Atrial septal aneurysm(ASA)is defined as excursion of the atrial septum exceeding 10 mm beyond the atrial septum into the right or left atrium,or a combined total excursion of 15 mm on the right and left sides during ...Atrial septal aneurysm(ASA)is defined as excursion of the atrial septum exceeding 10 mm beyond the atrial septum into the right or left atrium,or a combined total excursion of 15 mm on the right and left sides during the cardiac cycle.According to previous studies,20–40%of patent foramen ovale(PFO)cases are accompanied by ASAs.ASA is associated with the presence of PFO,left atrial dysfunction,cryptogenic stroke,migraine,and arterial embolism,thus making closure of PFO in patients with concomitant ASA necessary but challenging.The anatomy of ASAs associated with PFO has crucial effects on complications after the closure procedure;therefore,several factors must be considered.Herein,we review the clinical implications of concomitant PFO and ASA;discuss the complications occurring after the closure procedure;and provide practical guidance for the closure of concomitant PFO and ASA.展开更多
Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects ...Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.展开更多
Aortic stenosis （AS） is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a prior...Aortic stenosis （AS） is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a priority. In elderly patients, AS usually involves trileaflet valves and is referred to as degenerative calcific processes. Scientific evidence suggests the involvement of an active ＂atherosclerosis-like＂ pathogenesis in the initiation phase of degenerative AS. To the contrary, the progression could be driven by different forces （such as mechanical stress, genetic factors and interaction between inflammation and calcification）. The improved understanding presents potentially new therapeutic targets for preventing and inhibiting the development and progression of the disease. Furthermore, in clinical practice the management of AS patients implies the evaluation of generalized atherosclerotic manifestations （i.e., in the coronary and carotid arteries） even for prognostic reasons. In counselling elderly patients, the risk stratification should address individual frailty beyond the generic risk scores. In these regard, the co-morbidities, and in particular those linked to the global atherosclerotic burden, should be carefully investigated in order to define the risk/benefit ratio for invasive treatment strategies. We present a detailed overview of insights in pathogenesis of AS with possible practical implications.展开更多
Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Becaus...Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.展开更多
Over past decades,takotsubo cardiomyopathy(TTC)has drawn a substantial interest as a unique form of acute and reversible cardiomyopathy that usually emerges in response to adrenergic hyperactivation associated with a ...Over past decades,takotsubo cardiomyopathy(TTC)has drawn a substantial interest as a unique form of acute and reversible cardiomyopathy that usually emerges in response to adrenergic hyperactivation associated with a variety of emotional and physical triggers.[1,2]Even though,this phenomenon is generally characterized by an apical balloning pattern(classical variant),it might occasionally present with atypical morphological variants including mid-ventricular,inverted and focal forms of myocardial involvement.展开更多
BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expres...BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.展开更多
Background Recently,computational fluid dynamics(CFD)has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis(sICAS)and investigate the clinical implications of its haemodynamic featur...Background Recently,computational fluid dynamics(CFD)has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis(sICAS)and investigate the clinical implications of its haemodynamic features,which were systematically reviewed in this study.Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements,we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.Results 19 articles met the inclusion criteria,all studies recruiting patients from China.Most studies used CT angiography(CTA)as the source image for vessel segmentation,and generic boundary conditions,rigid vessel wall and Newtonian fluid assumptions for CFD modelling,in patients with 50%-99%sICAS.Pressure and wall shear stress(WSS)were quantified in almost all studies,and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio(PR)and stenotic-throat to prestenotic WSS ratio(WSSR).Lower PR was associated with more severe stenosis,better leptomeningeal collaterals,prolonged perfusion time and internal borderzone infarcts.Higher WSSR and other WSS measures were associated with positive vessel wall remodelling,regression of luminal stenosis and artery-to artery embolism.Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease.Moreover,translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy,which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.Conclusions CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS.Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS,for its wider applications in clinical research and practice.展开更多
Alzheimer’s disease(AD)is the leading cause of dementia and its incidence continues to increase,thereby placing a heavy burden on caregivers as well as society in general.The primary pathological features of AD inclu...Alzheimer’s disease(AD)is the leading cause of dementia and its incidence continues to increase,thereby placing a heavy burden on caregivers as well as society in general.The primary pathological features of AD include extracellular amyloid-beta(Aβ)plaques and intracellular neurofibrillary tangles(NFTs),as well as synaptic and neuronal loss,activated microglia,and reactive astrocytes.[1]These pathological changes generally progress from an asymptomatic phase to clinically detectable cognitive impairment,and this process typically occurs over several years.展开更多
This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabe...This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabetic retinopathy and explored novel treatment modalities.This editorial highlights the importance of these advancements and emphasizes the need for continued research and innovation for the enhanced management of diabetic retinopathy.It also reflects upon the implications of the authors’review findings for clinical practice and future research directions,underscoring the potential of emerging therapies for improving patient outcomes and providing a deeper understanding of disease mechanisms.展开更多
This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various ...This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various adjunctive therapies in improving the outcomes of diabetic retinopathy and managing associated complications.Herein,we highlight the key roles of pharmacological adjuvants in optimizing surgical techniques,minimizing intraoperative challenges,and enhancing postoperative recovery.We further discuss the potential implications of this approach for clinical practice and future research directions in this evolving field.Overall,this editorial underscores the importance of incorporating pharmacological adjuvants into standard diabetic vitrectomy care to improve surgical outcomes and thus patients’quality of life.展开更多
Per-and polyfluoroalkyl substances(PFAS)are a diverse group of synthetic chemicals.Their nu-merous applications in industrial manufacturing and consumer products have resulted in widespread human exposure.Known as“fo...Per-and polyfluoroalkyl substances(PFAS)are a diverse group of synthetic chemicals.Their nu-merous applications in industrial manufacturing and consumer products have resulted in widespread human exposure.Known as“forever chemicals”due to their persistence in the environment,PFAs have been linked to adverse health effects,including increased risks of certain cancers,reduced antibody responses to vaccines,and elevated cholesterol levels,as noted in literature reviews by the us Environmental Protection Agency(EPA).展开更多
BACKGROUND Lumbar disc extrusion,a common spinal disorder,is particularly uncommon in its severely displaced form,especially in young patients.This condition can pose diagnostic challenges due to its nonspecific prese...BACKGROUND Lumbar disc extrusion,a common spinal disorder,is particularly uncommon in its severely displaced form,especially in young patients.This condition can pose diagnostic challenges due to its nonspecific presentation.CASE SUMMARY A 36-year-old male patient presented with persistent low back pain and radiating leg pain lasting half a month,which had worsened over the previous four days.Lumbar magnetic resonance imaging scans showed an abnormal signal within the vertebral canal at the L3 level,suggesting either a disc cyst or an epidural hematoma.Based on these findings,the patient was provisionally diagnosed with either condition.Surgical exploration was conducted,revealing an extruded lumbar disc,which was subsequently excised.Following surgery,the patient's symptoms completely resolved.CONCLUSION High-grade lumbar disc extrusion in young patients is rare but should be considered in sedentary,physically inactive individuals presenting with lumbocrural pain and abnormal magnetic resonance imaging findings.Early and accurate diagnosis is crucial to avoid misdiagnosis,and prompt open surgery may be necessary in severe cases to alleviate symptoms.The case highlights the impotance of a thorough diagnostic workup and timely surgical intervention in managing such rare but potentially severe spinal disorders.展开更多
Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on sp...Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.展开更多
Gilbert’s syndrome(GS)is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism.This review,based on peer-reviewed articles spanning f...Gilbert’s syndrome(GS)is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism.This review,based on peer-reviewed articles spanning from 1977 to January 2024 and sourced through the PubMed platform,provides an overview of current knowledge regarding GS.Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome.More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase,significantly enhancing our understanding of the pathogenesis of GS.Recent studies have also investigated clinical implications of GS,including its association with metabolic associated steatotic liver disease,cardiovascular disease,mental health and mortality risk,highlighting the complex interplay between genetic factors,bilirubin metabolism,and clinical outcomes.展开更多
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease i...Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.展开更多
Ephrin-A1 is a protein that in humans is encoded by the EFNA1 gene.The ephrins and EPH-related receptors comprise the largest subfamily of receptor proteintyrosine kinases which play an indispensable role in normal gr...Ephrin-A1 is a protein that in humans is encoded by the EFNA1 gene.The ephrins and EPH-related receptors comprise the largest subfamily of receptor proteintyrosine kinases which play an indispensable role in normal growth and development or in the pathophysiology of various tumors.The role of EFNA1 in tumorigenesis and development is complex and depends on the cell type and microenvironment which in turn affect the expression of EFNA1.This article reviews the expression,prognostic value,regulation and clinical significance of EFNA1 in gastrointestinal tumors.展开更多
Harringtonine(H) level in serum was quantified by high-performance liquid chromatographic (HPLC) technique and its pharmacokinetic parameters were determined in 11 patients with ANLL after 4 hours continuous infusion ...Harringtonine(H) level in serum was quantified by high-performance liquid chromatographic (HPLC) technique and its pharmacokinetic parameters were determined in 11 patients with ANLL after 4 hours continuous infusion of 4 mg of H. 74 serum samples over the range of H administered 1-6 mg/d were also determined, the dose of H administered paralleled the mean serum H concentration, but the highest concentration were 1.6-7 folds higher than the lowest under the same doses. It seems that the dosage of harringtonine must be individualized in order to achieve better antileukemia effect. It was found that under the similar serum H concentration the marrow blast decrease index (MBDI) in types M4 and M5 of ANLL is much more greater than in M2 after the first course of chemotherapy and in 3 patients of M2, the serum H level and the MBDI show positive correlation.展开更多
Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of Califor...Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.展开更多
Salivary gland stem/progenitor cells(SSPCs)hold signifcant potential for regenerative medicine,especially for patients sufering from salivary gland dysfunction due to various causes such as radiation therapy,Sjög...Salivary gland stem/progenitor cells(SSPCs)hold signifcant potential for regenerative medicine,especially for patients sufering from salivary gland dysfunction due to various causes such as radiation therapy,Sjögren’s syn-drome,and aging.This review provides a comprehensive overview of SSPCs,including their characteristics,isolation,culture techniques,diferentiation pathways,and their role in tissue regeneration.Additionally,we highlight recent advances in cell-and tissue-based therapies,such as SSPC transplantation and bioengineered organ replacements.The challenges in translating SSPC research into efective clinical therapies are also discussed,alongside proposed solutions and future research directions.展开更多
Purpose:To conduct a review to systematically evaluate the use of anterior segment optical coherence tomography(AS-OCT)in measuring anterior scleral thickness across diverse ocular conditions and its clinical implicat...Purpose:To conduct a review to systematically evaluate the use of anterior segment optical coherence tomography(AS-OCT)in measuring anterior scleral thickness across diverse ocular conditions and its clinical implications.Methods:Literature search was conducted across electronic databases,including PubMed,Scopus,and Embase,to identify relevant studies.The risk of bias was assessed,and the main characteristics of each studies were analyzed.We calculated the overall mean anterior scleral thickness using the data which have measurement at the same locations.Results:A total of 32 studies were included that utilized AS-OCT to measure anterior scleral thickness in both healthy subjects and individuals with ocular disorders such as myopia,keratoconus,scleritis,and others.The review found that anterior scleral thickness is significantly influenced by age,diurnal variation,and specific ocular conditions.For example,myopic eyes may exhibit thinner sclera,particularly along certain meridians,while conditions like scleritis showed increased scleral thickness due to inflammation.However,some studies have inconsistent results.Additionally,AS-OCT proved effective in detecting subtle variations in anterior scleral thickness,which could be linked to the progression of ocular diseases.Conclusions:Anterior scleral thickness varies considerably depending on age,time of day,and ocular health,making it a valuable parameter in the assessment of eye conditions.AS-OCT's ability to measure these variations non-invasively broadens its application in both clinical practice and research,offering new insights into the biomechanical properties of the sclera and their implications for ocular diseases.展开更多
文摘Atrial septal aneurysm(ASA)is defined as excursion of the atrial septum exceeding 10 mm beyond the atrial septum into the right or left atrium,or a combined total excursion of 15 mm on the right and left sides during the cardiac cycle.According to previous studies,20–40%of patent foramen ovale(PFO)cases are accompanied by ASAs.ASA is associated with the presence of PFO,left atrial dysfunction,cryptogenic stroke,migraine,and arterial embolism,thus making closure of PFO in patients with concomitant ASA necessary but challenging.The anatomy of ASAs associated with PFO has crucial effects on complications after the closure procedure;therefore,several factors must be considered.Herein,we review the clinical implications of concomitant PFO and ASA;discuss the complications occurring after the closure procedure;and provide practical guidance for the closure of concomitant PFO and ASA.
文摘Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.
文摘Aortic stenosis （AS） is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a priority. In elderly patients, AS usually involves trileaflet valves and is referred to as degenerative calcific processes. Scientific evidence suggests the involvement of an active ＂atherosclerosis-like＂ pathogenesis in the initiation phase of degenerative AS. To the contrary, the progression could be driven by different forces （such as mechanical stress, genetic factors and interaction between inflammation and calcification）. The improved understanding presents potentially new therapeutic targets for preventing and inhibiting the development and progression of the disease. Furthermore, in clinical practice the management of AS patients implies the evaluation of generalized atherosclerotic manifestations （i.e., in the coronary and carotid arteries） even for prognostic reasons. In counselling elderly patients, the risk stratification should address individual frailty beyond the generic risk scores. In these regard, the co-morbidities, and in particular those linked to the global atherosclerotic burden, should be carefully investigated in order to define the risk/benefit ratio for invasive treatment strategies. We present a detailed overview of insights in pathogenesis of AS with possible practical implications.
文摘Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.
文摘Over past decades,takotsubo cardiomyopathy(TTC)has drawn a substantial interest as a unique form of acute and reversible cardiomyopathy that usually emerges in response to adrenergic hyperactivation associated with a variety of emotional and physical triggers.[1,2]Even though,this phenomenon is generally characterized by an apical balloning pattern(classical variant),it might occasionally present with atypical morphological variants including mid-ventricular,inverted and focal forms of myocardial involvement.
文摘BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.
基金supported by General Research Fund(Ref No.14106019)Early Career Scheme(Ref No.24103122)+3 种基金Research Grants Council of Hong KongHealth and Medical Research Fund(Reference No.10210366)Hong Kong Food and Health Bureauand Li Ka Shing Institute of Health Sciences.
文摘Background Recently,computational fluid dynamics(CFD)has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis(sICAS)and investigate the clinical implications of its haemodynamic features,which were systematically reviewed in this study.Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements,we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.Results 19 articles met the inclusion criteria,all studies recruiting patients from China.Most studies used CT angiography(CTA)as the source image for vessel segmentation,and generic boundary conditions,rigid vessel wall and Newtonian fluid assumptions for CFD modelling,in patients with 50%-99%sICAS.Pressure and wall shear stress(WSS)were quantified in almost all studies,and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio(PR)and stenotic-throat to prestenotic WSS ratio(WSSR).Lower PR was associated with more severe stenosis,better leptomeningeal collaterals,prolonged perfusion time and internal borderzone infarcts.Higher WSSR and other WSS measures were associated with positive vessel wall remodelling,regression of luminal stenosis and artery-to artery embolism.Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease.Moreover,translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy,which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.Conclusions CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS.Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS,for its wider applications in clinical research and practice.
基金supported by grants from the Science and Technology Innovation 2030 Major Projects(No.2022ZD0211600)the Shanghai Municipal Health Commission Emerging Interdisciplinary Research Project(No.2022JC014).
文摘Alzheimer’s disease(AD)is the leading cause of dementia and its incidence continues to increase,thereby placing a heavy burden on caregivers as well as society in general.The primary pathological features of AD include extracellular amyloid-beta(Aβ)plaques and intracellular neurofibrillary tangles(NFTs),as well as synaptic and neuronal loss,activated microglia,and reactive astrocytes.[1]These pathological changes generally progress from an asymptomatic phase to clinically detectable cognitive impairment,and this process typically occurs over several years.
文摘This editorial discusses recent advancements and ongoing challenges in diabetic retinopathy,as reviewed by Morya et al in their comprehensive analysis.In their review,Morya et al discussed the pathophysiology of diabetic retinopathy and explored novel treatment modalities.This editorial highlights the importance of these advancements and emphasizes the need for continued research and innovation for the enhanced management of diabetic retinopathy.It also reflects upon the implications of the authors’review findings for clinical practice and future research directions,underscoring the potential of emerging therapies for improving patient outcomes and providing a deeper understanding of disease mechanisms.
文摘This editorial offers insights from a minireview by Venkatesh et al,who explored pharmacological adjuvants for diabetic vitrectomy.Specifically,they synthesized current knowledge and evaluated the efficacy of various adjunctive therapies in improving the outcomes of diabetic retinopathy and managing associated complications.Herein,we highlight the key roles of pharmacological adjuvants in optimizing surgical techniques,minimizing intraoperative challenges,and enhancing postoperative recovery.We further discuss the potential implications of this approach for clinical practice and future research directions in this evolving field.Overall,this editorial underscores the importance of incorporating pharmacological adjuvants into standard diabetic vitrectomy care to improve surgical outcomes and thus patients’quality of life.
基金supported by the National Natural Science Foundation of China(42222710).
文摘Per-and polyfluoroalkyl substances(PFAS)are a diverse group of synthetic chemicals.Their nu-merous applications in industrial manufacturing and consumer products have resulted in widespread human exposure.Known as“forever chemicals”due to their persistence in the environment,PFAs have been linked to adverse health effects,including increased risks of certain cancers,reduced antibody responses to vaccines,and elevated cholesterol levels,as noted in literature reviews by the us Environmental Protection Agency(EPA).
文摘BACKGROUND Lumbar disc extrusion,a common spinal disorder,is particularly uncommon in its severely displaced form,especially in young patients.This condition can pose diagnostic challenges due to its nonspecific presentation.CASE SUMMARY A 36-year-old male patient presented with persistent low back pain and radiating leg pain lasting half a month,which had worsened over the previous four days.Lumbar magnetic resonance imaging scans showed an abnormal signal within the vertebral canal at the L3 level,suggesting either a disc cyst or an epidural hematoma.Based on these findings,the patient was provisionally diagnosed with either condition.Surgical exploration was conducted,revealing an extruded lumbar disc,which was subsequently excised.Following surgery,the patient's symptoms completely resolved.CONCLUSION High-grade lumbar disc extrusion in young patients is rare but should be considered in sedentary,physically inactive individuals presenting with lumbocrural pain and abnormal magnetic resonance imaging findings.Early and accurate diagnosis is crucial to avoid misdiagnosis,and prompt open surgery may be necessary in severe cases to alleviate symptoms.The case highlights the impotance of a thorough diagnostic workup and timely surgical intervention in managing such rare but potentially severe spinal disorders.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,No.32070726,and No.82370715National Key R&D Program of China,No.2023YFC2507904the Innovation Group Project of Hubei Province,No.2023AFA026.
文摘Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.
文摘Gilbert’s syndrome(GS)is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism.This review,based on peer-reviewed articles spanning from 1977 to January 2024 and sourced through the PubMed platform,provides an overview of current knowledge regarding GS.Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome.More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase,significantly enhancing our understanding of the pathogenesis of GS.Recent studies have also investigated clinical implications of GS,including its association with metabolic associated steatotic liver disease,cardiovascular disease,mental health and mortality risk,highlighting the complex interplay between genetic factors,bilirubin metabolism,and clinical outcomes.
基金supported by the National Research Foundation of South Korea(2023R1A2C2004516,RS-2023-00219399 to SPY,and 2022R1I1A1A01063513 to MGJ)。
文摘Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.
基金Supported by the Natural Science Foundation of China,No.81972801the Guangdong Basic and Applied Basic Research Foundation,No.2019A1515011873+1 种基金the Medical Project of Science and Technology Planning of Shantou,No.200605115266724the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG01B.
文摘Ephrin-A1 is a protein that in humans is encoded by the EFNA1 gene.The ephrins and EPH-related receptors comprise the largest subfamily of receptor proteintyrosine kinases which play an indispensable role in normal growth and development or in the pathophysiology of various tumors.The role of EFNA1 in tumorigenesis and development is complex and depends on the cell type and microenvironment which in turn affect the expression of EFNA1.This article reviews the expression,prognostic value,regulation and clinical significance of EFNA1 in gastrointestinal tumors.
文摘Harringtonine(H) level in serum was quantified by high-performance liquid chromatographic (HPLC) technique and its pharmacokinetic parameters were determined in 11 patients with ANLL after 4 hours continuous infusion of 4 mg of H. 74 serum samples over the range of H administered 1-6 mg/d were also determined, the dose of H administered paralleled the mean serum H concentration, but the highest concentration were 1.6-7 folds higher than the lowest under the same doses. It seems that the dosage of harringtonine must be individualized in order to achieve better antileukemia effect. It was found that under the similar serum H concentration the marrow blast decrease index (MBDI) in types M4 and M5 of ANLL is much more greater than in M2 after the first course of chemotherapy and in 3 patients of M2, the serum H level and the MBDI show positive correlation.
基金supported by a grant from the Nantong City Science and Technology Bureau Project(no.:HS2020005).
文摘Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.
文摘Salivary gland stem/progenitor cells(SSPCs)hold signifcant potential for regenerative medicine,especially for patients sufering from salivary gland dysfunction due to various causes such as radiation therapy,Sjögren’s syn-drome,and aging.This review provides a comprehensive overview of SSPCs,including their characteristics,isolation,culture techniques,diferentiation pathways,and their role in tissue regeneration.Additionally,we highlight recent advances in cell-and tissue-based therapies,such as SSPC transplantation and bioengineered organ replacements.The challenges in translating SSPC research into efective clinical therapies are also discussed,alongside proposed solutions and future research directions.
基金supported by the National Postdoctoral Researcher Funding Program,National Natural Science Foundation of China(82271112).
文摘Purpose:To conduct a review to systematically evaluate the use of anterior segment optical coherence tomography(AS-OCT)in measuring anterior scleral thickness across diverse ocular conditions and its clinical implications.Methods:Literature search was conducted across electronic databases,including PubMed,Scopus,and Embase,to identify relevant studies.The risk of bias was assessed,and the main characteristics of each studies were analyzed.We calculated the overall mean anterior scleral thickness using the data which have measurement at the same locations.Results:A total of 32 studies were included that utilized AS-OCT to measure anterior scleral thickness in both healthy subjects and individuals with ocular disorders such as myopia,keratoconus,scleritis,and others.The review found that anterior scleral thickness is significantly influenced by age,diurnal variation,and specific ocular conditions.For example,myopic eyes may exhibit thinner sclera,particularly along certain meridians,while conditions like scleritis showed increased scleral thickness due to inflammation.However,some studies have inconsistent results.Additionally,AS-OCT proved effective in detecting subtle variations in anterior scleral thickness,which could be linked to the progression of ocular diseases.Conclusions:Anterior scleral thickness varies considerably depending on age,time of day,and ocular health,making it a valuable parameter in the assessment of eye conditions.AS-OCT's ability to measure these variations non-invasively broadens its application in both clinical practice and research,offering new insights into the biomechanical properties of the sclera and their implications for ocular diseases.
