The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It ha...The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).展开更多
Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treat...Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treatment and nursing care have greatly improved the life expectancy of individuals with DS.However,as they age,their risk of developing Alzheimer’s disease(AD)increases considerably(Antonarakis et al.,2020).展开更多
Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially me...Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially mesenchymal stem cells(MSCs),has surfaced as a viable approach for tissue regeneration and immunological regulation in DED.Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality,diminish inflammation,and facilitate corneal regeneration.Nonetheless,obstacles persist in enhancing MSC viability,determining the optimal MSC source,and guaranteeing sustained therapeutic effectiveness.Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.展开更多
Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose a...Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular networks.Brain vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the brain.This elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing vasculature.Brain capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.展开更多
“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging...“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.展开更多
BACKGROUND Disorders of gut-brain interaction(DGBI)are common,but knowledge about their physiopathology is still poor,nor valid tools have been used to evaluate them in childhood.AIM To develop a psycho-gastroenterolo...BACKGROUND Disorders of gut-brain interaction(DGBI)are common,but knowledge about their physiopathology is still poor,nor valid tools have been used to evaluate them in childhood.AIM To develop a psycho-gastroenterological questionnaire(PGQ)to assess the psycho-gastroenterological profile and social characteristics of a pediatric population with and without DGBI.METHODS One hundred and nineteen Italian children(age 11-18)were included:28 outpatient patients with DGBI(Rome IV criteria)and 91 healthy controls.They filled the PGQ,faces pain scale revised(FPS-R),Bristol stool chart,ga-strointestinal symptoms rating scale,state-trait anxiety inventory,Toronto alexithymia scale 20,perceived self-efficacy in the management of negative emotions and expression of positive emotions(APEN-G,APEP-G),irritable bowel syndrome-quality of life questionnaire,school performances,tobacco use,early life events,degree of digital-ization.RESULTS Compared to controls,patients had more medical examinations(35%of them went to the doctor more than five times),a higher school performance(23%vs 13%,P<0.05),didn’t use tobacco(never vs 16%,P<0.05),had early life events(28%vs 1%P<0.05)and a higher percentage of pain classified as 4 in the FPS-R during the examination(14%vs 7%,P<0.05).CONCLUSION Pediatric outpatients with DGBI had a higher prevalence of early life events,a lower quality of life,more medical examinations rising health care costs,lower anxiety levels.展开更多
Peyronie's disease(PD)is a challenging condition that significantly impacts male sexual health,often leading to penile curvature,pain,and erectile dysfunction.Treatment options range from conservative pharmacologi...Peyronie's disease(PD)is a challenging condition that significantly impacts male sexual health,often leading to penile curvature,pain,and erectile dysfunction.Treatment options range from conservative pharmacologic approaches to more invasive surgical interventions,with collagenase clostridium histolyticum(CCH)being the only U.S.Food and Drug Administration(FDA)-approved intralesional therapy.However,optimizing treatment strategies to enhance efficacy while minimizing patient burden remains an area of ongoing investigation.^(1,2)展开更多
Premenstrual and menstrual exacerbation of psychiatric disorders is a significant area of concern in female mental health.Many females experience a worsening of psychiatric symptoms in the premenstrual and menstrual p...Premenstrual and menstrual exacerbation of psychiatric disorders is a significant area of concern in female mental health.Many females experience a worsening of psychiatric symptoms in the premenstrual and menstrual phases of their menstrual cycle,including heightened anxiety,depression,irritability,and mood swings.These exacerbations are most commonly associated with premenstrual syndrome and premenstrual dysphoric disorder that are characterized by severe emotional and physical symptoms that interfere with daily functioning.The hormonal fluctuations during the menstrual cycle,particularly changes in estrogen and progesterone levels,are believed to play a pivotal role in these exacerbations.Psychiatric disorders such as depression,anxiety,bipolar disorder,and schizophrenia may be influenced by these hormonal changes,with many females reporting an increase in symptom severity during specific phases of the cycle.The mechanisms behind this phenomenon remain complex,with both biological and psychosocial factors contributing to the heightened vulnerability.Clinical management includes careful monitoring of symptom patterns in relation to the menstrual cycle,with treatment options ranging from lifestyle modifications and psychotherapy to pharmacological interventions such as antidepressants and hormonal therapies.Understanding the link between menstruation and psychiatric disorders is essential for improving diagnosis and tailoring effective treatment strategies for affected individuals.展开更多
Mourning and grief are natural responses to loss and can be especially complex and prolonged in the context of end-of-life care.Caregivers play a crucial role in supporting individuals through this difficult journey,o...Mourning and grief are natural responses to loss and can be especially complex and prolonged in the context of end-of-life care.Caregivers play a crucial role in supporting individuals through this difficult journey,often balancing their own grief with the need to provide care.This paper explores the experiences of mourning and grief in hospice settings,with a focus on the emotional challenges faced by both patients and caregivers during the grieving process.Psychological support plays a crucial role at the end of life in a multidisciplinary care approach.By addressing the complex interplay between biological disease and psychological well-being,healthcare professionals can provide more comprehensive and compassionate care.A deep understanding of mourning and elaboration of grief would improve the implementation of suitable support interventions and facilitate collaboration among family members and healthcare teams,ultimately improving the quality of end-of-life care and promoting the well-being of both patients and their families.展开更多
The gut microbiota plays a pivotal role in human health,influencing diverse physiological processes,including those related to sexual health.Emerging evidence suggests a bidirectional relationship between the gut micr...The gut microbiota plays a pivotal role in human health,influencing diverse physiological processes,including those related to sexual health.Emerging evidence suggests a bidirectional relationship between the gut microbiota and sexual health,mediated by its impact on systemic inflammation,hormonal regulation,and immune function.A balanced gut microbiota supports optimal levels of sex hormones,such as estrogen and testosterone,which are critical for sexual function and reproductive health.Additionally,gut-derived metabolites such as short-chain fatty acids contribute to maintaining mucosal barrier integrity and regulating immune responses,which are essential for protecting against infections that may impair sexual health.Conversely,dysbiosis,an imbalance in gut microbial composition,has been linked to conditions such as erectile dysfunction,polycystic ovary syndrome,and reduced libido,emphasizing its role in sexual dysfunction.Lifestyle factors,including diet,stress,and antibiotic use,can modulate the gut microbiota and,consequently,sexual health outcomes.Recent therapeutic approaches,such as probiotics,prebiotics,and fecal microbiota transplantation,offer potential for restoring gut balance and improving sexual health.This review highlights the central role of the gut microbiota in sexual health,emphasizing its importance as a target for therapeutic interventions to enhance overall well-being.展开更多
AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated ...AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated with intravitreal aflibercept.METHODS:OCT data collected at the time of nAMD diagnosis(T0),after the first(T1)and third(T2)intravitreal aflibercept injection,and 5y post-diagnosis(T3)were analyzed.The study included 46 eyes from patients undergoing treatment.The association of OCT features with RA and visual acuity(VA)development over time were evaluated.RESULTS:Patients with RA at T3 exhibited worse VA(35.19±5.7 vs 8.90±2.3,P<0.001)and a lower rate of improvement or stability at T2(90.48%vs 56.00%,P=0.019)and T3(85.71%vs 8.00%,P<0.001).The development of RA at T3 was linked with type 2 macular neovascularization(MNV;4.76%vs 36.00%,P=0.013),thinner outer nuclear layer(ONL,88.89±7.82μm vs 71.38±14.14μm,P=0.033),presence of intraretinal fluid(IRF,42.86%vs 80.00%,P=0.014),presence of IRF without subretinal fluid at T0(SRF,4.76%vs 32.00%,P=0.027),and reduced central foveal thickness at T3(CFT,190.14±22.79μm vs 124.32±14.35μm,P<0.001).The presence of SRF with or without IRF at the diagnosis was comparable between the two groups(90.48%vs 68.00%;P=0.084).CONCLUSION:Type 2 MNV,reduces ONL and CFT,and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients,underscoring the importance of these OCT features in early risk assessment and management strategies.展开更多
Pelvic fractures are rare but severe injuries that severely affect patients’quality of life.Treatment of these fractures often involves invasive approaches with high risk of injuries to nervous structures,particularl...Pelvic fractures are rare but severe injuries that severely affect patients’quality of life.Treatment of these fractures often involves invasive approaches with high risk of injuries to nervous structures,particularly lumbosacral plexus.The introduction of minimally invasive surgical approaches,such as the lateral rectus approach,not only contributes to preserving lumbar plexus integrity in operated patients but also positively impacts their psychological well-being.Patients treated by surgical reduction of pelvic fractures with lumbosacral plexus injury often experience states of anxiety and depression.The lateral rectus approach is associated with lower levels of anxiety and depression compared to more invasive surgical techniques used for similar fractures.展开更多
Dear Editor,Robot-assisted partial nephrectomy(RAPN)has become the preferred surgical treatment for most renal tumors[1].Local recurrences occur in 1%-10% of patients undergoing partial nephrectomy,and they tend to ap...Dear Editor,Robot-assisted partial nephrectomy(RAPN)has become the preferred surgical treatment for most renal tumors[1].Local recurrences occur in 1%-10% of patients undergoing partial nephrectomy,and they tend to appear within the first 5 years after surgery[2].展开更多
Background:Adult medulloblastoma(MB)represents less than 1%of central nervous system malignancies,lacking standardized therapeutic approaches due to its rarity.This retrospective single-center analysis aimed to assess...Background:Adult medulloblastoma(MB)represents less than 1%of central nervous system malignancies,lacking standardized therapeutic approaches due to its rarity.This retrospective single-center analysis aimed to assess survival outcomes and treatment-associated toxicities in adult MB patients managed with pediatric-derived protocols.Methods:Eighteen patients(≥18 years)with MB treated at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)(January 1997–January 2024)were analyzed.All received craniospinal radiotherapy with posterior fossa boost,followed by adjuvant chemotherapy utilizing pediatric regimens(PNET3,PNET4,PNET5,or high-risk protocols incorporating high-dose chemotherapy with autologous stem cell rescue).Primary outcomes included overall survival(OS)and progression-free survival(PFS).Secondary analyses focused on comprehensive toxicity assessment.Results:The cohort included 11 males and 7 females(median age:23 years).Metastatic disease was present in 6 patients(33%)at diagnosis.Histopathological distribution showed classic MB(55.5%),desmoplastic/nodular(39%),and large cell/anaplastic variants(5.5%).Molecular subgrouping(available in 6 patients)identified SHH subgroup in four cases and WNT subgroup in two.Three-year and fiveyear overall survival rates reached 94.5%and 88.8%,respectively.Treatment-related adverse events included grade 3–4 hematologic toxicities,clinically significant weight loss,and grade≥3 neurological and ototoxic complications.These toxicities necessitated treatment modifications including dose adjustments,cycle delays,and occasional early discontinuation.Conclusions:Adult MB patients treated with pediatric-adapted protocols demonstrated excellent long-termsurvival outcomes,comparable to or surpassing historical data.Despite frequent toxicity requiring treatment modifications,these regimens proved feasible with acceptable risk-benefit profiles.These results support implementing modified pediatric protocols for adult MB management.Future multicenter investigations with larger cohorts are essential for refining risk stratification,optimizing treatment intensity,and evaluating long-term outcomes in this rare malignancy.展开更多
Objective:Pelvic organ-sparing surgery aims to preserve vital reproductive and sexual organs,enhancing quality of life,especially in premenopausal women.Pelvic organ preservation for female patients undergoing radical...Objective:Pelvic organ-sparing surgery aims to preserve vital reproductive and sexual organs,enhancing quality of life,especially in premenopausal women.Pelvic organ preservation for female patients undergoing radical cystectomy is now emphasized for sexual and hormonal function.Recent screening studies show no survival advantage despite early diagnosis of ovarian cancer,but opportunistic salpingectomy could reduce high-grade serous carcinoma risk.The aim of this review was to analyze the incidence of metachronous or delayed ovarian cancer in patients undergoing radical cystectomy for bladder cancer.Methods:PubMed,Scopus,Web of Science,ClinicalTrials.gov,and Cochrane Library were searched systematically for English-language articles up to June 2024.The selection was done first by title and abstract screening and then by full-text assessment for eligibility.This review has been registered in PROSPERO(CRD42024561902).Results:This review included two retrospective studies(2211 patients).Most patients had local or regional advanced disease,with a minority having distant disease.Only one study reported direct pelvic organ involvement from urothelial cancer,with no ovarian involvement found.Among patients who had organ-sparing surgery or pelvic exenteration,only two developed ovarian cancer post-surgery.No mean follow-up time or side effects from pelvic organ removal were reported in either study.Conclusion:When oncologically safe,ovarian-sparing surgery with salpingectomy should be considered in female bladder cancer patients undergoing radical cystectomy.Opportunistic salpingectomy should be encouraged during abdominal urological surgeries,with thorough preoperative counseling guiding decisions.Further studies are needed to define the role of preventive gynecologic surgery in urologic procedures.展开更多
BACKGROUND Pituitary neuroendocrine tumors(PitNETs),formerly referred to as pituitary adenomas,are prevalent intracranial neoplasms that,although often benign histologically,can demonstrate invasive growth,therapeutic...BACKGROUND Pituitary neuroendocrine tumors(PitNETs),formerly referred to as pituitary adenomas,are prevalent intracranial neoplasms that,although often benign histologically,can demonstrate invasive growth,therapeutic resistance,and recurrence.Emerging evidence supports the presence of a subpopulation of tumorinitiating cells with stem-like properties-pituitary adenoma stem cells(PASCs)-that may drive these aggressive features.This systematic review aims to critically examine the evidence on PASCs,their phenotypic and functional characteristics,and their role in PitNET pathophysiology.AIM To study the molecular markers,signaling pathways,research models,and phenotypic traits of PASCs,and to assess their potential significance for future translational and clinical applications.METHODS A comprehensive literature search was conducted in PubMed,Scopus,and Ovid MEDLINE in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Thirty-four studies were included based on predefined eligibility criteria.Data were extracted regarding PASC isolation methods(e.g.,neurosphere formation,side population sorting),marker expression[e.g.,SRY-related HMG-box transcription factor(SOX)2,octamer-binding transcription factor 4,CD133,Nestin],pathway involvement(e.g.,Wnt/betacatenin,Notch,Sonic hedgehog),and functional behaviors such as self-renewal,differentiation,tumorigenicity,and therapy resistance.RESULTS Following duplicate removal,315 unique articles were screened,with 47 full texts assessed for eligibility.Ultimately,34 studies published between 2007 and 2025 met the inclusion criteria.The majority utilized human PitNET samples(83%),with a subset employing rat-derived cell lines(28%)or murine models(15%).PASCs were identified and characterized using various in vitro and in vivo approaches.Commonly reported stemness markers included SOX2(59%),CD133(38%),Nestin(35%),and octamer-binding transcription factor 4(26%),with others such as SOX9,paired-like homeobox 1,and C-X-C chemokine receptor type 4 also frequently cited.Wnt/betacatenin(18%)and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(9%)signaling pathways were most implicated,followed by Notch,Sonic hedgehog,and janus kinase/signal transducer and activator of transcription cascades.Functional assays revealed consistent findings of tumor initiation(44%),selfrenewal(35%),and tumor progression or invasion(35%).Notably,a minority of studies explored therapeutic interventions targeting PASCs,including gamma-secretase inhibitors and possible novel combinations of molecular agents.CONCLUSION The accumulating evidence on PASCs highlights their pivotal role in PitNET tumorigenesis,progression,and therapy resistance.Their molecular and functional overlap with normal pituitary stem cells underscores the need for further lineage-tracing and in vivo validation.展开更多
BACKGROUND Cytomegalovirus(CMV)is a ubiquitous herpesvirus that can cause significant ocular morbidity,particularly in immunocompromised individuals.AIM To summarize the current understanding of the ophthalmic impact ...BACKGROUND Cytomegalovirus(CMV)is a ubiquitous herpesvirus that can cause significant ocular morbidity,particularly in immunocompromised individuals.AIM To summarize the current understanding of the ophthalmic impact of CMV,with a focus on its epidemiology,clinical manifestations,diagnosis,and management,ocular symptoms of CMV floaters,blurred vision,and loss of peripheral vision,eventually progressing to retinal necrosis and detachment.CMV retinitis(CMVR)is a sight-threatening condition that can lead to retinal detachment,blindness,and even death.METHODS We discuss the pathophysiology of CMVR,including the role of immune suppression and viral reactivation.We also examine the clinical features of CMVR,including its characteristic retinal lesions and associated ocular complications.Diagnostic approaches are reviewed,including polymerase chain reaction and fundus photography.RESULTS We discuss treatment options,including antiviral medications,intravitreal injections,and surgical interventions.Finally,we highlight areas of ongoing research and future directions in managing CMV-related ocular disease.CONCLUSION CMV poses a significant threat to ocular health,particularly in immunocompromised populations such as those with human immunodeficiency virus/acquired immune deficiency syndrome.展开更多
The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation...The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown.In this study,we first detected and validated the rich club in the structural networks of mouse,monkey,and human brains using neuronal tracing or diffusion magnetic resonance imaging data.Further,we assessed the role of rich clubs in functional integration,segregation,and balance using quantitative metrics.Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species,with the functional networks of higher species exhibiting greater integration.These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.展开更多
Background:Glioblastoma(GBM)remains themost aggressive primary brain tumour in adults,marked by pronounced cellular heterogeneity,diffuse infiltration,and resistance to conventional treatment.In recent years,transcrip...Background:Glioblastoma(GBM)remains themost aggressive primary brain tumour in adults,marked by pronounced cellular heterogeneity,diffuse infiltration,and resistance to conventional treatment.In recent years,transcriptomic profiling has provided valuable insights into the molecular mechanisms that govern the progression of glioblastoma.This systematic review aims to synthesise the current literature on dysregulated gene expression in GBM,focusing on gene signatures associatedwith stemness,immunemodulation,extracellularmatrix remodelling,metabolic adaptation,and therapeutic resistance.Methods:We conducted a systematic search of PubMed,The Cancer Genome Atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),and the GlioVis portal for studies published between January 2005 and April 2025,limited to English-language reports.Studies were eligible if they included adult glioblastoma tissue or patient-derived datasets and reported gene-level expression or clinical associations.Reviews,commentaries,and studies on non-GBM gliomas were excluded.Screening followed the PRISMA 2020 checklist,with 410 records initially identified,90 duplicates removed,and 125 studies retained after full-text review.Data were synthesised descriptively,and findings were validated against TCGA/CGGA expression datasets to ensure consistency across cohorts.Results:We categorised recurrently dysregulated genes by their biological function,including transcription factors(SOX2,ZEB2),growth factor receptors(EGFR,PDGFRA),immune-related markers(PD-L1,TAP1,B2M),extracellular matrix regulators(MMP2,LAMC1,HAS2),and metabolic genes(SLC7A11,PRMT5,NRF2).For each group,we examine the functional consequences of transcriptional alterations and their role in driving key glioblastoma phenotypes,including angiogenesis,immunosuppression,invasiveness,and recurrence.Conclusion:We further discuss the prognostic implications of these gene signatures and evaluate their potential utility in precisionmedicine,including current clinical trials that target molecular pathways identified through transcriptomic data.This review highlights the power of gene expression profiling to stratify glioblastoma subtypes and improve personalised therapeutic strategies.展开更多
文摘The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).
文摘Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treatment and nursing care have greatly improved the life expectancy of individuals with DS.However,as they age,their risk of developing Alzheimer’s disease(AD)increases considerably(Antonarakis et al.,2020).
文摘Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially mesenchymal stem cells(MSCs),has surfaced as a viable approach for tissue regeneration and immunological regulation in DED.Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality,diminish inflammation,and facilitate corneal regeneration.Nonetheless,obstacles persist in enhancing MSC viability,determining the optimal MSC source,and guaranteeing sustained therapeutic effectiveness.Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.
基金supported by funding from the National Institutes of Health(R01 NS117510)(to RLM)。
文摘Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular networks.Brain vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the brain.This elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing vasculature.Brain capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.
文摘“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.
文摘BACKGROUND Disorders of gut-brain interaction(DGBI)are common,but knowledge about their physiopathology is still poor,nor valid tools have been used to evaluate them in childhood.AIM To develop a psycho-gastroenterological questionnaire(PGQ)to assess the psycho-gastroenterological profile and social characteristics of a pediatric population with and without DGBI.METHODS One hundred and nineteen Italian children(age 11-18)were included:28 outpatient patients with DGBI(Rome IV criteria)and 91 healthy controls.They filled the PGQ,faces pain scale revised(FPS-R),Bristol stool chart,ga-strointestinal symptoms rating scale,state-trait anxiety inventory,Toronto alexithymia scale 20,perceived self-efficacy in the management of negative emotions and expression of positive emotions(APEN-G,APEP-G),irritable bowel syndrome-quality of life questionnaire,school performances,tobacco use,early life events,degree of digital-ization.RESULTS Compared to controls,patients had more medical examinations(35%of them went to the doctor more than five times),a higher school performance(23%vs 13%,P<0.05),didn’t use tobacco(never vs 16%,P<0.05),had early life events(28%vs 1%P<0.05)and a higher percentage of pain classified as 4 in the FPS-R during the examination(14%vs 7%,P<0.05).CONCLUSION Pediatric outpatients with DGBI had a higher prevalence of early life events,a lower quality of life,more medical examinations rising health care costs,lower anxiety levels.
文摘Peyronie's disease(PD)is a challenging condition that significantly impacts male sexual health,often leading to penile curvature,pain,and erectile dysfunction.Treatment options range from conservative pharmacologic approaches to more invasive surgical interventions,with collagenase clostridium histolyticum(CCH)being the only U.S.Food and Drug Administration(FDA)-approved intralesional therapy.However,optimizing treatment strategies to enhance efficacy while minimizing patient burden remains an area of ongoing investigation.^(1,2)
文摘Premenstrual and menstrual exacerbation of psychiatric disorders is a significant area of concern in female mental health.Many females experience a worsening of psychiatric symptoms in the premenstrual and menstrual phases of their menstrual cycle,including heightened anxiety,depression,irritability,and mood swings.These exacerbations are most commonly associated with premenstrual syndrome and premenstrual dysphoric disorder that are characterized by severe emotional and physical symptoms that interfere with daily functioning.The hormonal fluctuations during the menstrual cycle,particularly changes in estrogen and progesterone levels,are believed to play a pivotal role in these exacerbations.Psychiatric disorders such as depression,anxiety,bipolar disorder,and schizophrenia may be influenced by these hormonal changes,with many females reporting an increase in symptom severity during specific phases of the cycle.The mechanisms behind this phenomenon remain complex,with both biological and psychosocial factors contributing to the heightened vulnerability.Clinical management includes careful monitoring of symptom patterns in relation to the menstrual cycle,with treatment options ranging from lifestyle modifications and psychotherapy to pharmacological interventions such as antidepressants and hormonal therapies.Understanding the link between menstruation and psychiatric disorders is essential for improving diagnosis and tailoring effective treatment strategies for affected individuals.
文摘Mourning and grief are natural responses to loss and can be especially complex and prolonged in the context of end-of-life care.Caregivers play a crucial role in supporting individuals through this difficult journey,often balancing their own grief with the need to provide care.This paper explores the experiences of mourning and grief in hospice settings,with a focus on the emotional challenges faced by both patients and caregivers during the grieving process.Psychological support plays a crucial role at the end of life in a multidisciplinary care approach.By addressing the complex interplay between biological disease and psychological well-being,healthcare professionals can provide more comprehensive and compassionate care.A deep understanding of mourning and elaboration of grief would improve the implementation of suitable support interventions and facilitate collaboration among family members and healthcare teams,ultimately improving the quality of end-of-life care and promoting the well-being of both patients and their families.
文摘The gut microbiota plays a pivotal role in human health,influencing diverse physiological processes,including those related to sexual health.Emerging evidence suggests a bidirectional relationship between the gut microbiota and sexual health,mediated by its impact on systemic inflammation,hormonal regulation,and immune function.A balanced gut microbiota supports optimal levels of sex hormones,such as estrogen and testosterone,which are critical for sexual function and reproductive health.Additionally,gut-derived metabolites such as short-chain fatty acids contribute to maintaining mucosal barrier integrity and regulating immune responses,which are essential for protecting against infections that may impair sexual health.Conversely,dysbiosis,an imbalance in gut microbial composition,has been linked to conditions such as erectile dysfunction,polycystic ovary syndrome,and reduced libido,emphasizing its role in sexual dysfunction.Lifestyle factors,including diet,stress,and antibiotic use,can modulate the gut microbiota and,consequently,sexual health outcomes.Recent therapeutic approaches,such as probiotics,prebiotics,and fecal microbiota transplantation,offer potential for restoring gut balance and improving sexual health.This review highlights the central role of the gut microbiota in sexual health,emphasizing its importance as a target for therapeutic interventions to enhance overall well-being.
文摘AIM:To identify optical coherence tomography(OCT)features present at the diagnosis of neovascular age-related macular degeneration(nAMD)that could predict retinal atrophy(RA)and visual performance in patients treated with intravitreal aflibercept.METHODS:OCT data collected at the time of nAMD diagnosis(T0),after the first(T1)and third(T2)intravitreal aflibercept injection,and 5y post-diagnosis(T3)were analyzed.The study included 46 eyes from patients undergoing treatment.The association of OCT features with RA and visual acuity(VA)development over time were evaluated.RESULTS:Patients with RA at T3 exhibited worse VA(35.19±5.7 vs 8.90±2.3,P<0.001)and a lower rate of improvement or stability at T2(90.48%vs 56.00%,P=0.019)and T3(85.71%vs 8.00%,P<0.001).The development of RA at T3 was linked with type 2 macular neovascularization(MNV;4.76%vs 36.00%,P=0.013),thinner outer nuclear layer(ONL,88.89±7.82μm vs 71.38±14.14μm,P=0.033),presence of intraretinal fluid(IRF,42.86%vs 80.00%,P=0.014),presence of IRF without subretinal fluid at T0(SRF,4.76%vs 32.00%,P=0.027),and reduced central foveal thickness at T3(CFT,190.14±22.79μm vs 124.32±14.35μm,P<0.001).The presence of SRF with or without IRF at the diagnosis was comparable between the two groups(90.48%vs 68.00%;P=0.084).CONCLUSION:Type 2 MNV,reduces ONL and CFT,and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients,underscoring the importance of these OCT features in early risk assessment and management strategies.
文摘Pelvic fractures are rare but severe injuries that severely affect patients’quality of life.Treatment of these fractures often involves invasive approaches with high risk of injuries to nervous structures,particularly lumbosacral plexus.The introduction of minimally invasive surgical approaches,such as the lateral rectus approach,not only contributes to preserving lumbar plexus integrity in operated patients but also positively impacts their psychological well-being.Patients treated by surgical reduction of pelvic fractures with lumbosacral plexus injury often experience states of anxiety and depression.The lateral rectus approach is associated with lower levels of anxiety and depression compared to more invasive surgical techniques used for similar fractures.
文摘Dear Editor,Robot-assisted partial nephrectomy(RAPN)has become the preferred surgical treatment for most renal tumors[1].Local recurrences occur in 1%-10% of patients undergoing partial nephrectomy,and they tend to appear within the first 5 years after surgery[2].
基金approved by the Institutional Review Board of Università Cattolica del Sacro Cuore-Policlinico Gemelli IRCCS(number DIPUSVSP-21-03-252).
文摘Background:Adult medulloblastoma(MB)represents less than 1%of central nervous system malignancies,lacking standardized therapeutic approaches due to its rarity.This retrospective single-center analysis aimed to assess survival outcomes and treatment-associated toxicities in adult MB patients managed with pediatric-derived protocols.Methods:Eighteen patients(≥18 years)with MB treated at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)(January 1997–January 2024)were analyzed.All received craniospinal radiotherapy with posterior fossa boost,followed by adjuvant chemotherapy utilizing pediatric regimens(PNET3,PNET4,PNET5,or high-risk protocols incorporating high-dose chemotherapy with autologous stem cell rescue).Primary outcomes included overall survival(OS)and progression-free survival(PFS).Secondary analyses focused on comprehensive toxicity assessment.Results:The cohort included 11 males and 7 females(median age:23 years).Metastatic disease was present in 6 patients(33%)at diagnosis.Histopathological distribution showed classic MB(55.5%),desmoplastic/nodular(39%),and large cell/anaplastic variants(5.5%).Molecular subgrouping(available in 6 patients)identified SHH subgroup in four cases and WNT subgroup in two.Three-year and fiveyear overall survival rates reached 94.5%and 88.8%,respectively.Treatment-related adverse events included grade 3–4 hematologic toxicities,clinically significant weight loss,and grade≥3 neurological and ototoxic complications.These toxicities necessitated treatment modifications including dose adjustments,cycle delays,and occasional early discontinuation.Conclusions:Adult MB patients treated with pediatric-adapted protocols demonstrated excellent long-termsurvival outcomes,comparable to or surpassing historical data.Despite frequent toxicity requiring treatment modifications,these regimens proved feasible with acceptable risk-benefit profiles.These results support implementing modified pediatric protocols for adult MB management.Future multicenter investigations with larger cohorts are essential for refining risk stratification,optimizing treatment intensity,and evaluating long-term outcomes in this rare malignancy.
文摘Objective:Pelvic organ-sparing surgery aims to preserve vital reproductive and sexual organs,enhancing quality of life,especially in premenopausal women.Pelvic organ preservation for female patients undergoing radical cystectomy is now emphasized for sexual and hormonal function.Recent screening studies show no survival advantage despite early diagnosis of ovarian cancer,but opportunistic salpingectomy could reduce high-grade serous carcinoma risk.The aim of this review was to analyze the incidence of metachronous or delayed ovarian cancer in patients undergoing radical cystectomy for bladder cancer.Methods:PubMed,Scopus,Web of Science,ClinicalTrials.gov,and Cochrane Library were searched systematically for English-language articles up to June 2024.The selection was done first by title and abstract screening and then by full-text assessment for eligibility.This review has been registered in PROSPERO(CRD42024561902).Results:This review included two retrospective studies(2211 patients).Most patients had local or regional advanced disease,with a minority having distant disease.Only one study reported direct pelvic organ involvement from urothelial cancer,with no ovarian involvement found.Among patients who had organ-sparing surgery or pelvic exenteration,only two developed ovarian cancer post-surgery.No mean follow-up time or side effects from pelvic organ removal were reported in either study.Conclusion:When oncologically safe,ovarian-sparing surgery with salpingectomy should be considered in female bladder cancer patients undergoing radical cystectomy.Opportunistic salpingectomy should be encouraged during abdominal urological surgeries,with thorough preoperative counseling guiding decisions.Further studies are needed to define the role of preventive gynecologic surgery in urologic procedures.
文摘BACKGROUND Pituitary neuroendocrine tumors(PitNETs),formerly referred to as pituitary adenomas,are prevalent intracranial neoplasms that,although often benign histologically,can demonstrate invasive growth,therapeutic resistance,and recurrence.Emerging evidence supports the presence of a subpopulation of tumorinitiating cells with stem-like properties-pituitary adenoma stem cells(PASCs)-that may drive these aggressive features.This systematic review aims to critically examine the evidence on PASCs,their phenotypic and functional characteristics,and their role in PitNET pathophysiology.AIM To study the molecular markers,signaling pathways,research models,and phenotypic traits of PASCs,and to assess their potential significance for future translational and clinical applications.METHODS A comprehensive literature search was conducted in PubMed,Scopus,and Ovid MEDLINE in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Thirty-four studies were included based on predefined eligibility criteria.Data were extracted regarding PASC isolation methods(e.g.,neurosphere formation,side population sorting),marker expression[e.g.,SRY-related HMG-box transcription factor(SOX)2,octamer-binding transcription factor 4,CD133,Nestin],pathway involvement(e.g.,Wnt/betacatenin,Notch,Sonic hedgehog),and functional behaviors such as self-renewal,differentiation,tumorigenicity,and therapy resistance.RESULTS Following duplicate removal,315 unique articles were screened,with 47 full texts assessed for eligibility.Ultimately,34 studies published between 2007 and 2025 met the inclusion criteria.The majority utilized human PitNET samples(83%),with a subset employing rat-derived cell lines(28%)or murine models(15%).PASCs were identified and characterized using various in vitro and in vivo approaches.Commonly reported stemness markers included SOX2(59%),CD133(38%),Nestin(35%),and octamer-binding transcription factor 4(26%),with others such as SOX9,paired-like homeobox 1,and C-X-C chemokine receptor type 4 also frequently cited.Wnt/betacatenin(18%)and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(9%)signaling pathways were most implicated,followed by Notch,Sonic hedgehog,and janus kinase/signal transducer and activator of transcription cascades.Functional assays revealed consistent findings of tumor initiation(44%),selfrenewal(35%),and tumor progression or invasion(35%).Notably,a minority of studies explored therapeutic interventions targeting PASCs,including gamma-secretase inhibitors and possible novel combinations of molecular agents.CONCLUSION The accumulating evidence on PASCs highlights their pivotal role in PitNET tumorigenesis,progression,and therapy resistance.Their molecular and functional overlap with normal pituitary stem cells underscores the need for further lineage-tracing and in vivo validation.
文摘BACKGROUND Cytomegalovirus(CMV)is a ubiquitous herpesvirus that can cause significant ocular morbidity,particularly in immunocompromised individuals.AIM To summarize the current understanding of the ophthalmic impact of CMV,with a focus on its epidemiology,clinical manifestations,diagnosis,and management,ocular symptoms of CMV floaters,blurred vision,and loss of peripheral vision,eventually progressing to retinal necrosis and detachment.CMV retinitis(CMVR)is a sight-threatening condition that can lead to retinal detachment,blindness,and even death.METHODS We discuss the pathophysiology of CMVR,including the role of immune suppression and viral reactivation.We also examine the clinical features of CMVR,including its characteristic retinal lesions and associated ocular complications.Diagnostic approaches are reviewed,including polymerase chain reaction and fundus photography.RESULTS We discuss treatment options,including antiviral medications,intravitreal injections,and surgical interventions.Finally,we highlight areas of ongoing research and future directions in managing CMV-related ocular disease.CONCLUSION CMV poses a significant threat to ocular health,particularly in immunocompromised populations such as those with human immunodeficiency virus/acquired immune deficiency syndrome.
基金supported by STI2030-Major Projects(2021ZD0200200)the National Natural Science Foundation of China(62327805 and 82151307)+1 种基金the Equipment Development Project of the Chinese Academy of Sciences(YJKYYQ20190040)the Science and Technology Innovation Program of Hunan Province(2024RC4028).
文摘The rich club,as a community of highly interconnected nodes,serves as the topological center of the network.However,the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown.In this study,we first detected and validated the rich club in the structural networks of mouse,monkey,and human brains using neuronal tracing or diffusion magnetic resonance imaging data.Further,we assessed the role of rich clubs in functional integration,segregation,and balance using quantitative metrics.Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species,with the functional networks of higher species exhibiting greater integration.These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
文摘Background:Glioblastoma(GBM)remains themost aggressive primary brain tumour in adults,marked by pronounced cellular heterogeneity,diffuse infiltration,and resistance to conventional treatment.In recent years,transcriptomic profiling has provided valuable insights into the molecular mechanisms that govern the progression of glioblastoma.This systematic review aims to synthesise the current literature on dysregulated gene expression in GBM,focusing on gene signatures associatedwith stemness,immunemodulation,extracellularmatrix remodelling,metabolic adaptation,and therapeutic resistance.Methods:We conducted a systematic search of PubMed,The Cancer Genome Atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),and the GlioVis portal for studies published between January 2005 and April 2025,limited to English-language reports.Studies were eligible if they included adult glioblastoma tissue or patient-derived datasets and reported gene-level expression or clinical associations.Reviews,commentaries,and studies on non-GBM gliomas were excluded.Screening followed the PRISMA 2020 checklist,with 410 records initially identified,90 duplicates removed,and 125 studies retained after full-text review.Data were synthesised descriptively,and findings were validated against TCGA/CGGA expression datasets to ensure consistency across cohorts.Results:We categorised recurrently dysregulated genes by their biological function,including transcription factors(SOX2,ZEB2),growth factor receptors(EGFR,PDGFRA),immune-related markers(PD-L1,TAP1,B2M),extracellular matrix regulators(MMP2,LAMC1,HAS2),and metabolic genes(SLC7A11,PRMT5,NRF2).For each group,we examine the functional consequences of transcriptional alterations and their role in driving key glioblastoma phenotypes,including angiogenesis,immunosuppression,invasiveness,and recurrence.Conclusion:We further discuss the prognostic implications of these gene signatures and evaluate their potential utility in precisionmedicine,including current clinical trials that target molecular pathways identified through transcriptomic data.This review highlights the power of gene expression profiling to stratify glioblastoma subtypes and improve personalised therapeutic strategies.
