Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations ...Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system,liver enzyme abnormalities exist in around half of the cases,which indicate liver injury,and raise clinical concern.At present,there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response.This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARSCoV-2 infection.展开更多
Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, a...Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, apoptosis, adhesion, immune evasion, etc. （1）] are considered to be the two central driving pathogenic features in the progression of clear cell Renal Cell Carcinoma （ccRCC） （2,3）.展开更多
Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophy...Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophysiological processes in which heat triggers a cascade of dysregulated inflammatory responses,endothelial dysfunction,coagulation abnormalities,and muscle damage.These processes can lead to multiorgan failure,significantly increasing the risk of mortality.^([2])Given the severity of EHS,early identification and timely intervention are crucial.However,there are no specific diagnostic markers for EHS,^([1])highlighting the need to identify reliable clinical parameters that can assist early decision-making.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
The rapid expansion of urbanization has led to widespread exposure of wild birds to intensive light at night(LAN).While previous studies have established LAN-induced cognitive impairment in birds,the underlying neurob...The rapid expansion of urbanization has led to widespread exposure of wild birds to intensive light at night(LAN).While previous studies have established LAN-induced cognitive impairment in birds,the underlying neurobiological mechanisms remain poorly understood.We hypothesized that LAN exposure impaired cognitive function of birds potentially through neurodegeneration,metabolic dysregulation and neuroinflammatory responses in the telencephalon.Using Zebra Finches(Taeniopygia guttata)as an avian model,under 16L:8D photoperiods,we compared associative learning and memory abilities and neurobiological parameters between experimental groups exposed to dim light at night(LAN)versus nocturnal darkness(CTR).Compared to the CTR birds,the LAN-exposed birds exhibited significantly lower learning and memory performances,reduced neuron density and simplified dendritic morphology in the telencephalons.The key energy metabolic substrates(cholic acid,CTP,D-mannose-6-phosphate)and neuroprotective agents(trehalose,menaquinone,L-gulono-1,4-lactone)in the telencephalons of LAN-exposed birds showed depletion,while oxidative stress markers(methionine sulfoxide)and inflammatory mediators(cis-gondoic acid)exhibited elevation.The neurotransmitter dopamine and histamine metabolic pathway were disrupted in the LAN-exposed birds.The microglias were activated with pro-inflammatory IL-1βand IL-6 levels increasing and anti-inflammatory IL-10 decreasing in the telencephalons of the LAN-exposed birds.These findings indicate a potential mechanistic pathway whereby dim light exposure at night can induce neuroinflammation through oxidative stress-mediated microglial activation,energy metabolism and neurotransmitter homeostasis disruption,ultimately leading to neurodegeneration in the telencephalons of birds.展开更多
BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations.This manuscript explores the multidisciplinary appro...BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations.This manuscript explores the multidisciplinary approach to understanding and managing pituitary macroadenomas,integrating neurosurgery,endocrinology,radiology,and pathology perspectives.AIM To summarize the literature on pituitary macroadenoma and outline the possible multidisciplinary approach in the diagnosis,management,and rehabilitation of individuals with pituitary adenomas,to add to already preexisting knowledge,in managing these cases enhancing better ocular and systemic outcomes.METHODS A search was conducted on an online publication database(PubMed)using the term“pituitary adenoma”including all results published over twenty years(2004-2024).Results were sorted for relevance,language,and completeness.RESULTS A total of 176 records were returned.The guidelines of the PRISMA 2020 statement were followed in this study.A total of 23 records were excluded due to being out of scope while a further 13 records were duplicates.Another 17 records were not available as full-length articles and were also excluded.The references of each included record was further searched for relevant publications.A total of 141 records were therefore used in this minireview.CONCLUSION Pituitary macroadenomas pose substantial clinical challenges due to their size and potential for significant hormonal and neurological impact,modern therapeutic strategies offer effective management options.Early detection and comprehensive treatment are essential for optimizing patient outcomes and maintaining quality of life.Continued research and advancements in medical technology are likely to further enhance the management and prognosis of this condition in the future.展开更多
Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in de...Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in developing various endoderm-derived organs.Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.Dysregulation of FOXR2 has been linked to numerous malignant tumors,spanning the brain,nervous system,thyroid,osteosarcoma,Hodgkin lymphoma,colorectal,liver,pancreatic,lung,breast,ovarian,prostate,female genital tract,endometrial,and uterine cancers.Despite extensive research on FOXR2 dysregulation,its practical applications remain underexplored.This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis,prognosis,and treatment.展开更多
Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher ...Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher prevalence of carotid atherosclerosis in patients with chronic hepatitis C infection,with viral load and steatosis emerging as independent risk factors.HCV-related athero-sclerosis appears to develop through complex processes involving endothelial dysfunction,inflammation,oxidative stress,and immune dysregulation.Key cytokines,including tumor necrosis factor-alpha and interleukin-6,increase inflammatory responses,while oxidative stress markers,such as malondial-dehyde,are associated with an increased risk of atherogenesis.In addition,HCV infection has been linked to cardiomyopathy.Direct viral effects,including HCV replication within cardiomyocytes and cytotoxicity induced by viral proteins,lead to myocardial injury and functional decline.Indirectly,HCV triggers immune-mediated damage,with heightened pro-inflammatory cytokines exacerbating cardiomyocyte apoptosis and fibrosis.Furthermore,HCV infection promotes a procoagulant imbalance,as evidenced by elevated factor VIII levels and thrombin potential,contributing to the increased cardiovascular risk.While substantial evidence indicates a relationship between HCV and cardiovascular disease,further research is needed to establish causality and guide therapeutic interventions.展开更多
Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working...Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.展开更多
Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and...Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.展开更多
With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely o...With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely obesity and neurodegeneration.展开更多
Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs freq...Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs frequently coexist with liver diseases,including cirrhosis,thereby exacerbating clinical manifestations and complicating management;this overlap is underpinned by shared mechanisms,including gut dysbiosis,increased intestinal permeability,systemic inflammation,and altered neuroimmune signaling.Portal hypertension in cirrhosis promotes small intestinal bacterial overgrowth and microbial translocation,thereby triggering inflammatory pathways that worsen gut and liver function.This minireview explores the gut-liver axis as a central mediator in the interplay between DGBIs and liver disease/cirrhosis.Clinically,these interactions manifest as refractory gastrointestinal symptoms,nutritional deficiencies,and impaired quality of life.Emerging research emphasizes the need for integrative diagnostic approaches,such as combining advanced imaging,microbiome analysis,and biomarker profiling,to unravel the complex interplay between DGBIs and liver disease/cirrhosis.Therapeutic interventions targeting the gut microbiome,neuroimmune pathways,and lifestyle modification can mitigate disease burden.This review underscores the importance of a multidisciplinary framework for enhancing patient outcomes and guiding future research in this intersectional field.展开更多
Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Ret...Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral...BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.展开更多
Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.T...Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.This study integrated proteomics and cytokine array approach to identify the multifactorial and multicellular interaction effects driving liver fibrosis in dairy cows with ketosis and analyze the mechanism by which the proinflammatory shift in macrophages contributes to liver fibrosis.Results Histopathological analysis revealed liver injury,including severe steatosis,infiltration of inflammatory cells,an increase in lipid deposition,and a decrease in glycogen expression in ketotic cows.Moreover,the number of mitochondria considerably increased in hepatocytes.The activation of the dynamin-related protein 1/mitochondrial fission factor(DRP1/MFF)pathway induced excessive mitochondrial fission,and the inhibition of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1(Nrf2/HO-1)pathway led to the accumulation of intracellular reactive oxygen species(ROS).Proteomic analysis revealed the activation of extracellular matrix(ECM)-related functions and the NF-κB pathway in the liver,whereas cytokine array analysis revealed that the cytokine network was dysregulated.The accumulation of ROS triggered NF-κB nuclear translocation,inducing a proinflammatory shift in macrophages and liver inflammation.M1 polarization of macrophages promotes the release of proinflammatory mediators,which stimulated hepatic stellate cells(HSCs)activation,leading to ECM deposition,ultimately contributing to liver fibrosis.Conclusions To summarize,our study revealed the multifactorial and multicellular interaction effects driving liver fibrosis.Our results preliminarily showed that increased mitochondrial fission and inhibition of the Nrf2/HO-1 pathway are key factors in activating macrophages,which can lead to liver fibrosis in dairy cows with ketosis.展开更多
Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metaboli...Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metabolism dysregu-lation in DOP pathogenesis,focusing on ferroptosis,a novel iron-dependent cell death pathway characterized by lipid peroxidation and reactive oxygen species(ROS)overproduction.Diabetic conditions exacerbate iron overload,impairing osteoblast function and enhancing osteoclast activity,while triggering ferroptosis in bone cells.Ferroptosis not only accelerates osteoblast apoptosis but also amplifies osteoclast-mediated bone resorption,synergistically promoting bone loss.Furthermore,chronic inflammation and oxidative stress disrupt the balance between bone formation and resorption,with elevated pro-inflammatory cyto-kines(e.g.,tumor necrosis factor-α,interleukin-6)and ROS exacerbating cellular dysfunction.Therapeutic strategies targeting iron metabolism(e.g.,deferoxamine)and ferroptosis inhibition(e.g.,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway activation,antioxidants like melatonin)demonstrate potential to mitigate DOP progression.Future research should prioritize personalized interventions,clinical trials of iron chelators and antioxidants,and mechanistic studies to refine therapeutic approaches.This review provides a comprehensive framework for understanding DOP pathogenesis and highlights innovative strategies to improve bone health in diabetic patients.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is increasingly recognized for its role in the pathogenesis of various cancers.However,its impact on gastric cancer(GC)outcomes,particularly in patients undergoing la...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is increasingly recognized for its role in the pathogenesis of various cancers.However,its impact on gastric cancer(GC)outcomes,particularly in patients undergoing laparoscopic distal gastrectomy(LDG),remains unclear.AIM To investigate the clinical and prognostic impacts of NAFLD on GC patients undergoing LDG.METHODS In this retrospective cohort study,we collected clinical data from 1122 GC patients who underwent LDG at the Gastric Cancer Center of the First Affiliated Hospital of Nanjing Medical University between January 2020 and December 2022.Propensity score-matching(PSM)was used to mitigate the bias to compare the oncological and surgical outcomes between the two groups.Survival analysis was also performed to evaluate NAFLD as a prognostic factor.RESULTS PSM yielded a balanced cohort of 260 patients(52 with NAFLD and 208 controls)from the original cohort.No differences in clinicopathological characteristics,including surgery time,complications,T stage,N stage,p-tumornode-metastasis stage,neural invasion,vascular invasion,total number of retrieved lymph nodes,positive retrieved lymph nodes and positive lymph nodes rate,were observed between the two groups.Overall survival was comparable between two groups(Log-rank P=0.49),whereas progression-free survival(PFS)in the NAFLD group was inferior to that in the control group(Log-rank P=0.016).Univariable Cox regression analysis further confirmed that NAFLD was an unfavorable prognostic factor for PFS.CONCLUSION GC patients with NAFLD exhibited inferior PFS,suggesting that addressing NAFLD-related metabolic alterations may enhance clinical outcomes.Future investigations should explore the mechanistic links between NAFLD and GC progression and consider integrated therapeutic strategies.展开更多
Sleep disorders,particularly insomnia,have emerged as a critical public health challenge,with the situation worsened by the coronavirus disease-2019 pandemic.Insomnia symptoms,which affected up to 45%of the population...Sleep disorders,particularly insomnia,have emerged as a critical public health challenge,with the situation worsened by the coronavirus disease-2019 pandemic.Insomnia symptoms,which affected up to 45%of the population during this period,highlight the urgent need to understand the mechanisms linking sleep disturbances to mental health outcomes.Recent findings suggest that cognitive failures,such as memory lapses and attentional deficits,mediate the relationship between insomnia and emotional disorders such as anxiety and depression.The role of personality traits,particularly neuroticism,adds further complexity,as it may either exacerbate or buffer these effects under specific conditions.This review explores the study by Li et al,which offers valuable insights into the cognitive-emotional pathways influenced by sleep disturbances.The study makes significant contributions by identifying key cognitive mechanisms and proposing the dual role of neuroticism in shaping emotional outcomes.To advance these findings,this letter advocates for future longitudinal research and the integration of targeted interventions,such as cognitive-behavioral therapy for insomnia,into public health frameworks.By addressing insomnia-induced cognitive dysfunction,these strategies can enhance emotional regulation and foster resilience,particularly in vulnerable populations facing the mental health impacts of the pandemic.展开更多
To the editor:Non-suicidal self-injury(NSSI)is an array of directly prepense or repetitive self-harm behaviours without suicidal intent.Individuals engage in self-injurious behaviours to reduce negative mental and cog...To the editor:Non-suicidal self-injury(NSSI)is an array of directly prepense or repetitive self-harm behaviours without suicidal intent.Individuals engage in self-injurious behaviours to reduce negative mental and cognitive states or evoke positive emotions.展开更多
基金Supported by Sino-German Center for Research Promotion,National Natural Science Foundation of China,No.C-0029Health Commission of Chengdu,No.2020179.
文摘Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system,liver enzyme abnormalities exist in around half of the cases,which indicate liver injury,and raise clinical concern.At present,there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response.This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARSCoV-2 infection.
文摘Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, apoptosis, adhesion, immune evasion, etc. （1）] are considered to be the two central driving pathogenic features in the progression of clear cell Renal Cell Carcinoma （ccRCC） （2,3）.
基金funded by Research Fund of Zhejiang Provincial Health Commission (2025KY8662025)。
文摘Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophysiological processes in which heat triggers a cascade of dysregulated inflammatory responses,endothelial dysfunction,coagulation abnormalities,and muscle damage.These processes can lead to multiorgan failure,significantly increasing the risk of mortality.^([2])Given the severity of EHS,early identification and timely intervention are crucial.However,there are no specific diagnostic markers for EHS,^([1])highlighting the need to identify reliable clinical parameters that can assist early decision-making.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
基金supported by grants from Key laboratory of Ecology and Environment in Minority Area,National Ethnic Affairs Commission(KLEEMA202207)。
文摘The rapid expansion of urbanization has led to widespread exposure of wild birds to intensive light at night(LAN).While previous studies have established LAN-induced cognitive impairment in birds,the underlying neurobiological mechanisms remain poorly understood.We hypothesized that LAN exposure impaired cognitive function of birds potentially through neurodegeneration,metabolic dysregulation and neuroinflammatory responses in the telencephalon.Using Zebra Finches(Taeniopygia guttata)as an avian model,under 16L:8D photoperiods,we compared associative learning and memory abilities and neurobiological parameters between experimental groups exposed to dim light at night(LAN)versus nocturnal darkness(CTR).Compared to the CTR birds,the LAN-exposed birds exhibited significantly lower learning and memory performances,reduced neuron density and simplified dendritic morphology in the telencephalons.The key energy metabolic substrates(cholic acid,CTP,D-mannose-6-phosphate)and neuroprotective agents(trehalose,menaquinone,L-gulono-1,4-lactone)in the telencephalons of LAN-exposed birds showed depletion,while oxidative stress markers(methionine sulfoxide)and inflammatory mediators(cis-gondoic acid)exhibited elevation.The neurotransmitter dopamine and histamine metabolic pathway were disrupted in the LAN-exposed birds.The microglias were activated with pro-inflammatory IL-1βand IL-6 levels increasing and anti-inflammatory IL-10 decreasing in the telencephalons of the LAN-exposed birds.These findings indicate a potential mechanistic pathway whereby dim light exposure at night can induce neuroinflammation through oxidative stress-mediated microglial activation,energy metabolism and neurotransmitter homeostasis disruption,ultimately leading to neurodegeneration in the telencephalons of birds.
文摘BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations.This manuscript explores the multidisciplinary approach to understanding and managing pituitary macroadenomas,integrating neurosurgery,endocrinology,radiology,and pathology perspectives.AIM To summarize the literature on pituitary macroadenoma and outline the possible multidisciplinary approach in the diagnosis,management,and rehabilitation of individuals with pituitary adenomas,to add to already preexisting knowledge,in managing these cases enhancing better ocular and systemic outcomes.METHODS A search was conducted on an online publication database(PubMed)using the term“pituitary adenoma”including all results published over twenty years(2004-2024).Results were sorted for relevance,language,and completeness.RESULTS A total of 176 records were returned.The guidelines of the PRISMA 2020 statement were followed in this study.A total of 23 records were excluded due to being out of scope while a further 13 records were duplicates.Another 17 records were not available as full-length articles and were also excluded.The references of each included record was further searched for relevant publications.A total of 141 records were therefore used in this minireview.CONCLUSION Pituitary macroadenomas pose substantial clinical challenges due to their size and potential for significant hormonal and neurological impact,modern therapeutic strategies offer effective management options.Early detection and comprehensive treatment are essential for optimizing patient outcomes and maintaining quality of life.Continued research and advancements in medical technology are likely to further enhance the management and prognosis of this condition in the future.
文摘Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in developing various endoderm-derived organs.Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.Dysregulation of FOXR2 has been linked to numerous malignant tumors,spanning the brain,nervous system,thyroid,osteosarcoma,Hodgkin lymphoma,colorectal,liver,pancreatic,lung,breast,ovarian,prostate,female genital tract,endometrial,and uterine cancers.Despite extensive research on FOXR2 dysregulation,its practical applications remain underexplored.This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis,prognosis,and treatment.
文摘Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher prevalence of carotid atherosclerosis in patients with chronic hepatitis C infection,with viral load and steatosis emerging as independent risk factors.HCV-related athero-sclerosis appears to develop through complex processes involving endothelial dysfunction,inflammation,oxidative stress,and immune dysregulation.Key cytokines,including tumor necrosis factor-alpha and interleukin-6,increase inflammatory responses,while oxidative stress markers,such as malondial-dehyde,are associated with an increased risk of atherogenesis.In addition,HCV infection has been linked to cardiomyopathy.Direct viral effects,including HCV replication within cardiomyocytes and cytotoxicity induced by viral proteins,lead to myocardial injury and functional decline.Indirectly,HCV triggers immune-mediated damage,with heightened pro-inflammatory cytokines exacerbating cardiomyocyte apoptosis and fibrosis.Furthermore,HCV infection promotes a procoagulant imbalance,as evidenced by elevated factor VIII levels and thrombin potential,contributing to the increased cardiovascular risk.While substantial evidence indicates a relationship between HCV and cardiovascular disease,further research is needed to establish causality and guide therapeutic interventions.
文摘Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.
文摘Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.
文摘With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely obesity and neurodegeneration.
文摘Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs frequently coexist with liver diseases,including cirrhosis,thereby exacerbating clinical manifestations and complicating management;this overlap is underpinned by shared mechanisms,including gut dysbiosis,increased intestinal permeability,systemic inflammation,and altered neuroimmune signaling.Portal hypertension in cirrhosis promotes small intestinal bacterial overgrowth and microbial translocation,thereby triggering inflammatory pathways that worsen gut and liver function.This minireview explores the gut-liver axis as a central mediator in the interplay between DGBIs and liver disease/cirrhosis.Clinically,these interactions manifest as refractory gastrointestinal symptoms,nutritional deficiencies,and impaired quality of life.Emerging research emphasizes the need for integrative diagnostic approaches,such as combining advanced imaging,microbiome analysis,and biomarker profiling,to unravel the complex interplay between DGBIs and liver disease/cirrhosis.Therapeutic interventions targeting the gut microbiome,neuroimmune pathways,and lifestyle modification can mitigate disease burden.This review underscores the importance of a multidisciplinary framework for enhancing patient outcomes and guiding future research in this intersectional field.
文摘Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.
文摘BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.
基金supported by the National Natural Science Foundation of China(32125038 and 32402957)China National Postdoctoral Program for Innovative Talents(BX20240417)+1 种基金China Postdoctoral Science Foundation funded project(2024M753563)National Key Research and Development Program of China(2023YFD1801100).
文摘Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.This study integrated proteomics and cytokine array approach to identify the multifactorial and multicellular interaction effects driving liver fibrosis in dairy cows with ketosis and analyze the mechanism by which the proinflammatory shift in macrophages contributes to liver fibrosis.Results Histopathological analysis revealed liver injury,including severe steatosis,infiltration of inflammatory cells,an increase in lipid deposition,and a decrease in glycogen expression in ketotic cows.Moreover,the number of mitochondria considerably increased in hepatocytes.The activation of the dynamin-related protein 1/mitochondrial fission factor(DRP1/MFF)pathway induced excessive mitochondrial fission,and the inhibition of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1(Nrf2/HO-1)pathway led to the accumulation of intracellular reactive oxygen species(ROS).Proteomic analysis revealed the activation of extracellular matrix(ECM)-related functions and the NF-κB pathway in the liver,whereas cytokine array analysis revealed that the cytokine network was dysregulated.The accumulation of ROS triggered NF-κB nuclear translocation,inducing a proinflammatory shift in macrophages and liver inflammation.M1 polarization of macrophages promotes the release of proinflammatory mediators,which stimulated hepatic stellate cells(HSCs)activation,leading to ECM deposition,ultimately contributing to liver fibrosis.Conclusions To summarize,our study revealed the multifactorial and multicellular interaction effects driving liver fibrosis.Our results preliminarily showed that increased mitochondrial fission and inhibition of the Nrf2/HO-1 pathway are key factors in activating macrophages,which can lead to liver fibrosis in dairy cows with ketosis.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metabolism dysregu-lation in DOP pathogenesis,focusing on ferroptosis,a novel iron-dependent cell death pathway characterized by lipid peroxidation and reactive oxygen species(ROS)overproduction.Diabetic conditions exacerbate iron overload,impairing osteoblast function and enhancing osteoclast activity,while triggering ferroptosis in bone cells.Ferroptosis not only accelerates osteoblast apoptosis but also amplifies osteoclast-mediated bone resorption,synergistically promoting bone loss.Furthermore,chronic inflammation and oxidative stress disrupt the balance between bone formation and resorption,with elevated pro-inflammatory cyto-kines(e.g.,tumor necrosis factor-α,interleukin-6)and ROS exacerbating cellular dysfunction.Therapeutic strategies targeting iron metabolism(e.g.,deferoxamine)and ferroptosis inhibition(e.g.,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway activation,antioxidants like melatonin)demonstrate potential to mitigate DOP progression.Future research should prioritize personalized interventions,clinical trials of iron chelators and antioxidants,and mechanistic studies to refine therapeutic approaches.This review provides a comprehensive framework for understanding DOP pathogenesis and highlights innovative strategies to improve bone health in diabetic patients.
基金supported by the National Natural Science Foundation of China(No.82300114)the Natural Science Foundation of Hubei Province General Program(No.2023AFB684)the Natural Science Foundation of Hubei Province Youth Program(No.2022CFB671).
文摘Objective Sepsis-induced acute lung injury(ALI)poses a critical challenge in critical care,yet its immunoregulatory mechanisms remain poorly defined.This study aimed to delineate immune dysregulation networks and identify therapeutic targets through multiomics data integration.Methods Transcriptomic datasets(GSE40180 and GSE165226)were analyzed through a multiphase bioinformatics workflow,including gene set enrichment analysis(GSEA),immune cell deconvolution(CIBERSORT),differential gene expression profiling(|log2FC|>1.5,P.adj<0.05),and pathway annotation(GO/KEGG).Protein–protein interaction(PPI)networks were constructed to identify hub genes.Experimental validation was done using a murine cecal ligation and puncture(CLP)model with histopathological lung injury scoring and RT-qPCR-based hub gene verification.Results Integrated analysis revealed 26 consensus biological processes(24 upregulated,2 downregulated)dominated by innate immune activation.CIBERSORT revealed significant infiltration of M1 macrophages,neutrophils,activated dendritic cells(DCs),and activated natural killer(NK)cells in septic lungs,which was concurrent with Th17/naive CD8+T-cell dysregulation.Among the 58 differentially expressed genes(DEG),7 hub genes(Cxcl1,Cxcl2,Ccl3,Cd14,Saa3,Timp1,and Socs3)were significantly correlated with immune cell dynamics.CLP modeling confirmed severe alveolar damage(lung injury score:8.11±1.17 vs.1.97±0.29;P<0.0001)and upregulated hub gene expression(all P<0.01)in septic lungs,with hub gene expression levels strongly correlated with the lung injury score(Pearson’s r>0.85,P<0.001).Conclusion Innate adaptive immune crosstalk,particularly dysregulated immune cell infiltration,drives sepsis-induced ALI pathogenesis.The 7 hub genes mechanistically connect immune dyshomeostasis to tissue injury,suggesting novel targets for precision immunomodulation and biomarker development in critical care.
基金Supported by China Postdoctoral Science Foundation,No.2021TQ0132The Youth Fund Program for National Natural Science Foundation of China from the First Affiliated Hospital of Nanjing Medical University,No.PY2021032。
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is increasingly recognized for its role in the pathogenesis of various cancers.However,its impact on gastric cancer(GC)outcomes,particularly in patients undergoing laparoscopic distal gastrectomy(LDG),remains unclear.AIM To investigate the clinical and prognostic impacts of NAFLD on GC patients undergoing LDG.METHODS In this retrospective cohort study,we collected clinical data from 1122 GC patients who underwent LDG at the Gastric Cancer Center of the First Affiliated Hospital of Nanjing Medical University between January 2020 and December 2022.Propensity score-matching(PSM)was used to mitigate the bias to compare the oncological and surgical outcomes between the two groups.Survival analysis was also performed to evaluate NAFLD as a prognostic factor.RESULTS PSM yielded a balanced cohort of 260 patients(52 with NAFLD and 208 controls)from the original cohort.No differences in clinicopathological characteristics,including surgery time,complications,T stage,N stage,p-tumornode-metastasis stage,neural invasion,vascular invasion,total number of retrieved lymph nodes,positive retrieved lymph nodes and positive lymph nodes rate,were observed between the two groups.Overall survival was comparable between two groups(Log-rank P=0.49),whereas progression-free survival(PFS)in the NAFLD group was inferior to that in the control group(Log-rank P=0.016).Univariable Cox regression analysis further confirmed that NAFLD was an unfavorable prognostic factor for PFS.CONCLUSION GC patients with NAFLD exhibited inferior PFS,suggesting that addressing NAFLD-related metabolic alterations may enhance clinical outcomes.Future investigations should explore the mechanistic links between NAFLD and GC progression and consider integrated therapeutic strategies.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.NRF-RS-2023-00237287.
文摘Sleep disorders,particularly insomnia,have emerged as a critical public health challenge,with the situation worsened by the coronavirus disease-2019 pandemic.Insomnia symptoms,which affected up to 45%of the population during this period,highlight the urgent need to understand the mechanisms linking sleep disturbances to mental health outcomes.Recent findings suggest that cognitive failures,such as memory lapses and attentional deficits,mediate the relationship between insomnia and emotional disorders such as anxiety and depression.The role of personality traits,particularly neuroticism,adds further complexity,as it may either exacerbate or buffer these effects under specific conditions.This review explores the study by Li et al,which offers valuable insights into the cognitive-emotional pathways influenced by sleep disturbances.The study makes significant contributions by identifying key cognitive mechanisms and proposing the dual role of neuroticism in shaping emotional outcomes.To advance these findings,this letter advocates for future longitudinal research and the integration of targeted interventions,such as cognitive-behavioral therapy for insomnia,into public health frameworks.By addressing insomnia-induced cognitive dysfunction,these strategies can enhance emotional regulation and foster resilience,particularly in vulnerable populations facing the mental health impacts of the pandemic.
基金the Innovation 2030-Major Project of Brain Science and Brain-lnspired Intelligence Technology(2021ZD0200600)Shanghai Science and Technology Committee(22YF1439100,YDZX20213100001003)National Natural Science Foundation of China(82201678).
文摘To the editor:Non-suicidal self-injury(NSSI)is an array of directly prepense or repetitive self-harm behaviours without suicidal intent.Individuals engage in self-injurious behaviours to reduce negative mental and cognitive states or evoke positive emotions.
