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
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
Diabetes is a major public health concern worldwide. Low and middle-income countries are the most affected. Diabetes self-management can significantly reduce the burden of diabetes complications and mortality. This cr...Diabetes is a major public health concern worldwide. Low and middle-income countries are the most affected. Diabetes self-management can significantly reduce the burden of diabetes complications and mortality. This cross-sectional study was conducted at the outpatient department of a county referral hospital in Kenya, from 1st August 2022 to 30th October 2022. Patients with known type II diabetes of age ≥ 20 years visiting the hospital for routine follow-up visits were included. A 7-tem Summary of Diabetes Self-care Activities (SDSAC) Questionnaire was used to assess Diabetes self-care activities. For data entry and statistical analysis, SPSS for Windows version 27.0 was used. There were 96 (39.2%) males and 149 (60.8%) females. Most of the participants were more than 61 years, 148 (60.4%). Significant association was found between the sum scale scores of dietary activities, blood glucose testing, physical activity, foot care, and neuropathy at 95% CI and (p Conclusions: Diabetes self-management activities have an impact on microvascular complications in patients with diabetes.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
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
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
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
Coronary microvascular disease(CMD)is one of the commonest causes of cardiac chest pain.The condition is more prevalent in women,and incidence is known to increase with age,hypertension,and diabetes.The pathophysiolog...Coronary microvascular disease(CMD)is one of the commonest causes of cardiac chest pain.The condition is more prevalent in women,and incidence is known to increase with age,hypertension,and diabetes.The pathophysiological pathways are heterogenous and related to intrinsic vascular and endothelial dysfunction.Furthermore,this entity is known to be associated with adverse cardiovascular outcomes.Despite this,there is inertia amongst cardiologists to further evaluate patients with non-critical coronary artery disease and suspected CMD.With refinement in technology,we have now better understanding of CMD and invasive testing in the catheterization laboratory is a viable option for confirming the diagnosis of CMD.However,despite advances in diagnosing and stratifying this entity,therapeutic options remain limited and poorly defined.In this editorial,we will briefly focus on the pathophysiology and invasive assessment and therapeutic options available for CMD.展开更多
The blood-brain barrier(BBB)keeps poisons and infections out of the brain.Some viruses can pass through this barrier and replicate in the central nervous system(CNS).Velogenic Newcastle disease virus(VNDV)is a neurotr...The blood-brain barrier(BBB)keeps poisons and infections out of the brain.Some viruses can pass through this barrier and replicate in the central nervous system(CNS).Velogenic Newcastle disease virus(VNDV)is a neurotropic virus that causes avian nonsuppurative encephalitis.VNDV often develops into a chronic infection that seriously affects poultry health in partially immune birds.The routes by which the virus enters the chicken brain are poorly understood.In this study,we discovered that VNDV increased BBB permeability in vivo and in vitro by breaking the tight junction protein zona occludens-1(ZO-1)continuity of chicken brain microvascular endothelial cells(chBMECs).By investigating the susceptibility of chBMECs to NDV infection,we found that VNDV but not lentogenic NDV was detected in the basolateral compartment in transwell assays after apical infection,suggesting that efficient replication and transcellular transport of the virus across the BBB in vitro.Furthermore,viral replication and BBB permeability were reduced during the early stage of infection by using the dynamin inhibitor dynasore.Our data demonstrate that VNDV invades the chicken brain by infecting and damaging the tight junction of chBMECs directly to increase BBB permeability.VNDV could infect chBMECs via endocytosis.As a result,our findings provide compelling evidence for VNDV entrance into the brain via the BBB,paving the way for the development of medications for NDV prevention and therapy.展开更多
Objective:Evidence pertaining to the associations between hyperuricemia and diabetic microvascular complications is limited and inconclusive.In this study,we aimed to prospectively investigate the independent associat...Objective:Evidence pertaining to the associations between hyperuricemia and diabetic microvascular complications is limited and inconclusive.In this study,we aimed to prospectively investigate the independent associations of hyperuricemia and retinopathy,nephropathy and neuropathy in individuals with type 2 diabetes mellitus(T2DM).Methods:This cohort study enrolled 25,094 participants from UK Biobank with T2DM and without microvascular complications at baseline.Hyperuricemia was defined as serum uric acid(SUA)higher than 420μmol/L.The incidence of diabetic microvascular complications was identified from hospital inpatient records that were coded according to the International Classification of Diseases(ICD)-10 coding system.Multivariable adjusted Cox proportional hazards regression models were used to calculate adjusted hazard ratios(aHR).Results:Among all participants,3,844(15.3%)were classified as having hyperuricemia at baseline.During a median follow-up of 14.0 years,555(14.4%)individuals with hyperuricemia developed diabetic microvascular complications,compared with 12.6%of individuals without hyperuricemia(P=0.002).In the multivariable-adjusted model accounted for socioeconomic status,lifestyle factors,physical and biochemical measurements,and medication use,when compared with individuals of T2DM who had a normal SUA level,those with hyperuricemia had an 82.9%higher risk of developing diabetic nephropathy(95%CI:1.41-2.38,P<0.001),and a 30.2%higher risk of diabetic neuropathy(95%CI:1.06-1.60,P=0.011).However,the association between hyperuricemia and diabetic retinopathy was not statistically significant(aHR:1.070,95%CI:0.94-1.22,P=0.320).Conclusions:Hyperuricemia was independently associated with diabetic nephropathy and neuropathy but not retinopathy in individuals with T2DM.These findings underscore the importance of monitoring SUA level in prevention of certain microvascular complications.展开更多
AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRN...AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRNA)-mediated interference was conducted to knockdown nuclear factor erythroid 2-related factor 2(Nrf2).Using reverse transcription-polymerase chain reaction(RT-PCR),the expression level of Nrf2 was determined from human retinal microvascular endothelial cells(HRMECs)transfected with either si-NC or si-Nrf2.After that,cells were treated with 10 nmol/L ghrelin and then cultured in a high glucose(30 mmol/L)environment.EdU assay was utilized to assess cell proliferation,while transmission electron microscopy was employed to observe mitochondrial morphology.Flow cytometry was used to measure the level of intracellular reactive oxygen species(ROS),and biochemical assays were conducted to detect malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and ferrous iron(Fe2+).Western blotting was used to identify the presence of ferroptosis-related proteins such as glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and haem oxygenase-1(HO-1).RESULTS:Under a high glucose environment,ghrelin could significantly promote the proliferation of HRMECs and mitochondrial status,remarkably decrease the levels of intracellular ROS and MDA,and up-regulate the level of GSH and SOD.Besides,ghrelin greatly reduced Fe2+level in the cells while increased protein levels of GPX4 and SLC7A11.Subsequently,we found that high glucose induced inactivation of Nrf2/HO-1 axis and the protein expression profile were significantly promoted by ghrelin.Moreover,silencing of Nrf2 by siRNA delivery markedly diminished the changes induced by ghrelin in high glucose-induced HRMECs,shown as reduced cell proliferation and increased mitochondrial malformation,up-regulated ROS,MDA,Fe^(2+),GPX4 and SLC7A11,as well as down-regulated GSH,SOD,Nrf2 and HO-1.CONCLUSION:Ghrelin attenuates high glucose-induced injury of retinal endothelial cells via inhibiting ferroptosis,and activation of Nrf2/HO-1 pathway may be one of the mechanisms involved in this effect of ghrelin.展开更多
Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial...Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.展开更多
BACKGROUND Microvascular invasion(MVI)is a significant indicator of the aggressive behavior of hepatocellular carcinoma(HCC).Expanding the surgical resection margin and performing anatomical liver resection may improv...BACKGROUND Microvascular invasion(MVI)is a significant indicator of the aggressive behavior of hepatocellular carcinoma(HCC).Expanding the surgical resection margin and performing anatomical liver resection may improve outcomes in patients with MVI.However,no reliable preoperative method currently exists to predict MVI status or to identify patients at high-risk group(M2).AIM To develop and validate models based on contrast-enhanced computed tomo-graphy(CECT)radiomics and clinicoradiological factors to predict MVI and identify M2 among patients with hepatitis B virus-related HCC(HBV-HCC).The ultimate goal of the study was to guide surgical decision-making.METHODS A total of 270 patients who underwent surgical resection were retrospectively analyzed.The cohort was divided into a training dataset(189 patients)and a validation dataset(81)with a 7:3 ratio.Radiomics features were selected using intra-class correlation coefficient analysis,Pearson or Spearman’s correlation analysis,and the least absolute shrinkage and selection operator algorithm,leading to the construction of radscores from CECT images.Univariate and multivariate analyses identified significant clinicoradiological factors and radscores associated with MVI and M2,which were subsequently incorporated into predictive models.The models’performance was evaluated using calibration,discrimination,and clinical utility analysis.RESULTS Independent risk factors for MVI included non-smooth tumor margins,absence of a peritumoral hypointensity ring,and a high radscore based on delayed-phase CECT images.The MVI prediction model incorporating these factors achieved an area under the curve(AUC)of 0.841 in the training dataset and 0.768 in the validation dataset.The M2 prediction model,which integrated the radscore from the 5 mm peritumoral area in the CECT arterial phase,α-fetoprotein level,enhancing capsule,and aspartate aminotransferase level achieved an AUC of 0.865 in the training dataset and 0.798 in the validation dataset.Calibration and decision curve analyses confirmed the models’good fit and clinical utility.CONCLUSION Multivariable models were constructed by combining clinicoradiological risk factors and radscores to preoper-atively predict MVI and identify M2 among patients with HBV-HCC.Further studies are needed to evaluate the practical application of these models in clinical settings.展开更多
Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component de...Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.展开更多
While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a p...While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.展开更多
BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the ...BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.展开更多
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Diabetes is a major public health concern worldwide. Low and middle-income countries are the most affected. Diabetes self-management can significantly reduce the burden of diabetes complications and mortality. This cross-sectional study was conducted at the outpatient department of a county referral hospital in Kenya, from 1st August 2022 to 30th October 2022. Patients with known type II diabetes of age ≥ 20 years visiting the hospital for routine follow-up visits were included. A 7-tem Summary of Diabetes Self-care Activities (SDSAC) Questionnaire was used to assess Diabetes self-care activities. For data entry and statistical analysis, SPSS for Windows version 27.0 was used. There were 96 (39.2%) males and 149 (60.8%) females. Most of the participants were more than 61 years, 148 (60.4%). Significant association was found between the sum scale scores of dietary activities, blood glucose testing, physical activity, foot care, and neuropathy at 95% CI and (p Conclusions: Diabetes self-management activities have an impact on microvascular complications in patients with diabetes.
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 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 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.
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.
文摘Coronary microvascular disease(CMD)is one of the commonest causes of cardiac chest pain.The condition is more prevalent in women,and incidence is known to increase with age,hypertension,and diabetes.The pathophysiological pathways are heterogenous and related to intrinsic vascular and endothelial dysfunction.Furthermore,this entity is known to be associated with adverse cardiovascular outcomes.Despite this,there is inertia amongst cardiologists to further evaluate patients with non-critical coronary artery disease and suspected CMD.With refinement in technology,we have now better understanding of CMD and invasive testing in the catheterization laboratory is a viable option for confirming the diagnosis of CMD.However,despite advances in diagnosing and stratifying this entity,therapeutic options remain limited and poorly defined.In this editorial,we will briefly focus on the pathophysiology and invasive assessment and therapeutic options available for CMD.
基金supported by the National Natural Science Foundation of China(32302864 and 31572533)the Shandong Provincial Natural Science Foundation,China(ZR2021QC185)the Agricultural Science and Technology Innovation Project of Shandong Academy of Agricultural Sciences,China(CXGC2023F11)。
文摘The blood-brain barrier(BBB)keeps poisons and infections out of the brain.Some viruses can pass through this barrier and replicate in the central nervous system(CNS).Velogenic Newcastle disease virus(VNDV)is a neurotropic virus that causes avian nonsuppurative encephalitis.VNDV often develops into a chronic infection that seriously affects poultry health in partially immune birds.The routes by which the virus enters the chicken brain are poorly understood.In this study,we discovered that VNDV increased BBB permeability in vivo and in vitro by breaking the tight junction protein zona occludens-1(ZO-1)continuity of chicken brain microvascular endothelial cells(chBMECs).By investigating the susceptibility of chBMECs to NDV infection,we found that VNDV but not lentogenic NDV was detected in the basolateral compartment in transwell assays after apical infection,suggesting that efficient replication and transcellular transport of the virus across the BBB in vitro.Furthermore,viral replication and BBB permeability were reduced during the early stage of infection by using the dynamin inhibitor dynasore.Our data demonstrate that VNDV invades the chicken brain by infecting and damaging the tight junction of chBMECs directly to increase BBB permeability.VNDV could infect chBMECs via endocytosis.As a result,our findings provide compelling evidence for VNDV entrance into the brain via the BBB,paving the way for the development of medications for NDV prevention and therapy.
基金supported by the Guangzhou Basic Research Program,City&University(Institute)Joint Funding Project(2023A03J0174).
文摘Objective:Evidence pertaining to the associations between hyperuricemia and diabetic microvascular complications is limited and inconclusive.In this study,we aimed to prospectively investigate the independent associations of hyperuricemia and retinopathy,nephropathy and neuropathy in individuals with type 2 diabetes mellitus(T2DM).Methods:This cohort study enrolled 25,094 participants from UK Biobank with T2DM and without microvascular complications at baseline.Hyperuricemia was defined as serum uric acid(SUA)higher than 420μmol/L.The incidence of diabetic microvascular complications was identified from hospital inpatient records that were coded according to the International Classification of Diseases(ICD)-10 coding system.Multivariable adjusted Cox proportional hazards regression models were used to calculate adjusted hazard ratios(aHR).Results:Among all participants,3,844(15.3%)were classified as having hyperuricemia at baseline.During a median follow-up of 14.0 years,555(14.4%)individuals with hyperuricemia developed diabetic microvascular complications,compared with 12.6%of individuals without hyperuricemia(P=0.002).In the multivariable-adjusted model accounted for socioeconomic status,lifestyle factors,physical and biochemical measurements,and medication use,when compared with individuals of T2DM who had a normal SUA level,those with hyperuricemia had an 82.9%higher risk of developing diabetic nephropathy(95%CI:1.41-2.38,P<0.001),and a 30.2%higher risk of diabetic neuropathy(95%CI:1.06-1.60,P=0.011).However,the association between hyperuricemia and diabetic retinopathy was not statistically significant(aHR:1.070,95%CI:0.94-1.22,P=0.320).Conclusions:Hyperuricemia was independently associated with diabetic nephropathy and neuropathy but not retinopathy in individuals with T2DM.These findings underscore the importance of monitoring SUA level in prevention of certain microvascular complications.
基金Supported by the Scientific Research Development Project of North Sichuan Medical College(No.CBY24-QDA01)Science and Technology Program of Shaanxi Province(No.2024SF-YBXM-324,No.2024SFYBXM-341).
文摘AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRNA)-mediated interference was conducted to knockdown nuclear factor erythroid 2-related factor 2(Nrf2).Using reverse transcription-polymerase chain reaction(RT-PCR),the expression level of Nrf2 was determined from human retinal microvascular endothelial cells(HRMECs)transfected with either si-NC or si-Nrf2.After that,cells were treated with 10 nmol/L ghrelin and then cultured in a high glucose(30 mmol/L)environment.EdU assay was utilized to assess cell proliferation,while transmission electron microscopy was employed to observe mitochondrial morphology.Flow cytometry was used to measure the level of intracellular reactive oxygen species(ROS),and biochemical assays were conducted to detect malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and ferrous iron(Fe2+).Western blotting was used to identify the presence of ferroptosis-related proteins such as glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and haem oxygenase-1(HO-1).RESULTS:Under a high glucose environment,ghrelin could significantly promote the proliferation of HRMECs and mitochondrial status,remarkably decrease the levels of intracellular ROS and MDA,and up-regulate the level of GSH and SOD.Besides,ghrelin greatly reduced Fe2+level in the cells while increased protein levels of GPX4 and SLC7A11.Subsequently,we found that high glucose induced inactivation of Nrf2/HO-1 axis and the protein expression profile were significantly promoted by ghrelin.Moreover,silencing of Nrf2 by siRNA delivery markedly diminished the changes induced by ghrelin in high glucose-induced HRMECs,shown as reduced cell proliferation and increased mitochondrial malformation,up-regulated ROS,MDA,Fe^(2+),GPX4 and SLC7A11,as well as down-regulated GSH,SOD,Nrf2 and HO-1.CONCLUSION:Ghrelin attenuates high glucose-induced injury of retinal endothelial cells via inhibiting ferroptosis,and activation of Nrf2/HO-1 pathway may be one of the mechanisms involved in this effect of ghrelin.
基金Program of Natural Science Foundation of Shanghai,Grant/Award Number:21ZR1453800 and 22ZR1452400Program of National Natural Science Foundation of China,Grant/Award Number:82370057+3 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Shanghai Municipal Health Commission,Grant/Award Number:20204Y0384Program of National Key Research and Development Project of China,Grant/Award Number:2023YFC2509500。
文摘Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.
基金Supported by Anhui Provincial Key Research and Development Plan,No.202104j07020048.
文摘BACKGROUND Microvascular invasion(MVI)is a significant indicator of the aggressive behavior of hepatocellular carcinoma(HCC).Expanding the surgical resection margin and performing anatomical liver resection may improve outcomes in patients with MVI.However,no reliable preoperative method currently exists to predict MVI status or to identify patients at high-risk group(M2).AIM To develop and validate models based on contrast-enhanced computed tomo-graphy(CECT)radiomics and clinicoradiological factors to predict MVI and identify M2 among patients with hepatitis B virus-related HCC(HBV-HCC).The ultimate goal of the study was to guide surgical decision-making.METHODS A total of 270 patients who underwent surgical resection were retrospectively analyzed.The cohort was divided into a training dataset(189 patients)and a validation dataset(81)with a 7:3 ratio.Radiomics features were selected using intra-class correlation coefficient analysis,Pearson or Spearman’s correlation analysis,and the least absolute shrinkage and selection operator algorithm,leading to the construction of radscores from CECT images.Univariate and multivariate analyses identified significant clinicoradiological factors and radscores associated with MVI and M2,which were subsequently incorporated into predictive models.The models’performance was evaluated using calibration,discrimination,and clinical utility analysis.RESULTS Independent risk factors for MVI included non-smooth tumor margins,absence of a peritumoral hypointensity ring,and a high radscore based on delayed-phase CECT images.The MVI prediction model incorporating these factors achieved an area under the curve(AUC)of 0.841 in the training dataset and 0.768 in the validation dataset.The M2 prediction model,which integrated the radscore from the 5 mm peritumoral area in the CECT arterial phase,α-fetoprotein level,enhancing capsule,and aspartate aminotransferase level achieved an AUC of 0.865 in the training dataset and 0.798 in the validation dataset.Calibration and decision curve analyses confirmed the models’good fit and clinical utility.CONCLUSION Multivariable models were constructed by combining clinicoradiological risk factors and radscores to preoper-atively predict MVI and identify M2 among patients with HBV-HCC.Further studies are needed to evaluate the practical application of these models in clinical settings.
基金funded by the Science and Technology Innovation Project of the China Academy of Chinese Medical Sciences(Nos.CI2021A04618 and CI2021A01401).
文摘Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.
文摘While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.
基金Supported by National Natural Science Foundation of China,No.81560278the Health Commission of Guangxi Zhuang Autonomous Region,No.Z-A20221157,No.Z20200953,and No.G201903023.
文摘BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.
