Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include...Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.展开更多
Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have...Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.展开更多
Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accoun...Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation.展开更多
The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in ...The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
Ovarian endometrioid carcinoma(OEC)accounts for~10%of epithelial ovarian cancers and displays broad morphologic diversity that complicates diagnosis and grading.Recent data show that the endometrial cancer molecular t...Ovarian endometrioid carcinoma(OEC)accounts for~10%of epithelial ovarian cancers and displays broad morphologic diversity that complicates diagnosis and grading.Recent data show that the endometrial cancer molecular taxonomy(DNA polymerase epsilon,catalytic subunit[POLE]-ultramutated,mismatch repair-deficient[MMRd],p53-abnormal,no specific molecular profile[NSMP])also applies to OEC,and that OEC is enriched for Lynch syndrome–associated tumors,supporting routine MMR testing.We aimed to synthesize contemporary evidence spanning epidemiology,histopathology and immunophenotype,diagnostic pitfalls and differential diagnosis,and to evaluate the clinical utility of The Cancer Genome Atlas(TCGA)-surrogate molecular classification for risk stratification;we also summarize implications for Lynch screening,genetic counseling,and therapeutic opportunities including immune checkpoint inhibitors and targeted approaches,with practical recommendations for diagnostic workflows.Integrating morphology with molecular classification refines diagnosis and prognostication:POLEmut/MMRd subsets generally have excellent outcomes and are candidates for de-escalation or immunotherapy,whereas p53abn/high-grade tumors carry a poorer prognosis and may warrant intensified management and trials of homologous recombination deficiency(HRD)-directed strategies;routine MMR immunohistochemistry(IHC)with reflex germline testing improves Lynch detection,and future priorities include prospective validation and multi-omics to refine NSMP and identify new targets.展开更多
A recent study by Luo et al examined the relationship between the pathological types of pancreatic cancer(PC)and their imaging characteristics.While this study presented an important step toward improving diagnostic a...A recent study by Luo et al examined the relationship between the pathological types of pancreatic cancer(PC)and their imaging characteristics.While this study presented an important step toward improving diagnostic accuracy for PC,we have several concerns regarding its generalizability,cohort selection,imaging variability,statistical methods,and potential confounding factors.We recommended that future research adopt multi-center,prospective designs to improve representation and minimize bias.Additionally,incorporating advanced imaging techniques such as radiomics and artificial intelligence and conducting more comprehensive statistical analyses would be valuable.By implementing these strategies,future studies can yield more reliable and externally validated findings that improve the clinical applicability of imaging-based differentiation of PC.Addressing these methodological issues could significantly advance the field of gastrointestinal oncology and improve patient management and outcomes.展开更多
AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening o...AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening of the GSE24673 and GSE125903 datasets,combined with GeneCards database analysis.A total of 102 RB patients and 62 traumaenucleated controls between January 2018 and December 2023 were enrolled,with their clinicopathological data and retinal tissues collected.The mRNA and methylation levels of MSH6 in retinal tissues were detected using real-time quantitative polymerase chain reaction(PCR)and methylation-specific PCR.Western blot analysis was conducted in one pair of RB and control tissues for preliminary protein-level validation of MSH6 expression.Based on the methylation status of MSH6,RB patients were categorized into two groups:low-methylation and highmethylation.Both univariate and multivariate analyses were conducted to identify independent factors influencing the methylation levels using clinicopathological data.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic potential of MSH6 methylation in RB.RESULTS:Bioinformatics analysis of public datasets revealed that MSH6 expression was downregulated across multiple cancers,RB.Consistently,in clinical RB tissues,MSH6 mRNA expression was significantly lower than that in control retinal tissues,whereas the promoter methylation level of MSH6 was markedly higher(both P<0.001),indicating that promoter hypermethylation may contribute to transcriptional silencing of MSH6 in RB.Patients with higher MSH6 methylation levels showed more advanced pathological classification and a higher frequency of metastasis.Multivariate logistic regression confirmed that metastatic status(P=0.008,OR=3.51)and pathological classification(P=0.005,OR=3.7)were independent factors associated with MSH6 methylation.Receiver operating characteristic(ROC)analysis demonstrated that MSH6 methylation could effectively distinguish RB tissues from non-tumorous controls(AUC=0.847,sensitivity=78.43%,specificity=80.65%),suggesting that MSH6 hypermethylation may serve as a potential diagnostic biomarker for RB.CONCLUSION:The methylation level of the MSH6 gene may be a key factor in RB pathogenesis.The methylation status of the MSH6 gene is closely associated with clinicopathological features and shows diagnostic potential.展开更多
Objective:To enhance the reading skills of clinical pathology residents,it is essential to establish a well-structured electronic pathology reading library.Methods:In accordance with the Resident Standardization Train...Objective:To enhance the reading skills of clinical pathology residents,it is essential to establish a well-structured electronic pathology reading library.Methods:In accordance with the Resident Standardization Training Content and Standards(2022 Edition),clinical pathology residents are required to master pathological diagnoses across 11 systems:skin,head and neck,mediastinum and respiratory,digestive,urinary and male reproductive,female reproductive and breast,lymphatic and hematopoietic,bone and soft tissue,cardiovascular,central nervous,and endocrine diseases.Senior pathologists specializing in each subspecialty selected classic pathological slides,which were systematically scanned and compiled into an electronic pathology library.Results:A questionnaire survey was conducted to gather feedback on the electronic pathology reading library.Residents generally found it to be convenient,efficient,and conducive to learning.Conclusion:Training in clinical pathology diagnosis is a core component of standardized resident training.The electronic pathology reading library has been well-received and recognized by resident doctors.However,further efforts are needed to explore diverse teaching methods that align with modern educational approaches,ultimately contributing to the development of highly skilled resident doctors.展开更多
BACKGROUND The heterogeneous group of disorders called peripheral vascular diseases(PVDs)occurs outside the heart and brain tissue to cause ischemia and severe health complications.Diagnosis accuracy is essential in s...BACKGROUND The heterogeneous group of disorders called peripheral vascular diseases(PVDs)occurs outside the heart and brain tissue to cause ischemia and severe health complications.Diagnosis accuracy is essential in starting appropriate patient management at the proper time.Modern medicine considers skin biopsies crucial diagnostic tools that yield histopathological and molecular evidence for examining PVD-related microvascular changes.AIM To evaluate skin biopsy applications in PVD diagnostics through artistic analysis of technical processes and examination of pathological and innovative molecular indicators.METHODS A systematic review of randomized controlled trials and original studies about skin biopsy utility in PVD diagnosis used PubMed,Scopus,and EMBASE search platforms.The reviewed studies met specific entry requirements,while all case reports and review articles remained excluded.RESULTS A total of 22 studies suited the research criteria that were evaluated.Researchers emphasized the value of skin biopsies for identifying inflammatory from non-inflammatory PVDs.At the same time,they detect systemic sclerosis and diabetic vasculopathy abnormalities of micro-vessels and identify endothelial dysfunction through measurements of vascular endothelial growth factor and intercellular adhesion molecule-1 and endothelial nitric oxide synthase markers.Skin biopsies require further improvement because they cause patient discomfort and produce variable diagnostic results that specialists must interpret.CONCLUSION Skin biopsies enable essential diagnostic findings about PVD and improve patient detection.The development of standardized biopsy procedures and molecular diagnosis techniques should be studied to advance PVD diagnoses in clinical practice.展开更多
Dear Editor,We aimed to describe the management of the intraoperative injury of the right external iliac artery that occurred during robot-assisted right nephroureterectomy with bladder cuff excision.Surgery was sched...Dear Editor,We aimed to describe the management of the intraoperative injury of the right external iliac artery that occurred during robot-assisted right nephroureterectomy with bladder cuff excision.Surgery was scheduled for suspected urothelial carcinoma of the distal ureter in a 60-year-old woman.The patient involved in the present research signed a dedicated form to consent to the publication of images and/or information about her.Past medical history included Brugada syndrome diagnosed in 2015,and hypercholesterolemia.Past surgical history included one cesarean section only.Family history included ovarian cancer(sister),colorectal cancer(mother),and kidney cancer(father).展开更多
One in every eight men in the US is diagnosed with prostate cancer,making it the most common cancer in men.Gleason grading is one of the most essential diagnostic and prognostic factors for planning the treatment of p...One in every eight men in the US is diagnosed with prostate cancer,making it the most common cancer in men.Gleason grading is one of the most essential diagnostic and prognostic factors for planning the treatment of prostate cancer patients.Traditionally,urological pathologists perform the grading by scoring the morphological pattern,known as the Gleason pattern,in histopathology images.However,thismanual grading is highly subjective,suffers intra-and inter-pathologist variability and lacks reproducibility.An automated grading system could be more efficient,with no subjectivity and higher accuracy and reproducibility.Automated methods presented previously failed to achieve sufficient accuracy,lacked reproducibility and depended on high-resolution images such as 40×.This paper proposes an automated Gleason grading method,ProGENET,to accurately predict the grade using low-resolution images such as 10×.This method first divides the patient’s histopathology whole slide image(WSI)into patches.Then,it detects artifacts and tissue-less regions and predicts the patch-wise grade using an ensemble network of CNN and transformer models.The proposed method adapted the International Society of Urological Pathology(ISUP)grading system and achieved 90.8%accuracy in classifying the patches into healthy and Gleason grades 1 through 5 using 10×WSI,outperforming the state-of-the-art accuracy by 27%.Finally,the patient’s grade was determined by combining the patch-wise results.The method was also demonstrated for 4−class grading and binary classification of prostate cancer,achieving 93.0%and 99.6%accuracy,respectively.The reproducibility was over 90%.Since the proposedmethod determined the grades with higher accuracy and reproducibility using low-resolution images,it is more reliable and effective than existing methods and can potentially improve subsequent therapy decisions.展开更多
Using the curriculum of horticultural plant pathology as a starting point,this paper investigates the collaborative education model of"curriculum ideology and politics+innovation and entrepreneurship".It exp...Using the curriculum of horticultural plant pathology as a starting point,this paper investigates the collaborative education model of"curriculum ideology and politics+innovation and entrepreneurship".It expounds the necessity of constructing this model,proposes implementation paths from aspects such as the integration of ideological and political elements,the cultivation of innovation and entrepreneurship capabilities,and the construction of a collaborative education mechanism.Furthermore,it analyzes the practical effects,challenges encountered,and corresponding response strategies,thereby offering a valuable reference for the training of professionals in horticulture.展开更多
AIM:To describe the alterations of the vitreous pathology and anterior chamber(AC)angle structures following transscleral cyclophotocoagulation(TSCP)and better understand the mechanism of post-laser intraocular pressu...AIM:To describe the alterations of the vitreous pathology and anterior chamber(AC)angle structures following transscleral cyclophotocoagulation(TSCP)and better understand the mechanism of post-laser intraocular pressure(IOP)reduction in angle-closure glaucoma(ACG).METHODS:Porcine eyes ex vivo and rabbit eyes in vivo were used.In porcine eyes,permeability rates of the anterior vitreous cortex(AVC)and anterior hyaloid membrane(AHM)were assessed using Schirmer’s strips.Permeability rates in the circumlental space were compared with or without TSCP bursts.Fluorescein diffusion times from the vitreous to the AC were compared between eyes with and without TSCP.In rabbit eyes,changes in IOP and AC angle structures under ultrasound biomicroscopy(UBM)were evaluated at intervals of 30min,7d,and 14d after TSCP.Vitreous pathology was examined using scanning electron microscopy(SEM)immediately and 14d after TSCP.RESULTS:In porcine eyes(n=20),the median(range)permeability rates were 10.3(range 9.8–10.8)mm/min for the AVC and 4.3(range 3.9–4.9)mm/min for the AHM(P=0.009).Permeability rates in the circumlental space were 4.2(range 3.8–4.9)mm/min in areas without TSCP,6.2(range 5.7–6.8)mm/min in areas with non-burst TSCP,and 11.3(range 10.9–11.8)mm/min in areas with burst TSCP(P=0.002).The median(range)fluorescein diffusion time was 5(range 3–8)min in eyes undergoing TSCP,whereas it was 40min(range 35–68)in eyes without TSCP(P<0.001).In rabbit eyes(n=20),SEM showed immediate localized damage to the AHM,AVC,and posterior lens zonules in areas subjected to TSCP bursts,and obvious lens zonule loss with cellular infiltration and possible vitreous liquefaction by post-op day 14.Persistent widening of AC angles was noted at postoperative days 7 and 14,although a significant reduction in IOP was only observed at postoperative day 7.CONCLUSION:TSCP-induced damage on the zonules,AHM,and AVC potentially enhances fluid outflow from the vitreous,leading to a widened AC angle and vitreous liquefaction in rabbits.These observations offer insights into mechanisms of TSCP in lowering IOP and pathogenic roles of vitreous in ACG.展开更多
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN)。
文摘Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.
基金supported by the Canadian Institutes of Health Research Project grant (PJT-169197) to QYsupported by a CGS-M fellowship from the Canadian Institutes of Health Research
文摘Alzheimer’s disease(AD)remains an incurable neurodegenerative disorder with devastating societal and personal impacts.Despite decades of intensive research,therapeutic efforts targeting the clinical stages of AD have largely failed to halt or reverse disease progression.This has prompted a critical shift in focus toward the earlier,preclinical stages of AD,where interventions may hold greater promise for altering the disease trajectory.
文摘Uveal melanoma(UM)is the most common intraocular cancer,with approximately 5.2 individuals per million affected annually in the United States.It represents approximately 3%of the global malignant melanoma cases,accounting for 80%of the overall noncutaneous melanomas.Clinically,it remains silent in about 30%of the cases;when symptomatic,it generally causes metamorphopsia(painless loss or distortion of vision)and/or photopsia(flashing or flickering of light in the visual field).Discoloration of the iris,astigmatism,glaucoma,and even blindness are other,less common clinical manifestations.Several pathophysiological mechanisms underlie the development of UM.Genetic mutations,involving especially the G protein subunit alpha q(GNAQ),guanine nucleotide-binding protein subunit alpha-11(GNA11),BRCA1 associated deubiquitinase 1(BAP1),splicing factor 3b subunit 1(SF3B1),and eukaryotic translation initiation factor 1A,X-linked(EIF1AX)genes as well as the MAPK/ERK signaling pathway genes,have been largely associated with the development of UM.Chromosomal aberrations,inflammatory and immunological alterations are often concurrent factors for the development and progression of UM.Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs.This review aims to present the latest advances in the clinical molecular pathology of UM,along with the resulting targeted,immunological,and other therapies that have been introduced or are currently under investigation.
基金supported by a grant from the Japan Foundation for applied enzymology (to NT)the Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (26430059, 17K08272, and 20K07014 to NT)+1 种基金the establishment of university fellowships toward the creation of science technology innovation (JPMJFS2128)a Grant-in-Aid for JSPS Fellows (23KJ1603)(to MK)。
文摘The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
基金supported by the Japan Society for the Promotion of Science(JSPS KAKENHI Grant Number 24K12615).
文摘Ovarian endometrioid carcinoma(OEC)accounts for~10%of epithelial ovarian cancers and displays broad morphologic diversity that complicates diagnosis and grading.Recent data show that the endometrial cancer molecular taxonomy(DNA polymerase epsilon,catalytic subunit[POLE]-ultramutated,mismatch repair-deficient[MMRd],p53-abnormal,no specific molecular profile[NSMP])also applies to OEC,and that OEC is enriched for Lynch syndrome–associated tumors,supporting routine MMR testing.We aimed to synthesize contemporary evidence spanning epidemiology,histopathology and immunophenotype,diagnostic pitfalls and differential diagnosis,and to evaluate the clinical utility of The Cancer Genome Atlas(TCGA)-surrogate molecular classification for risk stratification;we also summarize implications for Lynch screening,genetic counseling,and therapeutic opportunities including immune checkpoint inhibitors and targeted approaches,with practical recommendations for diagnostic workflows.Integrating morphology with molecular classification refines diagnosis and prognostication:POLEmut/MMRd subsets generally have excellent outcomes and are candidates for de-escalation or immunotherapy,whereas p53abn/high-grade tumors carry a poorer prognosis and may warrant intensified management and trials of homologous recombination deficiency(HRD)-directed strategies;routine MMR immunohistochemistry(IHC)with reflex germline testing improves Lynch detection,and future priorities include prospective validation and multi-omics to refine NSMP and identify new targets.
文摘A recent study by Luo et al examined the relationship between the pathological types of pancreatic cancer(PC)and their imaging characteristics.While this study presented an important step toward improving diagnostic accuracy for PC,we have several concerns regarding its generalizability,cohort selection,imaging variability,statistical methods,and potential confounding factors.We recommended that future research adopt multi-center,prospective designs to improve representation and minimize bias.Additionally,incorporating advanced imaging techniques such as radiomics and artificial intelligence and conducting more comprehensive statistical analyses would be valuable.By implementing these strategies,future studies can yield more reliable and externally validated findings that improve the clinical applicability of imaging-based differentiation of PC.Addressing these methodological issues could significantly advance the field of gastrointestinal oncology and improve patient management and outcomes.
文摘AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening of the GSE24673 and GSE125903 datasets,combined with GeneCards database analysis.A total of 102 RB patients and 62 traumaenucleated controls between January 2018 and December 2023 were enrolled,with their clinicopathological data and retinal tissues collected.The mRNA and methylation levels of MSH6 in retinal tissues were detected using real-time quantitative polymerase chain reaction(PCR)and methylation-specific PCR.Western blot analysis was conducted in one pair of RB and control tissues for preliminary protein-level validation of MSH6 expression.Based on the methylation status of MSH6,RB patients were categorized into two groups:low-methylation and highmethylation.Both univariate and multivariate analyses were conducted to identify independent factors influencing the methylation levels using clinicopathological data.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic potential of MSH6 methylation in RB.RESULTS:Bioinformatics analysis of public datasets revealed that MSH6 expression was downregulated across multiple cancers,RB.Consistently,in clinical RB tissues,MSH6 mRNA expression was significantly lower than that in control retinal tissues,whereas the promoter methylation level of MSH6 was markedly higher(both P<0.001),indicating that promoter hypermethylation may contribute to transcriptional silencing of MSH6 in RB.Patients with higher MSH6 methylation levels showed more advanced pathological classification and a higher frequency of metastasis.Multivariate logistic regression confirmed that metastatic status(P=0.008,OR=3.51)and pathological classification(P=0.005,OR=3.7)were independent factors associated with MSH6 methylation.Receiver operating characteristic(ROC)analysis demonstrated that MSH6 methylation could effectively distinguish RB tissues from non-tumorous controls(AUC=0.847,sensitivity=78.43%,specificity=80.65%),suggesting that MSH6 hypermethylation may serve as a potential diagnostic biomarker for RB.CONCLUSION:The methylation level of the MSH6 gene may be a key factor in RB pathogenesis.The methylation status of the MSH6 gene is closely associated with clinicopathological features and shows diagnostic potential.
文摘Objective:To enhance the reading skills of clinical pathology residents,it is essential to establish a well-structured electronic pathology reading library.Methods:In accordance with the Resident Standardization Training Content and Standards(2022 Edition),clinical pathology residents are required to master pathological diagnoses across 11 systems:skin,head and neck,mediastinum and respiratory,digestive,urinary and male reproductive,female reproductive and breast,lymphatic and hematopoietic,bone and soft tissue,cardiovascular,central nervous,and endocrine diseases.Senior pathologists specializing in each subspecialty selected classic pathological slides,which were systematically scanned and compiled into an electronic pathology library.Results:A questionnaire survey was conducted to gather feedback on the electronic pathology reading library.Residents generally found it to be convenient,efficient,and conducive to learning.Conclusion:Training in clinical pathology diagnosis is a core component of standardized resident training.The electronic pathology reading library has been well-received and recognized by resident doctors.However,further efforts are needed to explore diverse teaching methods that align with modern educational approaches,ultimately contributing to the development of highly skilled resident doctors.
文摘BACKGROUND The heterogeneous group of disorders called peripheral vascular diseases(PVDs)occurs outside the heart and brain tissue to cause ischemia and severe health complications.Diagnosis accuracy is essential in starting appropriate patient management at the proper time.Modern medicine considers skin biopsies crucial diagnostic tools that yield histopathological and molecular evidence for examining PVD-related microvascular changes.AIM To evaluate skin biopsy applications in PVD diagnostics through artistic analysis of technical processes and examination of pathological and innovative molecular indicators.METHODS A systematic review of randomized controlled trials and original studies about skin biopsy utility in PVD diagnosis used PubMed,Scopus,and EMBASE search platforms.The reviewed studies met specific entry requirements,while all case reports and review articles remained excluded.RESULTS A total of 22 studies suited the research criteria that were evaluated.Researchers emphasized the value of skin biopsies for identifying inflammatory from non-inflammatory PVDs.At the same time,they detect systemic sclerosis and diabetic vasculopathy abnormalities of micro-vessels and identify endothelial dysfunction through measurements of vascular endothelial growth factor and intercellular adhesion molecule-1 and endothelial nitric oxide synthase markers.Skin biopsies require further improvement because they cause patient discomfort and produce variable diagnostic results that specialists must interpret.CONCLUSION Skin biopsies enable essential diagnostic findings about PVD and improve patient detection.The development of standardized biopsy procedures and molecular diagnosis techniques should be studied to advance PVD diagnoses in clinical practice.
文摘Dear Editor,We aimed to describe the management of the intraoperative injury of the right external iliac artery that occurred during robot-assisted right nephroureterectomy with bladder cuff excision.Surgery was scheduled for suspected urothelial carcinoma of the distal ureter in a 60-year-old woman.The patient involved in the present research signed a dedicated form to consent to the publication of images and/or information about her.Past medical history included Brugada syndrome diagnosed in 2015,and hypercholesterolemia.Past surgical history included one cesarean section only.Family history included ovarian cancer(sister),colorectal cancer(mother),and kidney cancer(father).
基金supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2025R104),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘One in every eight men in the US is diagnosed with prostate cancer,making it the most common cancer in men.Gleason grading is one of the most essential diagnostic and prognostic factors for planning the treatment of prostate cancer patients.Traditionally,urological pathologists perform the grading by scoring the morphological pattern,known as the Gleason pattern,in histopathology images.However,thismanual grading is highly subjective,suffers intra-and inter-pathologist variability and lacks reproducibility.An automated grading system could be more efficient,with no subjectivity and higher accuracy and reproducibility.Automated methods presented previously failed to achieve sufficient accuracy,lacked reproducibility and depended on high-resolution images such as 40×.This paper proposes an automated Gleason grading method,ProGENET,to accurately predict the grade using low-resolution images such as 10×.This method first divides the patient’s histopathology whole slide image(WSI)into patches.Then,it detects artifacts and tissue-less regions and predicts the patch-wise grade using an ensemble network of CNN and transformer models.The proposed method adapted the International Society of Urological Pathology(ISUP)grading system and achieved 90.8%accuracy in classifying the patches into healthy and Gleason grades 1 through 5 using 10×WSI,outperforming the state-of-the-art accuracy by 27%.Finally,the patient’s grade was determined by combining the patch-wise results.The method was also demonstrated for 4−class grading and binary classification of prostate cancer,achieving 93.0%and 99.6%accuracy,respectively.The reproducibility was over 90%.Since the proposedmethod determined the grades with higher accuracy and reproducibility using low-resolution images,it is more reliable and effective than existing methods and can potentially improve subsequent therapy decisions.
基金Supported by First-class Curriculum"Plant Immunology"Project of Tianjin Agricultural University.
文摘Using the curriculum of horticultural plant pathology as a starting point,this paper investigates the collaborative education model of"curriculum ideology and politics+innovation and entrepreneurship".It expounds the necessity of constructing this model,proposes implementation paths from aspects such as the integration of ideological and political elements,the cultivation of innovation and entrepreneurship capabilities,and the construction of a collaborative education mechanism.Furthermore,it analyzes the practical effects,challenges encountered,and corresponding response strategies,thereby offering a valuable reference for the training of professionals in horticulture.
基金Supported by National Natural Science Foundation of China(No.82201171,No.82171050,No.82471072).
文摘AIM:To describe the alterations of the vitreous pathology and anterior chamber(AC)angle structures following transscleral cyclophotocoagulation(TSCP)and better understand the mechanism of post-laser intraocular pressure(IOP)reduction in angle-closure glaucoma(ACG).METHODS:Porcine eyes ex vivo and rabbit eyes in vivo were used.In porcine eyes,permeability rates of the anterior vitreous cortex(AVC)and anterior hyaloid membrane(AHM)were assessed using Schirmer’s strips.Permeability rates in the circumlental space were compared with or without TSCP bursts.Fluorescein diffusion times from the vitreous to the AC were compared between eyes with and without TSCP.In rabbit eyes,changes in IOP and AC angle structures under ultrasound biomicroscopy(UBM)were evaluated at intervals of 30min,7d,and 14d after TSCP.Vitreous pathology was examined using scanning electron microscopy(SEM)immediately and 14d after TSCP.RESULTS:In porcine eyes(n=20),the median(range)permeability rates were 10.3(range 9.8–10.8)mm/min for the AVC and 4.3(range 3.9–4.9)mm/min for the AHM(P=0.009).Permeability rates in the circumlental space were 4.2(range 3.8–4.9)mm/min in areas without TSCP,6.2(range 5.7–6.8)mm/min in areas with non-burst TSCP,and 11.3(range 10.9–11.8)mm/min in areas with burst TSCP(P=0.002).The median(range)fluorescein diffusion time was 5(range 3–8)min in eyes undergoing TSCP,whereas it was 40min(range 35–68)in eyes without TSCP(P<0.001).In rabbit eyes(n=20),SEM showed immediate localized damage to the AHM,AVC,and posterior lens zonules in areas subjected to TSCP bursts,and obvious lens zonule loss with cellular infiltration and possible vitreous liquefaction by post-op day 14.Persistent widening of AC angles was noted at postoperative days 7 and 14,although a significant reduction in IOP was only observed at postoperative day 7.CONCLUSION:TSCP-induced damage on the zonules,AHM,and AVC potentially enhances fluid outflow from the vitreous,leading to a widened AC angle and vitreous liquefaction in rabbits.These observations offer insights into mechanisms of TSCP in lowering IOP and pathogenic roles of vitreous in ACG.
