Objective: to explore the application effect of case introduction teaching in the standardized training of pathologists. Methods: eight standardized training physicians who attended the standardized training in the de...Objective: to explore the application effect of case introduction teaching in the standardized training of pathologists. Methods: eight standardized training physicians who attended the standardized training in the department of pathology of our hospital from January 2016 to February 2022 were selected as the research objects. They were randomly divided into two groups to carry out the research, i.e. the control group and the observation group with 4 cases in each group. The former group adopted the conventional teaching method, while the latter group adopted the case-introduction teaching method. The evaluation results of theoretical knowledge and practical ability of the two groups of standardized training physicians before and after the teaching were compared. The comprehensive ability improvement, satisfaction and teaching effect evaluation of the standardized training physicians for different teaching methods were investigated by means of questionnaire. Results: the theoretical knowledge and practical skills of the two groups were improved after teaching. The comparison between the two groups showed that the scores of theoretical knowledge and practical skills of the observation group were better than those of the control group (P 0.05). Compared with the control group, the observation group had statistical significance in improving learning interest, improving autonomous learning ability and improving the ability to solve clinical problems (P 0.05). The total satisfaction of the observation group was 100.00%, significantly higher than that of the control group (50.00%), but there was no statistical difference between the groups (P > 0.05). The standardized training doctors in the observation group scored significantly better than that in the control group (P 0.05). Conclusion: the standardized training of doctors in pathology department can not only improve their overall scores, but also improve their comprehensive ability, and achieve satisfactory teaching results.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
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
Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in...Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.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
BACKGROUND SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma is a highly aggressive tumor,and spontaneous splenic rupture(SSR)as its presenting manifestation is rarely reported among pancreatic mal...BACKGROUND SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma is a highly aggressive tumor,and spontaneous splenic rupture(SSR)as its presenting manifestation is rarely reported among pancreatic malignancies.CASE SUMMARY We herein report a rare case of a 59-year-old female who presented with acute left upper quadrant abdominal pain without any history of trauma.Abdominal imaging demonstrated a heterogeneous splenic lesion with hemoperitoneum,raising clinical suspicion of SSR.Emergency laparotomy revealed a pancreatic tumor invading the spleen and left kidney,with associated splenic rupture and dense adhesions,necessitating en bloc resection of the distal pancreas,spleen,and left kidney.Histopathology revealed a biphasic malignancy composed of moderately differentiated pancreatic ductal adenocarcinoma and an undifferentiated carcinoma with rhabdoid morphology and loss of SMARCB1 expression.Immunohistochemical analysis confirmed complete loss of SMARCB1/INI1 in the undifferentiated component,along with a high Ki-67 index(approximately 80%)and CD10 positivity.The ductal adenocarcinoma component retained SMARCB1/INI1 expression and was positive for CK7 and CK-pan.Transitional zones between the two tumor components suggested progressive dedifferentiation and underlying genomic instability.The patient received adjuvant chemotherapy with gemcitabine and nab-paclitaxel and maintained a satisfactory quality of life at the 6-month follow-up.CONCLUSION This study reports a rare case of SMARCB1/INI1-deficient undifferentiated rhabdoid carcinoma of the pancreas combined with ductal adenocarcinoma,presenting as SSR-an exceptionally uncommon initial manifestation of pancreatic malignancy.展开更多
Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive com...Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.展开更多
Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protei...Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
Objective:To characterize placental morphologic features in Moroccan women with adverse outcomes,across different clinical contexts,based on the Amsterdam consensus classification.Methods:A prospective analysis was co...Objective:To characterize placental morphologic features in Moroccan women with adverse outcomes,across different clinical contexts,based on the Amsterdam consensus classification.Methods:A prospective analysis was conducted on placentas with umbilical cords collected fresh between March 1,2024 and July 15,2024 from women with adverse pregnancy outcomes.Clinical data(age,parity,gravidity,complications)were retrieved.Macroscopic parameters(weight,dimensions,cord insertion,membranes,lesions)were assessed,followed by systematic sampling.Tissue was processed by standard histology(formalin fixation,paraffin embedding,hematoxylin and eosin staining),and lesions were classified per Amsterdam criteria.Results:16 placentas from patients with adverse pregnancy outcomes were included.The median maternal age was 30 years.Adverse conditions included placental abruption(50%),intrauterine growth restriction(IUGR,38%),intrauterine fetal death(IUFD,31%),pre-eclampsia/eclampsia(19%),premature rupture of membranes(13%),and oligohydramnios(13%).Several placentas were associated with more than one adverse condition.Histopathology revealed maternal vascular malperfusion lesions in 94%,particularly in pre-eclampsia,IUGR,and IUFD.Fetal vascular malperfusion was found in 88%,mainly in IUGR and IUFD.Inflammatory lesions,dominated by acute maternal and fetal responses stage 3(necrotizing chorioamnionitis and funisitis),were primarily linked to IUFD.Conclusions:Placental examination enhances understanding of the pathophysiology underlying adverse pregnancy outcomes,supports diagnostic confirmation,and guides preventive strategies for recurrence.This study highlights the prevalence of maternal vascular malperfusion in Moroccan women and emphasizes the importance of systematic placental histopathology in obstetric care.展开更多
Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance pati...Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.展开更多
Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience...Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.展开更多
Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified n...Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor...Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.展开更多
Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH),...Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma(HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC(SH-HCC), showsfeatures that resemble non-neoplastic steatohepatitis,and is thought to be strongly associated with underlying NASH.In this report,we review the histopathological features of NAFLD/NASH.展开更多
AIM： To investigate the myxoma peritonei （PMP） histological origin of pseudo- n Chinese women. METHODS： The clinical and pathological data were reviewed for 35 women with PMP, and specimens of the peritoneal, appe...AIM： To investigate the myxoma peritonei （PMP） histological origin of pseudo- n Chinese women. METHODS： The clinical and pathological data were reviewed for 35 women with PMP, and specimens of the peritoneal, appendiceal and ovarian lesions of each patient were examined using the PV-6000 immunohistochemistry method. Antibodies included cytokeratin （CK）7, CK20, mucin （MUC）-1, MUC-2, carbohydrate antigen （CA）-125, estrogen receptor （ER）, and progesterone receptor （PR）. RESULTS： Abundant colloidal mucinous tumors were observed in the peritoneum in all 35 cases. Thirty-one patients had a history of appendectomy, 28 of whom had mucinous lesions. There was one patient with appendicitis, one whose appendix showed no apparent pathological changes, and one with unknown surgical pathology. Ovarian mucinous tumors were found in 24 patients. The tumors were bilateral in 13 patients, on the right-side in nine, and on the left side in two. Twenty patients had combined appendiceal and ovarian lesions; 16 of whom had undergone initial surgery for appendiceal lesions. Four patients had undergone initial surgery for ovarian lesions, and relapse occurred in these patients at 1, 11, 32 and 85 mo after initial surgery. Appendi-ceal mucinous tumors were found in each of these four patients. Thirty-three of the 35 patients showed peritoneal lesions that were positive for CK20 and MUC-2, but negative for CK7, MUC-1, CA125, ER and PR. The expression patterns in the appendix and the ovary were similar to those of the peritoneal lesions. In one of the remaining two cases, CK20, CK7 and MUC-2 were positive, and MUC-1, CA125, ER and PR were negative. The ovaries were not resected. The appendix of one patient was removed at another hospital, and no specimen was evaluated. In the other case, the appendix appeared to be normal during surgery, and was not resected. Peritoneal and ovarian lesions were negative for CK20, MUC-2, CK7, MUC-1, CA125, ER and PR. CONCLUSION： Most PMP originated from the appendix. Among women with PMP, the ovarian tumors were implanted rather than primary. For patients with PMP, appendectomy should be performed routinely. The ovaries, especially the right ovaries should be explored.展开更多
文摘Objective: to explore the application effect of case introduction teaching in the standardized training of pathologists. Methods: eight standardized training physicians who attended the standardized training in the department of pathology of our hospital from January 2016 to February 2022 were selected as the research objects. They were randomly divided into two groups to carry out the research, i.e. the control group and the observation group with 4 cases in each group. The former group adopted the conventional teaching method, while the latter group adopted the case-introduction teaching method. The evaluation results of theoretical knowledge and practical ability of the two groups of standardized training physicians before and after the teaching were compared. The comprehensive ability improvement, satisfaction and teaching effect evaluation of the standardized training physicians for different teaching methods were investigated by means of questionnaire. Results: the theoretical knowledge and practical skills of the two groups were improved after teaching. The comparison between the two groups showed that the scores of theoretical knowledge and practical skills of the observation group were better than those of the control group (P 0.05). Compared with the control group, the observation group had statistical significance in improving learning interest, improving autonomous learning ability and improving the ability to solve clinical problems (P 0.05). The total satisfaction of the observation group was 100.00%, significantly higher than that of the control group (50.00%), but there was no statistical difference between the groups (P > 0.05). The standardized training doctors in the observation group scored significantly better than that in the control group (P 0.05). Conclusion: the standardized training of doctors in pathology department can not only improve their overall scores, but also improve their comprehensive ability, and achieve satisfactory teaching results.
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.
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Colorectal cancer(CRC)is one of the most molecularly heterogeneous malignancies,with complexity that extends far beyond traditional histopathological classifications.The consensus molecular subtypes(CMS)established in 2015 brought a marked advancement in the taxonomy of CRC,consolidating six classification systems into four novel subtypes,which focus on vital gene expression patterns and clinical and prognostic outcomes.However,nearly a decade of clinical experience with CMS classification has revealed fundamental limitations that underscore the inadequacy of any single classification system for capturing the full spectrum of CRC biology.The inherent challenges of the current paradigm are multifaceted.In the CMS classification,mixed phenotypes that remain unclassifiable constitute 13%of CRC cases.This reflects the remarkable heterogeneity that CRC shows.The tumor budding regions reflect the molecular shift due to CMS 2 to CMS 4 switching,causing further heterogeneity.Moreover,the reliance on bulk RNA sequencing fails to capture the spatial organization of molecular signatures within tumors and the critical contributions of the tumor microenvironment.Recent technological advances in spatial transcriptomics,singlecell RNA sequencing,and multi-omic integration have revealed the limitations of transcriptome-only classifications.The emergence of CRC intrinsic subtypes that attempt to remove microenvironmental contributions,pathway-derived subtypes,and stem cell-based classifications demonstrates the field’s recognition that multiple complementary classification systems are necessary.These newer molecular subtypes are not discrete categories but biological continua,thus highlighting that the vast molecular landscape is a tapestry of interlinked features,not rigid subtypes.Multiple technical hurdles cause difficulty in implementing the clinical translation of these newer molecular subtypes,including gene signature complexity,platform-dependent variations,and the difficulty of getting and preserving fresh frozen tissue.CMS 4 shows a poor prognostic outcome among the CMS subtypes,while CMS 1 is associated with poor survival in metastatic cases.However,the predictive value for definitive therapy remains subdued.Looking forward,the integration of artificial intelligence,liquid biopsy approaches,and real-time molecular monitoring promises to enable dynamic,multi-dimensional tumor characterization.The temporal and spatial complexity can only be captured by complementary molecular taxonomies rather than a single,unified system of CRC classification.Such an approach recognizes that different clinical questions–prognosis,treatment selection,resistance prediction–may require different molecular lenses,each optimized for specific clinical applications.This editorial advocates for a revolutionary change from pursuing a single“best”classification system toward a diverse approach that welcomes the molecular mosaic of CRC.Only through such comprehensive molecular characterization can we hope to achieve the promise of precision oncology for the diverse spectrum of patients with CRC.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
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.
文摘BACKGROUND SMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma is a highly aggressive tumor,and spontaneous splenic rupture(SSR)as its presenting manifestation is rarely reported among pancreatic malignancies.CASE SUMMARY We herein report a rare case of a 59-year-old female who presented with acute left upper quadrant abdominal pain without any history of trauma.Abdominal imaging demonstrated a heterogeneous splenic lesion with hemoperitoneum,raising clinical suspicion of SSR.Emergency laparotomy revealed a pancreatic tumor invading the spleen and left kidney,with associated splenic rupture and dense adhesions,necessitating en bloc resection of the distal pancreas,spleen,and left kidney.Histopathology revealed a biphasic malignancy composed of moderately differentiated pancreatic ductal adenocarcinoma and an undifferentiated carcinoma with rhabdoid morphology and loss of SMARCB1 expression.Immunohistochemical analysis confirmed complete loss of SMARCB1/INI1 in the undifferentiated component,along with a high Ki-67 index(approximately 80%)and CD10 positivity.The ductal adenocarcinoma component retained SMARCB1/INI1 expression and was positive for CK7 and CK-pan.Transitional zones between the two tumor components suggested progressive dedifferentiation and underlying genomic instability.The patient received adjuvant chemotherapy with gemcitabine and nab-paclitaxel and maintained a satisfactory quality of life at the 6-month follow-up.CONCLUSION This study reports a rare case of SMARCB1/INI1-deficient undifferentiated rhabdoid carcinoma of the pancreas combined with ductal adenocarcinoma,presenting as SSR-an exceptionally uncommon initial manifestation of pancreatic malignancy.
文摘Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.
文摘Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
文摘Objective:To characterize placental morphologic features in Moroccan women with adverse outcomes,across different clinical contexts,based on the Amsterdam consensus classification.Methods:A prospective analysis was conducted on placentas with umbilical cords collected fresh between March 1,2024 and July 15,2024 from women with adverse pregnancy outcomes.Clinical data(age,parity,gravidity,complications)were retrieved.Macroscopic parameters(weight,dimensions,cord insertion,membranes,lesions)were assessed,followed by systematic sampling.Tissue was processed by standard histology(formalin fixation,paraffin embedding,hematoxylin and eosin staining),and lesions were classified per Amsterdam criteria.Results:16 placentas from patients with adverse pregnancy outcomes were included.The median maternal age was 30 years.Adverse conditions included placental abruption(50%),intrauterine growth restriction(IUGR,38%),intrauterine fetal death(IUFD,31%),pre-eclampsia/eclampsia(19%),premature rupture of membranes(13%),and oligohydramnios(13%).Several placentas were associated with more than one adverse condition.Histopathology revealed maternal vascular malperfusion lesions in 94%,particularly in pre-eclampsia,IUGR,and IUFD.Fetal vascular malperfusion was found in 88%,mainly in IUGR and IUFD.Inflammatory lesions,dominated by acute maternal and fetal responses stage 3(necrotizing chorioamnionitis and funisitis),were primarily linked to IUFD.Conclusions:Placental examination enhances understanding of the pathophysiology underlying adverse pregnancy outcomes,supports diagnostic confirmation,and guides preventive strategies for recurrence.This study highlights the prevalence of maternal vascular malperfusion in Moroccan women and emphasizes the importance of systematic placental histopathology in obstetric care.
文摘Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.
基金supported by the National Natural Science Foundation of China,No.31760290,82160688the Key Development Areas Project of Ganzhou Science and Technology,No.2022B-SF9554(all to XL)。
文摘Synaptic pruning is a crucial process in synaptic refinement,eliminating unstable synaptic connections in neural circuits.This process is triggered and regulated primarily by spontaneous neural activity and experience-dependent mechanisms.The pruning process involves multiple molecular signals and a series of regulatory activities governing the“eat me”and“don't eat me”states.Under physiological conditions,the interaction between glial cells and neurons results in the clearance of unnecessary synapses,maintaining normal neural circuit functionality via synaptic pruning.Alterations in genetic and environmental factors can lead to imbalanced synaptic pruning,thus promoting the occurrence and development of autism spectrum disorder,schizophrenia,Alzheimer's disease,and other neurological disorders.In this review,we investigated the molecular mechanisms responsible for synaptic pruning during neural development.We focus on how synaptic pruning can regulate neural circuits and its association with neurological disorders.Furthermore,we discuss the application of emerging optical and imaging technologies to observe synaptic structure and function,as well as their potential for clinical translation.Our aim was to enhance our understanding of synaptic pruning during neural development,including the molecular basis underlying the regulation of synaptic function and the dynamic changes in synaptic density,and to investigate the potential role of these mechanisms in the pathophysiology of neurological diseases,thus providing a theoretical foundation for the treatment of neurological disorders.
基金supported by grants from the Ministry of Science and Technology,Taiwan(MOST108-2314-B-182-006,MOST109-2314-B-182-071:Lee-Yung Shih)the Ministry of Health and Welfare,Taiwan(MOHW110-TDU-B-212-134011:Lee-Yung Shih)+3 种基金Chang Gung Memorial Hospital(CMRPG3D1524,OMRPG3E0031:Lee-Yung Shih)the Grant-in-Aid for the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP19H05656:Seishi Ogawa,22K16320:Yotaro Ochi)the Japan Agency for Medical Research and Development(AMED)(JP19cm0106501h0004,JP19ck0106250h0003:Seishi Ogawa)the Ministry of Education,Culture,Sports,Science and Technology of Japan(MEXT)(hp200138,hp210167:Seishi Ogawa)。
文摘Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
文摘Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.
文摘Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma(HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC(SH-HCC), showsfeatures that resemble non-neoplastic steatohepatitis,and is thought to be strongly associated with underlying NASH.In this report,we review the histopathological features of NAFLD/NASH.
文摘AIM： To investigate the myxoma peritonei （PMP） histological origin of pseudo- n Chinese women. METHODS： The clinical and pathological data were reviewed for 35 women with PMP, and specimens of the peritoneal, appendiceal and ovarian lesions of each patient were examined using the PV-6000 immunohistochemistry method. Antibodies included cytokeratin （CK）7, CK20, mucin （MUC）-1, MUC-2, carbohydrate antigen （CA）-125, estrogen receptor （ER）, and progesterone receptor （PR）. RESULTS： Abundant colloidal mucinous tumors were observed in the peritoneum in all 35 cases. Thirty-one patients had a history of appendectomy, 28 of whom had mucinous lesions. There was one patient with appendicitis, one whose appendix showed no apparent pathological changes, and one with unknown surgical pathology. Ovarian mucinous tumors were found in 24 patients. The tumors were bilateral in 13 patients, on the right-side in nine, and on the left side in two. Twenty patients had combined appendiceal and ovarian lesions; 16 of whom had undergone initial surgery for appendiceal lesions. Four patients had undergone initial surgery for ovarian lesions, and relapse occurred in these patients at 1, 11, 32 and 85 mo after initial surgery. Appendi-ceal mucinous tumors were found in each of these four patients. Thirty-three of the 35 patients showed peritoneal lesions that were positive for CK20 and MUC-2, but negative for CK7, MUC-1, CA125, ER and PR. The expression patterns in the appendix and the ovary were similar to those of the peritoneal lesions. In one of the remaining two cases, CK20, CK7 and MUC-2 were positive, and MUC-1, CA125, ER and PR were negative. The ovaries were not resected. The appendix of one patient was removed at another hospital, and no specimen was evaluated. In the other case, the appendix appeared to be normal during surgery, and was not resected. Peritoneal and ovarian lesions were negative for CK20, MUC-2, CK7, MUC-1, CA125, ER and PR. CONCLUSION： Most PMP originated from the appendix. Among women with PMP, the ovarian tumors were implanted rather than primary. For patients with PMP, appendectomy should be performed routinely. The ovaries, especially the right ovaries should be explored.
