance of the ANN models was evaluated using area under the curve,sensitivity,and specificity.ANN models with relatively high predictive performance were screened using the DeLong test,and the regression model of multilayer feedforward ANN with backpropagation and error backpropagation learning method was used to evaluate the models’stability.RESULTS The absence of a pseudocapsule,an incomplete pseudocapsule,and the presence of tumor blood vessels were identified as independent predictors of HCC MVI.The ANN model constructed using the dominant features of the combined group(pseudocapsule status+tumor blood vessels+arterial phase+venous phase)demonstrated the best predictive performance for MVI status and was found to be automated,highly operable,and very stable.CONCLUSION The ANN model constructed using the dominant features of the combined group can be recommended as a noninvasive method for preoperative prediction of HCC MVI status.展开更多
Percutaneous coronary intervention(PCI),as an essential treatment for coronary artery disease,has significantly improved the prognosis of patients with large coronary artery lesions.However,some patients continue to e...Percutaneous coronary intervention(PCI),as an essential treatment for coronary artery disease,has significantly improved the prognosis of patients with large coronary artery lesions.However,some patients continue to experience myocar-dial ischemic symptoms post-procedure,largely due to coronary microvascular dysfunction(CMD).The pathophysiological mechanisms of CMD are complex and involve endothelial dysfunction,microvascular remodeling,reperfusion in-jury,and metabolic abnormalities.Moreover,components of metabolic syndrome,including obesity,hyperglycemia,hypertension,and dyslipidemia,exacerbate the occurrence and progression of CMD through multiple pathways.This review systematically summarizes the latest research advan-cements in CMD after PCI,including its pathogenesis,diagnostic techniques,management strategies,and future research directions.For diagnosis,invasive techniques such as coronary flow reserve and the index of microcirculatory resistance,as well as non-invasive imaging modalities(positron emission tomography and cardiac magnetic reso-nance),provide tools for early CMD detection.In terms of management,a multi-level intervention strategy is emphasized,incorporating lifestyle modifications(diet,exercise,and weight control),pharmacotherapy(vasodilators,hypoglycemic agents,statins,and metabolic modulators),traditional Chinese medicine,and specialized treatments(enhanced external counterpulsation,metabolic surgery,and lipoprotein apheresis).However,challenges remain in CMD treatment,including limitations in diagnostic tools and the lack of personalized treatment strategies.Future research should focus on the complex interactions between CMD and metabolic risks,aiming to optimize diagnostic and therapeutic strate-gies to improve the long-term prognosis of patients post-PCI.展开更多
Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to...Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to predict MVI and high-risk(M2)status in HBV-related HCC using contrast-enhanced computed tomography(CECT)radiomics and clinicoradiological factors.The study analyzed 270 patients,creating models that achieved an area under the curve values of 0.841 and 0.768 for MVI prediction,and 0.865 and 0.798 for M2 status prediction in training and validation datasets,respectively.These results are comparable to previous radiomics-based approaches,which reinforces the potential of this method in MVI prediction.The strengths of the study include its focus on HBV-related HCC and the use of widely accessible CECT imaging.However,limitations,such as retrospective design and manual segmentation,highlight areas for improvement.The editorial discusses the implications of the study including the need for standardized radiomics approaches and the potential impact on personalized treatment strategies.It also suggests future research directions,such as exploring mechanistic links between radiomics features and MVI,as well as integrating additional biomarkers or imaging modalities.Overall,this study contributes significantly to HCC management,paving the way for more accurate,personalized treatment approaches in the era of precision oncology.展开更多
Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,p...Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.展开更多
Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvas...Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.展开更多
Background:Hepatocellular carcinoma(HCC)recurrence following liver transplantation(LT)remains a major challenge.This study aimed to investigate the effect of adjuvant chemotherapy(ACT)with the modified FOLFOX-6(mFOLFO...Background:Hepatocellular carcinoma(HCC)recurrence following liver transplantation(LT)remains a major challenge.This study aimed to investigate the effect of adjuvant chemotherapy(ACT)with the modified FOLFOX-6(mFOLFOX-6)regimen on the post-transplant prognosis of HCC patients.Methods:HCC patients who underwent LT at our institution from June 2017 to December 2019 were enrolled.The cohort was divided into the ACT group(n=57)and the non-ACT group(n=93).The median post-transplant follow-up period was 54.0 months.The study endpoints were HCC recurrence and patient mortality following LT.The association between ACT and recurrence/mortality were evaluated through univariate and multivariate analyses utilizing a Cox proportional hazards model,propensity score adjustment,propensity score matching,and inverse probability of treatment weighting(IPTW)analyses.A stratification analysis was performed to determine the interaction effects.Results:The ACT group was younger and had worse tumor characteristics including tumor number,tu-mor size,portal vein tumor thrombosis,pathological differentiation and microvascular invasion(MVI).The ACT group also demonstrated a lower risk of mortality than the non-ACT group(hazard ratio=0.36,P=0.017).It was consistent across sensitivity analyses utilizing propensity score adjustment and match-ing.There was a significant stronger association between ACT and recurrence-free benefit in patients with grade M2 of MVI compared to patients with grade M0/1(P for interaction=0.002).Conclusions:ACT with mFOLFOX-6 regimen decreased the recurrence and mortality risks following LT for HCC patients.ACT may be considered in HCC patients with high risk of recurrence and mortality after LT.展开更多
BACKGROUND Microvascular invasion(MVI)is an important prognostic factor in hepatocellular carcinoma(HCC),but its preoperative prediction remains challenging.AIM To develop and validate a 2.5-dimensional(2.5D)deep lear...BACKGROUND Microvascular invasion(MVI)is an important prognostic factor in hepatocellular carcinoma(HCC),but its preoperative prediction remains challenging.AIM To develop and validate a 2.5-dimensional(2.5D)deep learning-based multiinstance learning(MIL)model(MIL signature)for predicting MVI in HCC,evaluate and compare its performance against the radiomics signature and clinical signature,and assess its prognostic predictive value in both surgical resection and transcatheter arterial chemoembolization(TACE)cohorts.METHODS A retrospective cohort consisting of 192 patients with pathologically confirmed HCC was included,of whom 68 were MVI-positive and 124 were MVI-negative.The patients were randomly assigned to a training set(134 patients)and a validation set(58 patients)in a 7:3 ratio.An additional 45 HCC patients undergoing TACE treatment were included in the TACE validation cohort.A modeling strategy based on computed tomography arterial phase images was implemented,utilizing 2.5D deep learning in combination with a MIL framework for the prediction of MVI in HCC.Moreover,this method was compared with the radiomics signature and clinical signatures,and the predictive performance of the various models was evaluated using receiver operating characteristic curves and decision curve analysis(DCA),with DeLong’s test applied to compare the area under the curve(AUC)between models.Kaplan-Meier curves were utilized to analyze differences in recurrence-free survival(RFS)or progression-free survival(PFS)among different HCC treatment cohorts stratified by MIL signature risk.RESULTS MIL signature demonstrated superior performance in the validation set(AUC=0.877),significantly surpassing the radiomics signature(AUC=0.727,P=0.047)and clinical signature(AUC=0.631,P=0.004).DCA curves indicated that the MIL signature provided a greater clinical net benefit across the full spectrum of risk thresholds.In the prognostic analysis,high-and low-risk groups stratified by the MIL signature exhibited significant differences in RFS within the surgical resection cohort(training set P=0.0058,validation set P=0.031)and PFS within the TACE treatment cohort(P=0.045).CONCLUSION MIL signature demonstrates more accurate MVI prediction in HCC,surpassing radiomics signature and clinical signature,and offers precise prognostic stratification,thereby providing new technical support for personalized HCC treatment strategies.展开更多
Objective:Microvascular decompression(MVD)is the gold standard for treating drug-resistant classic trigeminal neuralgia(dcTN),with endoscopy enhancing surgical precision through improved visualization.This study evalu...Objective:Microvascular decompression(MVD)is the gold standard for treating drug-resistant classic trigeminal neuralgia(dcTN),with endoscopy enhancing surgical precision through improved visualization.This study evaluates the efficacy of fully endoscopic MVD for dcTN and presents our early experience.Methods:This retrospective study included patients with dcTN who underwent fully endoscopic MVD in the Department of Neurosurgery,the First Affiliated Hospital,Zhejiang University School of Medicine from November 2020 to February 2023.We recorded basic patient clinical information,clinical outcomes,offending vessels,complications,and recurrences,and assessed outcomes via the Barrow Neurological Institute(BNI)pain intensity score and the numeric rating scale(NRS)score.Results:All 42 patients had dcTN with preoperative BNI scores of V and NRS scores of 8e10.Endoscopic visualization enabled the precise identification of neurovascular conflicts,including small and deeply located vessels.Immediately after surgery,90.5%of patients achieved complete pain relief(BNI score of I,NRS score of 0).At the final follow-up,85.7%of patients had complete pain relief.All patients’pain was significantly relieved at immediate after surgery(0 vs.9,p<0.001)and at the final follow-up(0 vs.9,p<0.001),with lower NRS scores.Complications,including vertigo,headache,and transient facial numbness,occurred in 14.4%of patients and were manageable.展开更多
AIM:To systematically evaluate the association between nailfold capillaroscopic findings and diabetic retinopathy(DR)and compare findings in diabetic patients with and without DR.METHODS:PubMed,Web of Science,and Emba...AIM:To systematically evaluate the association between nailfold capillaroscopic findings and diabetic retinopathy(DR)and compare findings in diabetic patients with and without DR.METHODS:PubMed,Web of Science,and Embase databases were searched from inception to February 2024.The quality of the included studies was evaluated using a National Institutes of Health(NIH)Quality Assessment tool for Observational Cohort and Cross Sectional Studies.Metaanalysis was conducted to compare the findings of nailfold capillaroscopy between diabetic patients with or without DR.Subgroup analysis was employed to investigate the source of heterogeneity.RESULTS:Totally 12 studies with 1349 diabetic patients were included,of which 628 had DR.The overall quality of included studies was acceptable.Patients with DR had increased arteriolar diameters[mean difference(MD):2.68,95%confidence interval(CI):0.64-4.72]and a higher risk of developing nailfold capillaroscopic abnormalities,including bushy capillaries[odds ratio(OR):2.82,95%CI:1.65-4.80],neoformation(OR:4.61,95%CI:3.15-6.76),megacapillaries(OR:8.37,95%CI:5.07-13.80),tortuosity(OR:7.29,95%CI:2.76-19.22),microhemorrhages(OR:6.16,95%CI:2.48-15.26),meandering capillaries(OR:4.68,95%CI:1.05-20.80)and avascular areas(OR:7.92,95%CI:2.68-23.38).The presence of tortuous capillary was more common in DR in India than in Turkey,while avascular area in the nailfolds was linked to DR only in India(OR:11.28,95%CI:3.91-32.60).Among the nailfold capillaroscopic abnormalities,tortuosity,microhemorrhage,and meandering capillary showed no significant correlation with the severity of DR,except for avascular area(P=0.04).CONCLUSION:There are significant associations between nailfold capillaroscopic findings and the presence of DR,supporting its potential as a non-invasive technique for monitoring microvascular changes in diabetic patients.However,further research is needed to validate its utility as an early screening tool for microvascular complications in diabetes.展开更多
BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate t...BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging(WSI)for better MVI detection.METHODS We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models.The entire tumor-containing liver lobe was subsequently obtained,following which five different sampling protocols(A-E)were employed to evaluate the detection rate,accuracy,quantity,and distribution of MVI,with the aim of identifying the optimal sampling method.RESULTS VX2 liver tumor models were successfully established in 37 rabbits,with an incidence of MVI of 81.1%(30/37).The detection rates[27%(10/37),43%(16/37),62%(23/37),68%(25/37),and 93%(14/15)]and quantity(15,36,107,125,and 395)of MVI increased significantly from protocols A to E.The distribution of MVI showed fewer MVIs farther away from the tumor,but the percentage of MVI detected quantity gradually increased from 6.7%to 48.3%in the distant nonneoplastic liver tissue from protocols A to E.Protocol C was identified as the optimal sampling method by comparing them in sequence.The sampling protocol of three consecutive interval WSIs at the tumor center(WSI3)was further screened to determine the optimal number of WSIs.Protocol A(7-point sampling method)exhibited only 46%accuracy and a high false-negative rate of 67%.Notably,the WSI3 protocol improved the accuracy to 78%and decreased the false-negative rate to 27%.CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI detection.In contrast,the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy,which is crucial for hepatocellular carcinoma diagnosis and treatment planning.展开更多
Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance,often leading to severe complications.Hemogram markers have attracted great attention from researcher...Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance,often leading to severe complications.Hemogram markers have attracted great attention from researchers for their established role in inflammatory conditions.In this respect,T2DM and its mi-crovascular complications are characterized by high inflammatory burden.Hence,recent studies in the literature have reported an association between T2DM and hemogram-derived markers.Emerging evidence highlights the utility of hemo-gram-derived markers,including the neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,red cell distribution width,and mean platelet volume,as potential predictors of T2DM onset and progression.These markers,readily available from routine hemogram tests,offer valuable insights into the systemic inflammation and vascular changes associated with T2DM and its complications,such as cardiovascular disease,nephropathy,and retinopathy.This review syn-thesizes current research on the association between hemogram-derived markers and T2DM,emphasizing their prognostic value in predicting disease severity and complications.We also explore the underlying pathophysiological mechanisms linking these markers to inflammation and metabolic dysfunction.The findings suggest that hemogram-derived markers could serve as cost-effective,non-invasive tools for risk stratification and early intervention in T2DM management.Future research should focus on standardizing reference ranges and validating these markers in diverse populations to enhance their clinical utility.展开更多
This paper highlights the innovative approach and findings of the recently published study by Xu et al,which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative predict...This paper highlights the innovative approach and findings of the recently published study by Xu et al,which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative prediction of microvascular invasion in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).The study’s use of contrast-enhanced computed tomography radiomics to construct predictive models offers a significant advancement in the surgical planning and management of HBV-HCC,potentially transforming patient outcomes through more personalized treatment strategies.This editorial commends the study's contribution to precision medicine and discusses its implic-ations for future research and clinical practice.展开更多
BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the import...BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM)is the leading cause of cardiovascular diseaserelated mortality.Farrerol(FA)possesses anti-inflammatory and antioxidant properties.However,its role in regulating endothelial ferr...BACKGROUND Diabetic cardiomyopathy(DCM)is the leading cause of cardiovascular diseaserelated mortality.Farrerol(FA)possesses anti-inflammatory and antioxidant properties.However,its role in regulating endothelial ferroptosis in DCM remains unknown.AIM To investigate the beneficial effects of FA on cardiac microvascular dysfunction in DCM from the perspective of ferroptosis in endothelial cells(ECs).METHODS The mice were fed a high-fat diet and injected with streptozotocin to induce DCM.DCM mice were orally administered FA(10 and 40 mg/kg/day)and a tail vein injection of the miR-29b-3p mimic or inhibitor for 24 weeks.Cardiac function and myocardial fibrosis were also analyzed.Cardiac microvascular function was assessed using immunofluorescence and transmission electron microscopy.Ferroptosis was analyzed using RNA sequencing,immunofluorescence,and western blotting.RESULTS FA administration improved cardiac function,alleviated myocardial fibrosis,strengthened endothelial barrier function,suppressed endothelial inflammation,and preserved the microvascular structure in DCM mice.This improvement was associated with the inhibition of endothelial ferroptosis and downregulation of miR-29b-3p in ECs.Similar efficacy was observed after tail vein injection of the miR-29b-3p inhibitor.Inhibition of miR-29b-3p in vivo showed an anti-cardiac fibrotic effect by improving microvascular dysfunction and ferroptosis in ECs,whereas overexpression of miR-29b-3p showed the opposite effects in DCM mice.Luciferase reporter assay revealed that miR-29b-3p binds to SIRT1.In cultured ECs,FA reduced high glucose and free fatty acid(HG/FFA)-induced lipid peroxidation and ferroptosis and inhibited endothelial-mediated inflammation.However,the overexpression of miR-29b-3p partially abolished the protective effects of FA against HG/FFA-induced injury in ECs.This finding suggests that the mechanism of action of FA in improving DCM is related to the downregulation of miR-29b-3p and activation of SIRT1 expression.CONCLUSION Therefore,FA has a potential therapeutic effect on cardiac microvascular dysfunction by suppressing EC ferroptosis through the miR-29b-3p/SIRT1 axis.展开更多
Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous ma...Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous manifestations that may hold diagnostic and prognostic significance. Patients with BMES have reported localized erythema, dermal thickening, and induration overlying the affected joints, which are hypothesized to reflect microvascular compromise and inflammatory processes within the bone and adjacent soft tissues. Dermatologic signs are likely linked to regional hyperemia, venous stasis, and cytokine-mediated inflammation, paralleling the pathophysiological mechanisms underlying intraosseous edema. Elevated intraosseous pressure in BMES may disrupt local perfusion, resulting in ischemia-reperfusion injury and subsequent vascular leakage, which manifests in visible cutaneous changes. Pro-inflammatory mediators, such as interleukin-1β and vascular endothelial growth factor (VEGF), central to BMES pathogenesis, may exacerbate endothelial activation, and dermal involvement. Histopathologic studies of affected skin have revealed perivascular lymphocytic infiltration and increased dermal vascularity, further supporting the theory of a shared ischemic and inflammatory pathway between bone and skin. Although MRI remains the gold standard for BMES diagnosis, recognition of these cutaneous manifestations could expedite orthopedic referral and intervention, especially in cases where imaging is delayed or symptoms are ambiguous. Current treatment options, including bisphosphonates, prostacyclin analogs, and offloading of weight bearing, may benefit from integration with dermatologic strategies to alleviate localized cutaneous symptoms and improve patient comfort. Evaluating the molecular and vascular links between BMES and its cutaneous manifestations provides an opportunity to refine diagnostic protocols and therapeutic approaches, offering a comprehensive understanding of the systemic interplay between dermal and skeletal pathophysiology, and optimizing clinical outcomes for patients affected by BMES.展开更多
Hepatocellular carcinoma(HCC),a leading cause of cancer mortality,faces diagnostic and therapeutic challenges due to its histopathological complexity and clinical heterogeneity.Pathomics,an emerging discipline that in...Hepatocellular carcinoma(HCC),a leading cause of cancer mortality,faces diagnostic and therapeutic challenges due to its histopathological complexity and clinical heterogeneity.Pathomics,an emerging discipline that integrates artificial intelligence(AI)with quantitative pathology image analysis,aims to decode disease heterogeneity by extracting high-dimensional features from histopathological specimens.This review highlights how AI-driven pathomics has revolutionized liver cancer management through automated analysis of whole-slide images.Pathomics integrates deep learning with histopathological features to enable precise tumour classification(e.g.,HCC vs cholangiocarcinoma),microvascular invasion(MVI)detection,recurrence risk stratification,and survival prediction.Advanced frameworks such as MVI-AI diagnostic model and CHOWDER demonstrate high accuracy in identifying prognostic biomarkers,whereas multiomics integration links morphometric patterns to molecular signatures(e.g.,EZH2 expression and immune infiltration).Despite these breakthroughs,critical bottlenecks persist,including limited multicentre validation studies,"black box"model interpretability,and clinical workflow integration.Future studies should emphasize AI-enhanced multimodal fusion(radiogenomics and liquid biopsy)and standardized platforms to bridge computational pathology and precision oncology,ultimately improving personalized therapeutic strategies for liver malignancies.This synthesis aims to guide research translation and advance personalized therapeutic strategies for liver malignancies.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM),driven by insulin resistance and β cell dysfunction,necessitates reliable assessment of β cell function.C-peptide(CP)measurement,a stable marker of endogenous insulin secret...BACKGROUND Type 2 diabetes mellitus(T2DM),driven by insulin resistance and β cell dysfunction,necessitates reliable assessment of β cell function.C-peptide(CP)measurement,a stable marker of endogenous insulin secretion,is useful for this clinically as it avoids interference from exogenous insulin.While fasting CP(FCP)and postprandial CP(PCP),along with glucose-adjusted indices and ratios,such as FCP/fasting plasma glucose(FPG),2 hours postprandial CP(2hCP)/postprandial blood glucose(PBG)and CP ratio,are used,their comparative efficacy in reflectingβcell function remains unclear.Hemoglobin A1c(HbA1c),a key glycemic control indicator,theoretically linksβcell function to complications,but limited studies have explored the associations between diverse CP indices,HbA1c,and diabetic microvascular complications.AIM To investigate the relationships between different CP indices and HbA1c as well as diabetic microvascular complications in T2DM.METHODS T2DM patients admitted to Department of Endocrinology at Beijing Hospital between July 1,2021 and December 31,2021 were included in the study.Clinical and laboratory data were collected,including CP levels,glucose levels,HbA1c levels and diabetic microvascular complications.Statistical analysis was performed using Statistical Package for the Social Sciences 24.0.RESULTS A total of 453 patients were included in the final analysis.Adjusted by confounding factors,CP ratio and CP/blood glucose(BG)ratio were not relevant to HbA1c,but FCP,2hCP,delta CP,FCP/FPG,2hCP/PBG and delta CP/BG were still negatively correlated to HbA1c,of which 2hCP/PBG showed the strongest negative correlation(r=-0.485,P<0.001).Independent of HbA1c and other confounding factors,2hCP,2hCP/PBG,delta CP and delta CP/BG were protective factors of diabetic retinopathy while 2hCP,delta CP and FCP/FPG were protective factors of diabetic peripheral neuropathy.CONCLUSION This study indicates that higher levels of CP indices suggest better glucose control and a lower prevalence of diabetic microvascular complications,and PCP indices,particularly 2hCP/PBG,were more relevant to HbA1c and diabetic microvascular complications than FCP indices.These results suggest CP-related indices could be useful biomarkers for diabetes management,warranting further research.展开更多
文摘BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.
文摘Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
基金Supported by the National Natural Science Foundation of China,No.81560278the Health Commission of Guangxi Zhuang Autonomous Region,No.Z20200953,No.G201903023,and No.Z-A20221157Scientific Research and Technology Development Project of Nanning,No.20213122.
文摘BACKGROUND Microvascular invasion(MVI)is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma(HCC)surgery.Currently,there is a paucity of preoperative evaluation approaches for MVI.AIM To investigate the predictive value of texture features and radiological signs based on multiparametric magnetic resonance imaging in the non-invasive preoperative prediction of MVI in HCC.METHODS Clinical data from 97 HCC patients were retrospectively collected from January 2019 to July 2022 at our hospital.Patients were classified into two groups:MVI-positive(n=57)and MVI-negative(n=40),based on postoperative pathological results.The correlation between relevant radiological signs and MVI status was analyzed.MaZda4.6 software and the mutual information method were employed to identify the top 10 dominant texture features,which were combined with radiological signs to construct artificial neural network(ANN)models for MVI prediction.The predictive performance of the ANN models was evaluated using area under the curve,sensitivity,and specificity.ANN models with relatively high predictive performance were screened using the DeLong test,and the regression model of multilayer feedforward ANN with backpropagation and error backpropagation learning method was used to evaluate the models’stability.RESULTS The absence of a pseudocapsule,an incomplete pseudocapsule,and the presence of tumor blood vessels were identified as independent predictors of HCC MVI.The ANN model constructed using the dominant features of the combined group(pseudocapsule status+tumor blood vessels+arterial phase+venous phase)demonstrated the best predictive performance for MVI status and was found to be automated,highly operable,and very stable.CONCLUSION The ANN model constructed using the dominant features of the combined group can be recommended as a noninvasive method for preoperative prediction of HCC MVI status.
文摘Percutaneous coronary intervention(PCI),as an essential treatment for coronary artery disease,has significantly improved the prognosis of patients with large coronary artery lesions.However,some patients continue to experience myocar-dial ischemic symptoms post-procedure,largely due to coronary microvascular dysfunction(CMD).The pathophysiological mechanisms of CMD are complex and involve endothelial dysfunction,microvascular remodeling,reperfusion in-jury,and metabolic abnormalities.Moreover,components of metabolic syndrome,including obesity,hyperglycemia,hypertension,and dyslipidemia,exacerbate the occurrence and progression of CMD through multiple pathways.This review systematically summarizes the latest research advan-cements in CMD after PCI,including its pathogenesis,diagnostic techniques,management strategies,and future research directions.For diagnosis,invasive techniques such as coronary flow reserve and the index of microcirculatory resistance,as well as non-invasive imaging modalities(positron emission tomography and cardiac magnetic reso-nance),provide tools for early CMD detection.In terms of management,a multi-level intervention strategy is emphasized,incorporating lifestyle modifications(diet,exercise,and weight control),pharmacotherapy(vasodilators,hypoglycemic agents,statins,and metabolic modulators),traditional Chinese medicine,and specialized treatments(enhanced external counterpulsation,metabolic surgery,and lipoprotein apheresis).However,challenges remain in CMD treatment,including limitations in diagnostic tools and the lack of personalized treatment strategies.Future research should focus on the complex interactions between CMD and metabolic risks,aiming to optimize diagnostic and therapeutic strate-gies to improve the long-term prognosis of patients post-PCI.
文摘Microvascular invasion(MVI)is a critical factor in hepatocellular carcinoma(HCC)prognosis,particularly in hepatitis B virus(HBV)-related cases.This editorial examines a recent study by Xu et al who developed models to predict MVI and high-risk(M2)status in HBV-related HCC using contrast-enhanced computed tomography(CECT)radiomics and clinicoradiological factors.The study analyzed 270 patients,creating models that achieved an area under the curve values of 0.841 and 0.768 for MVI prediction,and 0.865 and 0.798 for M2 status prediction in training and validation datasets,respectively.These results are comparable to previous radiomics-based approaches,which reinforces the potential of this method in MVI prediction.The strengths of the study include its focus on HBV-related HCC and the use of widely accessible CECT imaging.However,limitations,such as retrospective design and manual segmentation,highlight areas for improvement.The editorial discusses the implications of the study including the need for standardized radiomics approaches and the potential impact on personalized treatment strategies.It also suggests future research directions,such as exploring mechanistic links between radiomics features and MVI,as well as integrating additional biomarkers or imaging modalities.Overall,this study contributes significantly to HCC management,paving the way for more accurate,personalized treatment approaches in the era of precision oncology.
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2022MS080572022 Autonomous Region Medical and Health Science and Technology Plan Projects,No.202202190.
文摘Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.
基金supported the National Natural Science Foundation of China(81930113).
文摘Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.
基金supported by grants from Zhejiang Provincial Natural Science Foundation of China(LTGY24H030006)Re-search Project of Jinan Microecological Biomedicine Shandong Lab-oratory(JNL-2022015B).
文摘Background:Hepatocellular carcinoma(HCC)recurrence following liver transplantation(LT)remains a major challenge.This study aimed to investigate the effect of adjuvant chemotherapy(ACT)with the modified FOLFOX-6(mFOLFOX-6)regimen on the post-transplant prognosis of HCC patients.Methods:HCC patients who underwent LT at our institution from June 2017 to December 2019 were enrolled.The cohort was divided into the ACT group(n=57)and the non-ACT group(n=93).The median post-transplant follow-up period was 54.0 months.The study endpoints were HCC recurrence and patient mortality following LT.The association between ACT and recurrence/mortality were evaluated through univariate and multivariate analyses utilizing a Cox proportional hazards model,propensity score adjustment,propensity score matching,and inverse probability of treatment weighting(IPTW)analyses.A stratification analysis was performed to determine the interaction effects.Results:The ACT group was younger and had worse tumor characteristics including tumor number,tu-mor size,portal vein tumor thrombosis,pathological differentiation and microvascular invasion(MVI).The ACT group also demonstrated a lower risk of mortality than the non-ACT group(hazard ratio=0.36,P=0.017).It was consistent across sensitivity analyses utilizing propensity score adjustment and match-ing.There was a significant stronger association between ACT and recurrence-free benefit in patients with grade M2 of MVI compared to patients with grade M0/1(P for interaction=0.002).Conclusions:ACT with mFOLFOX-6 regimen decreased the recurrence and mortality risks following LT for HCC patients.ACT may be considered in HCC patients with high risk of recurrence and mortality after LT.
基金Supported by the National Natural Science Foundation of China,No.81560278The“Summit Plan(New Departure)”Project for the Development of Doctoral Degree Authorization Points and Professional Disciplines at the Affiliated Hospital of Youjiang Medical University for Nationalities,No.DF20244433+1 种基金Self-funded Research Project by the Guangxi Health and Wellness Committee,No.ZL20240824 and No.Z-L20240834The Project to Enhance the Research Foundations of Young and Mid-career Faculty in Guangxi Universities,No.2024KY0562 and No.2024KY0559。
文摘BACKGROUND Microvascular invasion(MVI)is an important prognostic factor in hepatocellular carcinoma(HCC),but its preoperative prediction remains challenging.AIM To develop and validate a 2.5-dimensional(2.5D)deep learning-based multiinstance learning(MIL)model(MIL signature)for predicting MVI in HCC,evaluate and compare its performance against the radiomics signature and clinical signature,and assess its prognostic predictive value in both surgical resection and transcatheter arterial chemoembolization(TACE)cohorts.METHODS A retrospective cohort consisting of 192 patients with pathologically confirmed HCC was included,of whom 68 were MVI-positive and 124 were MVI-negative.The patients were randomly assigned to a training set(134 patients)and a validation set(58 patients)in a 7:3 ratio.An additional 45 HCC patients undergoing TACE treatment were included in the TACE validation cohort.A modeling strategy based on computed tomography arterial phase images was implemented,utilizing 2.5D deep learning in combination with a MIL framework for the prediction of MVI in HCC.Moreover,this method was compared with the radiomics signature and clinical signatures,and the predictive performance of the various models was evaluated using receiver operating characteristic curves and decision curve analysis(DCA),with DeLong’s test applied to compare the area under the curve(AUC)between models.Kaplan-Meier curves were utilized to analyze differences in recurrence-free survival(RFS)or progression-free survival(PFS)among different HCC treatment cohorts stratified by MIL signature risk.RESULTS MIL signature demonstrated superior performance in the validation set(AUC=0.877),significantly surpassing the radiomics signature(AUC=0.727,P=0.047)and clinical signature(AUC=0.631,P=0.004).DCA curves indicated that the MIL signature provided a greater clinical net benefit across the full spectrum of risk thresholds.In the prognostic analysis,high-and low-risk groups stratified by the MIL signature exhibited significant differences in RFS within the surgical resection cohort(training set P=0.0058,validation set P=0.031)and PFS within the TACE treatment cohort(P=0.045).CONCLUSION MIL signature demonstrates more accurate MVI prediction in HCC,surpassing radiomics signature and clinical signature,and offers precise prognostic stratification,thereby providing new technical support for personalized HCC treatment strategies.
基金supported by financial assistance from the Zhejiang Provincial Natural Science Foundation of China under Grant No.LY18H160020.
文摘Objective:Microvascular decompression(MVD)is the gold standard for treating drug-resistant classic trigeminal neuralgia(dcTN),with endoscopy enhancing surgical precision through improved visualization.This study evaluates the efficacy of fully endoscopic MVD for dcTN and presents our early experience.Methods:This retrospective study included patients with dcTN who underwent fully endoscopic MVD in the Department of Neurosurgery,the First Affiliated Hospital,Zhejiang University School of Medicine from November 2020 to February 2023.We recorded basic patient clinical information,clinical outcomes,offending vessels,complications,and recurrences,and assessed outcomes via the Barrow Neurological Institute(BNI)pain intensity score and the numeric rating scale(NRS)score.Results:All 42 patients had dcTN with preoperative BNI scores of V and NRS scores of 8e10.Endoscopic visualization enabled the precise identification of neurovascular conflicts,including small and deeply located vessels.Immediately after surgery,90.5%of patients achieved complete pain relief(BNI score of I,NRS score of 0).At the final follow-up,85.7%of patients had complete pain relief.All patients’pain was significantly relieved at immediate after surgery(0 vs.9,p<0.001)and at the final follow-up(0 vs.9,p<0.001),with lower NRS scores.Complications,including vertigo,headache,and transient facial numbness,occurred in 14.4%of patients and were manageable.
基金Supported by University-Industry Collaborative Education Program of the Ministry of Education(No.231104794161945,No.230700562265543)Engineering Research Center of Integration and Application of Digital Learning Technology,Ministry of Education(No.1311016)+2 种基金Supply and Demand Job Matching and Student Development Program of Ministry of Education(No.2024011802142)Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program(No.202410304127Y)the Science and Technology Project of Nantong City(No.MS2023050).
文摘AIM:To systematically evaluate the association between nailfold capillaroscopic findings and diabetic retinopathy(DR)and compare findings in diabetic patients with and without DR.METHODS:PubMed,Web of Science,and Embase databases were searched from inception to February 2024.The quality of the included studies was evaluated using a National Institutes of Health(NIH)Quality Assessment tool for Observational Cohort and Cross Sectional Studies.Metaanalysis was conducted to compare the findings of nailfold capillaroscopy between diabetic patients with or without DR.Subgroup analysis was employed to investigate the source of heterogeneity.RESULTS:Totally 12 studies with 1349 diabetic patients were included,of which 628 had DR.The overall quality of included studies was acceptable.Patients with DR had increased arteriolar diameters[mean difference(MD):2.68,95%confidence interval(CI):0.64-4.72]and a higher risk of developing nailfold capillaroscopic abnormalities,including bushy capillaries[odds ratio(OR):2.82,95%CI:1.65-4.80],neoformation(OR:4.61,95%CI:3.15-6.76),megacapillaries(OR:8.37,95%CI:5.07-13.80),tortuosity(OR:7.29,95%CI:2.76-19.22),microhemorrhages(OR:6.16,95%CI:2.48-15.26),meandering capillaries(OR:4.68,95%CI:1.05-20.80)and avascular areas(OR:7.92,95%CI:2.68-23.38).The presence of tortuous capillary was more common in DR in India than in Turkey,while avascular area in the nailfolds was linked to DR only in India(OR:11.28,95%CI:3.91-32.60).Among the nailfold capillaroscopic abnormalities,tortuosity,microhemorrhage,and meandering capillary showed no significant correlation with the severity of DR,except for avascular area(P=0.04).CONCLUSION:There are significant associations between nailfold capillaroscopic findings and the presence of DR,supporting its potential as a non-invasive technique for monitoring microvascular changes in diabetic patients.However,further research is needed to validate its utility as an early screening tool for microvascular complications in diabetes.
基金Supported by the National Natural Science Foundation of China,No.82072038 and No.82371975.
文摘BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains uncertain.AIM To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging(WSI)for better MVI detection.METHODS We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models.The entire tumor-containing liver lobe was subsequently obtained,following which five different sampling protocols(A-E)were employed to evaluate the detection rate,accuracy,quantity,and distribution of MVI,with the aim of identifying the optimal sampling method.RESULTS VX2 liver tumor models were successfully established in 37 rabbits,with an incidence of MVI of 81.1%(30/37).The detection rates[27%(10/37),43%(16/37),62%(23/37),68%(25/37),and 93%(14/15)]and quantity(15,36,107,125,and 395)of MVI increased significantly from protocols A to E.The distribution of MVI showed fewer MVIs farther away from the tumor,but the percentage of MVI detected quantity gradually increased from 6.7%to 48.3%in the distant nonneoplastic liver tissue from protocols A to E.Protocol C was identified as the optimal sampling method by comparing them in sequence.The sampling protocol of three consecutive interval WSIs at the tumor center(WSI3)was further screened to determine the optimal number of WSIs.Protocol A(7-point sampling method)exhibited only 46%accuracy and a high false-negative rate of 67%.Notably,the WSI3 protocol improved the accuracy to 78%and decreased the false-negative rate to 27%.CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI detection.In contrast,the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy,which is crucial for hepatocellular carcinoma diagnosis and treatment planning.
文摘Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance,often leading to severe complications.Hemogram markers have attracted great attention from researchers for their established role in inflammatory conditions.In this respect,T2DM and its mi-crovascular complications are characterized by high inflammatory burden.Hence,recent studies in the literature have reported an association between T2DM and hemogram-derived markers.Emerging evidence highlights the utility of hemo-gram-derived markers,including the neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,red cell distribution width,and mean platelet volume,as potential predictors of T2DM onset and progression.These markers,readily available from routine hemogram tests,offer valuable insights into the systemic inflammation and vascular changes associated with T2DM and its complications,such as cardiovascular disease,nephropathy,and retinopathy.This review syn-thesizes current research on the association between hemogram-derived markers and T2DM,emphasizing their prognostic value in predicting disease severity and complications.We also explore the underlying pathophysiological mechanisms linking these markers to inflammation and metabolic dysfunction.The findings suggest that hemogram-derived markers could serve as cost-effective,non-invasive tools for risk stratification and early intervention in T2DM management.Future research should focus on standardizing reference ranges and validating these markers in diverse populations to enhance their clinical utility.
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06。
文摘This paper highlights the innovative approach and findings of the recently published study by Xu et al,which underscores the integration of radiomics and clinicoradiological factors to enhance the preoperative prediction of microvascular invasion in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).The study’s use of contrast-enhanced computed tomography radiomics to construct predictive models offers a significant advancement in the surgical planning and management of HBV-HCC,potentially transforming patient outcomes through more personalized treatment strategies.This editorial commends the study's contribution to precision medicine and discusses its implic-ations for future research and clinical practice.
基金Supported by the Instituto de Salud Carlos Ⅲ(ISCⅢ)Through the Project Co-Funded by the European Union,No.PI20-00487,No.PI23-00119 and No.PI24-01630.
文摘BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.
基金Supported by Medical Health Science and Technology Project of Zhejiang Provincial,No.2025KY1721 and No.2022KY1292Science and Technology Projects of Shaoxing City,No.2022KY104.
文摘BACKGROUND Diabetic cardiomyopathy(DCM)is the leading cause of cardiovascular diseaserelated mortality.Farrerol(FA)possesses anti-inflammatory and antioxidant properties.However,its role in regulating endothelial ferroptosis in DCM remains unknown.AIM To investigate the beneficial effects of FA on cardiac microvascular dysfunction in DCM from the perspective of ferroptosis in endothelial cells(ECs).METHODS The mice were fed a high-fat diet and injected with streptozotocin to induce DCM.DCM mice were orally administered FA(10 and 40 mg/kg/day)and a tail vein injection of the miR-29b-3p mimic or inhibitor for 24 weeks.Cardiac function and myocardial fibrosis were also analyzed.Cardiac microvascular function was assessed using immunofluorescence and transmission electron microscopy.Ferroptosis was analyzed using RNA sequencing,immunofluorescence,and western blotting.RESULTS FA administration improved cardiac function,alleviated myocardial fibrosis,strengthened endothelial barrier function,suppressed endothelial inflammation,and preserved the microvascular structure in DCM mice.This improvement was associated with the inhibition of endothelial ferroptosis and downregulation of miR-29b-3p in ECs.Similar efficacy was observed after tail vein injection of the miR-29b-3p inhibitor.Inhibition of miR-29b-3p in vivo showed an anti-cardiac fibrotic effect by improving microvascular dysfunction and ferroptosis in ECs,whereas overexpression of miR-29b-3p showed the opposite effects in DCM mice.Luciferase reporter assay revealed that miR-29b-3p binds to SIRT1.In cultured ECs,FA reduced high glucose and free fatty acid(HG/FFA)-induced lipid peroxidation and ferroptosis and inhibited endothelial-mediated inflammation.However,the overexpression of miR-29b-3p partially abolished the protective effects of FA against HG/FFA-induced injury in ECs.This finding suggests that the mechanism of action of FA in improving DCM is related to the downregulation of miR-29b-3p and activation of SIRT1 expression.CONCLUSION Therefore,FA has a potential therapeutic effect on cardiac microvascular dysfunction by suppressing EC ferroptosis through the miR-29b-3p/SIRT1 axis.
文摘Bone marrow edema syndrome (BMES), is a rare and self-limiting condition characterized by localized bone pain and transient marrow edema visible on MRI. BMES has been increasingly associated with specific cutaneous manifestations that may hold diagnostic and prognostic significance. Patients with BMES have reported localized erythema, dermal thickening, and induration overlying the affected joints, which are hypothesized to reflect microvascular compromise and inflammatory processes within the bone and adjacent soft tissues. Dermatologic signs are likely linked to regional hyperemia, venous stasis, and cytokine-mediated inflammation, paralleling the pathophysiological mechanisms underlying intraosseous edema. Elevated intraosseous pressure in BMES may disrupt local perfusion, resulting in ischemia-reperfusion injury and subsequent vascular leakage, which manifests in visible cutaneous changes. Pro-inflammatory mediators, such as interleukin-1β and vascular endothelial growth factor (VEGF), central to BMES pathogenesis, may exacerbate endothelial activation, and dermal involvement. Histopathologic studies of affected skin have revealed perivascular lymphocytic infiltration and increased dermal vascularity, further supporting the theory of a shared ischemic and inflammatory pathway between bone and skin. Although MRI remains the gold standard for BMES diagnosis, recognition of these cutaneous manifestations could expedite orthopedic referral and intervention, especially in cases where imaging is delayed or symptoms are ambiguous. Current treatment options, including bisphosphonates, prostacyclin analogs, and offloading of weight bearing, may benefit from integration with dermatologic strategies to alleviate localized cutaneous symptoms and improve patient comfort. Evaluating the molecular and vascular links between BMES and its cutaneous manifestations provides an opportunity to refine diagnostic protocols and therapeutic approaches, offering a comprehensive understanding of the systemic interplay between dermal and skeletal pathophysiology, and optimizing clinical outcomes for patients affected by BMES.
基金Supported by Wenzhou Municipal Science and Technology Bureau,No.Y20240109.
文摘Hepatocellular carcinoma(HCC),a leading cause of cancer mortality,faces diagnostic and therapeutic challenges due to its histopathological complexity and clinical heterogeneity.Pathomics,an emerging discipline that integrates artificial intelligence(AI)with quantitative pathology image analysis,aims to decode disease heterogeneity by extracting high-dimensional features from histopathological specimens.This review highlights how AI-driven pathomics has revolutionized liver cancer management through automated analysis of whole-slide images.Pathomics integrates deep learning with histopathological features to enable precise tumour classification(e.g.,HCC vs cholangiocarcinoma),microvascular invasion(MVI)detection,recurrence risk stratification,and survival prediction.Advanced frameworks such as MVI-AI diagnostic model and CHOWDER demonstrate high accuracy in identifying prognostic biomarkers,whereas multiomics integration links morphometric patterns to molecular signatures(e.g.,EZH2 expression and immune infiltration).Despite these breakthroughs,critical bottlenecks persist,including limited multicentre validation studies,"black box"model interpretability,and clinical workflow integration.Future studies should emphasize AI-enhanced multimodal fusion(radiogenomics and liquid biopsy)and standardized platforms to bridge computational pathology and precision oncology,ultimately improving personalized therapeutic strategies for liver malignancies.This synthesis aims to guide research translation and advance personalized therapeutic strategies for liver malignancies.
基金Supported by National High Level Hospital Clinical Research Funding,No.BJ-2022-145China Endocrinology and Metabolism Young Scientific Talent Research Project,No.2021-N-03.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM),driven by insulin resistance and β cell dysfunction,necessitates reliable assessment of β cell function.C-peptide(CP)measurement,a stable marker of endogenous insulin secretion,is useful for this clinically as it avoids interference from exogenous insulin.While fasting CP(FCP)and postprandial CP(PCP),along with glucose-adjusted indices and ratios,such as FCP/fasting plasma glucose(FPG),2 hours postprandial CP(2hCP)/postprandial blood glucose(PBG)and CP ratio,are used,their comparative efficacy in reflectingβcell function remains unclear.Hemoglobin A1c(HbA1c),a key glycemic control indicator,theoretically linksβcell function to complications,but limited studies have explored the associations between diverse CP indices,HbA1c,and diabetic microvascular complications.AIM To investigate the relationships between different CP indices and HbA1c as well as diabetic microvascular complications in T2DM.METHODS T2DM patients admitted to Department of Endocrinology at Beijing Hospital between July 1,2021 and December 31,2021 were included in the study.Clinical and laboratory data were collected,including CP levels,glucose levels,HbA1c levels and diabetic microvascular complications.Statistical analysis was performed using Statistical Package for the Social Sciences 24.0.RESULTS A total of 453 patients were included in the final analysis.Adjusted by confounding factors,CP ratio and CP/blood glucose(BG)ratio were not relevant to HbA1c,but FCP,2hCP,delta CP,FCP/FPG,2hCP/PBG and delta CP/BG were still negatively correlated to HbA1c,of which 2hCP/PBG showed the strongest negative correlation(r=-0.485,P<0.001).Independent of HbA1c and other confounding factors,2hCP,2hCP/PBG,delta CP and delta CP/BG were protective factors of diabetic retinopathy while 2hCP,delta CP and FCP/FPG were protective factors of diabetic peripheral neuropathy.CONCLUSION This study indicates that higher levels of CP indices suggest better glucose control and a lower prevalence of diabetic microvascular complications,and PCP indices,particularly 2hCP/PBG,were more relevant to HbA1c and diabetic microvascular complications than FCP indices.These results suggest CP-related indices could be useful biomarkers for diabetes management,warranting further research.
