Objective To evaluate the clinical efficacy of the combined treatment with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) on hepatocellular carcinoma (HCC) .Methods 312 patien...Objective To evaluate the clinical efficacy of the combined treatment with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) on hepatocellular carcinoma (HCC) .Methods 312 patients with moderate or advanced HCCs were divided into two groups; 170 cases underwent TACE treatment alone, 142 cases were treated with TACE and PEI under B-ultrasound guidance.Results The rates of reduction in tumor diameter and the decline in serum AFP level were 41.2% and 40.4% in the TACE group and 75.4% and 74.1 % in the TACE + PEI group respectively. The 6, 12 and 24 months survival rates in the TACE group were 77.1 % , 34.1% and 18.8% ,respectively and in the TACE + PEI group 87.3% , 62.0% and 38.0% , respectively. Overall, there was a significant difference between the two treatment groups ( P < 0.05). Conclusion Treatment on HCCs with TACE + PEI is convenient, safe and results in better survival rates than TACE alone.展开更多
Objective:To analyze the imaging results of hepatic epithelioid hemangioendothelioma(HEHE)and the effect of transhepatic arterial embolization(TAE)combined with microwave ablation(MWA)in the treatment of HEHE.Methods:...Objective:To analyze the imaging results of hepatic epithelioid hemangioendothelioma(HEHE)and the effect of transhepatic arterial embolization(TAE)combined with microwave ablation(MWA)in the treatment of HEHE.Methods:A retrospective analysis of four patients with HEHE diagnosed by pathological diagnosis of liver biopsy was performed.展开更多
Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological me...Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.展开更多
Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It ...Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
Human cardiac organoids have revolutionized the study of cardiac development,disease modeling,drug discovery,and regenerative therapies.This review systematically discusses strategies and progress in the construction ...Human cardiac organoids have revolutionized the study of cardiac development,disease modeling,drug discovery,and regenerative therapies.This review systematically discusses strategies and progress in the construction of cardiac organoids,categorizing them into three main types:cardiac spheroids,self-organizing/assembloid organoids,and organoid-on-a-chip systems.This review uniquely integrates the advances in vascularization,organ-on-chip design,and environmental cardiotoxicity modeling within cardiac organoid platforms,offering a critical synthesis that is absent in the literature.In the context of escalating environmental threats to cardiovascular health,there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action.This review highlights advances in cardiac organoid applications for disease modeling—including congenital heart defects and acquired cardiovascular diseases—drug development,toxicity screening,and the study of environmentally induced cardiovascular pathogenesis.In addition,it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches.Finally,we propose future directions for developing standardized cardiac organoid platforms with clinical predictability,aiming to expand the utility of this technology across broader research applications.展开更多
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
The retrospective study by Edwar et al reinforces the role of therapeutic penetrating keratoplasty(PK)as a vital intervention in severe,treatment-resistant infectious keratitis.In advanced cases—often complicated by ...The retrospective study by Edwar et al reinforces the role of therapeutic penetrating keratoplasty(PK)as a vital intervention in severe,treatment-resistant infectious keratitis.In advanced cases—often complicated by trauma,delayed presentation,and corneal perforation—PK restores globe integrity and provides limited visual recovery.However,its application is constrained by graft-related complications and donor shortages,particularly in low-resource settings.These limitations highlight the need for earlier,globe-sparing strategies to prevent progression and reduce surgical demand.Photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL)has emerged as a promising adjunct or alternative.With both antimicrobial and tissue-stabilizing effects,PACK-CXL may control infection and preserve corneal structure in earlier stages.A layered treatment framework that incorporates PACK-CXL as an initial intervention and reserves PK for refractory cases may help improve clinical outcomes.Further studies are needed to define their best use in practice.展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Middle meningeal artery embolization(MMAE)has revolutionized chronic subdural hematoma management,yet procedural risks persist due to anatomical variability.We analyze a case report by Zhao et al describing transient ...Middle meningeal artery embolization(MMAE)has revolutionized chronic subdural hematoma management,yet procedural risks persist due to anatomical variability.We analyze a case report by Zhao et al describing transient diplopia caused by inadvertent embolization of the lacrimal artery via a dynamic middle meningeal–ophthalmic anastomosis.This correspondence advances three critical innovations in MMAE safety.First,intraoperative anastomotic unmasking—exposing occult middle meningeal-ophthalmic collaterals during particle injection—reveals dynamic vascular behavior missed by preoperative angiography,underscoring the need for adaptive imaging protocols.Second,hybrid embolization(liquid agents for proximal occlusion+particles for distal control)balances precision and safety,reducing reflux risks compared to monotherapy.Third,a 108-day follow-up establishes a benchmark for functional recovery,challenging assumptions about irreversible cranial nerve injuries and emphasizing structured postprocedural care.Collectively,these findings advocate for procedural agility,multimodal embolic strategies,and sustained rehabilitation to optimize MMAE outcomes while minimizing iatrogenic harm.展开更多
Endoscopic ultrasound(EUS)guided vascular interventions have expanded the reach of therapeutic endoscopy to include vascular pathology previously inaccessible by endoscopists.Gastric variceal bleeding comprises 20%of ...Endoscopic ultrasound(EUS)guided vascular interventions have expanded the reach of therapeutic endoscopy to include vascular pathology previously inaccessible by endoscopists.Gastric variceal bleeding comprises 20%of all variceal bleeding and is associated with high morbidity and mortality.Historically,endoscopic injection of thrombosis-inducing agents such as glue has been used.However,glue injection carries potential risks including systemic embolization,damage to the endoscope,and recurrent bleeding.The introduction of hemostatic coils has revolutionized the endoscopic approach,with EUS-guided coil embolization emerging as an effective and safe modality for the management of gastric varices(GVs).When compared with conventional glue injection,EUSguided embolization is associated with improved visualization,higher efficacy,and better safety profile.Despite its expanding adoption,the standardization of EUS guided embolization remains a challenge.High-quality studies are needed to standardize this promising technique and define its role in clinical practice.In this review,we will discuss the indications,efficacy,techniques,and various approaches for EUS-guided embolization of GVs.展开更多
The Kakinuma et al’s case report shows that non-pregnancy-related arterial pseudoaneurysm is a relatively rare,little known by some gynecologists,endo-scopists,surgeons or radiologists,which can cause massive bleedin...The Kakinuma et al’s case report shows that non-pregnancy-related arterial pseudoaneurysm is a relatively rare,little known by some gynecologists,endo-scopists,surgeons or radiologists,which can cause massive bleeding.Arterial pseudoaneurysm is a condition in which the wall of a blood vessel collapses due to some invasive event,and the resulting leaked blood is engulfed by soft tissues,forming a cavity that is in communication with the vessel.It is a potentially life-threatening complication that could occurs after some deliveries and some gynecological invasive procedures.Remarkably,an undetermined percentage of pseudoaneurysms are asymptomatic,and in an asymptomatic patient it is difficult to predict the risk of haemorrhage and the attitude to follow,which depends on several factors,such as,the size and location of the vessel involved,changes in the size of the pseudoaneurysm,or the available therapeutic resources to be offered to patients,among others circumstances.The management of abdominal arterial pseudoaneurysm does not have consistent scientific evidence,but it seems that,regardless of the associated circumstances,the pseudoaneurysm could be treated at least initially,and mainly,through endovascular procedures,as done by Kakinuma et al.展开更多
In this review research,the full bio-medical potential and application of the severe acute respiratory syndrome(SARS)-CoV-2 viruses are discussed in detail with the aim of discovering innovative treatment strategies i...In this review research,the full bio-medical potential and application of the severe acute respiratory syndrome(SARS)-CoV-2 viruses are discussed in detail with the aim of discovering innovative treatment strategies in virology and medicine.The SARS-CoV-2 which caused an international health crisis also unraveled an opportunity to gain from its pathogenic effects to treat the affected people.The study aims at testing whether the newly discovered SARS-CoV-2 can be used for therapeutic and clinical purposes.With in-depth analytics,this investigation issue endeavors to unearth new ways of fighting infectious diseases and to improve existing medical interventions.Beside scientific and practical significance the role of this work is vital.By learning the biologic and molecular mysteries of SARS-CoV-2,the researchers can create precise medicines and vaccines not only against COVID-19 but also the other infectious diseases as well.Furthermore,this recommendation may open the door to the future development of gene therapy and vaccine technology.In this sense,it combines multiple approaches,such as viral studies,immunology,and molecular biology.Laboratory experiments,computer program modeling and clinical trials are applied to detection of the SARS-COV-2 in therapeutic implementation.The principal conclusion and analysis of this research put forth the fact that SARS-CoV-2 can be utilized in anti-viral treatment,cancer therapy,and vaccine programs.The study results confirm the inherent adaptability of viruses like SARS-CoV-2 and emphasis on the development of specific therapeutic measures.It is valuable because of its potential to add to virology and medication,showing new ways for virus-based treatment.In addition,the impact of these results on treatments would be revolutionary,with potential to invent superior and flexible interventions against infectious disease.In short,the therapeutic use of SARS-CoV-2 can be regarded as a bold innovation with tremendous consequences for general health,and ultimately for medical science.展开更多
Biology is governed by macromolecular interactions,perturbation of which often lies at the heart of disease.Most therapeutic drugs,whether they are small molecules or biologics,exert their effects through impeding suc...Biology is governed by macromolecular interactions,perturbation of which often lies at the heart of disease.Most therapeutic drugs,whether they are small molecules or biologics,exert their effects through impeding such interactions,whether they are of an enzyme with its substrate or a ligand with its receptor.Conversely,a handful of approved drugs and a larger number of candidates in development have the opposite effect:They either activate or inhibit a biological output by stabilizing a preexisting complex through reducing the rate at which its components dissociate(koff).展开更多
Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the S...Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution ofLigands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA,proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents,including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications thatenhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complexphysiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencingmolecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. Byengineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts,these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacywhile minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors,have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treatinga range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecularmechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative andeffective therapeutic interventions.展开更多
AIM To explore the therapeutic effect of chemoembolization in hepatic metastases in colorectal carcinoma. METHODS Forty patients underwent chemoembolization of metastatic liver lesion from colorectal carcinoma. Sel...AIM To explore the therapeutic effect of chemoembolization in hepatic metastases in colorectal carcinoma. METHODS Forty patients underwent chemoembolization of metastatic liver lesion from colorectal carcinoma. Selective angiography of the hepatic artery was performed to identify the feeding vessels of the metastatic lesion. The injected chemoemulsum consisted of 100*!mg 5 fluorouracil, 10*!mg mitomycin C and 10*!mL lipiodol ultra fluid in a total volume of 30*!mL . Gel foam embolization then followed until stagnation of blood flow was achieved. Patients were evaluated for response, over all survival, and side effects. RESULTS Overall median survival time from date of first chemoembolization was ten months. Median survival time of cirrhotic patients with class A and B by Child Pugh classification was 24 and 3 months, respectively. The difference was significant, ( P <0 01) . Patients with metastatic disease confined to the liver did better than those who also had extrahepatic disease, with median survivals of 14 and 3 months, respectively ( P <0 02) . There were significant differences in that median survival of patients with hypervascular metastases was longer than that of patients with hypovascular metastases. The most common side effects were transient fever, abdominal pain and fatigue. Three patients died within one month from the procedure. CONCLUSION The therapeutic effect of systemic chemotherapy in hepatic metastases of large intestinal carcinoma was not satisfactory and there were more side effects, whereas the therapeutic effect of selective chemoembolization was promising and there were less side effects. Selective chemoembolization may be an effective first line therapy in hepatic metastases of large intestinal carcinoma.展开更多
It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing a...It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.展开更多
Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and...Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart disease.In that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
文摘Objective To evaluate the clinical efficacy of the combined treatment with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) on hepatocellular carcinoma (HCC) .Methods 312 patients with moderate or advanced HCCs were divided into two groups; 170 cases underwent TACE treatment alone, 142 cases were treated with TACE and PEI under B-ultrasound guidance.Results The rates of reduction in tumor diameter and the decline in serum AFP level were 41.2% and 40.4% in the TACE group and 75.4% and 74.1 % in the TACE + PEI group respectively. The 6, 12 and 24 months survival rates in the TACE group were 77.1 % , 34.1% and 18.8% ,respectively and in the TACE + PEI group 87.3% , 62.0% and 38.0% , respectively. Overall, there was a significant difference between the two treatment groups ( P < 0.05). Conclusion Treatment on HCCs with TACE + PEI is convenient, safe and results in better survival rates than TACE alone.
文摘Objective:To analyze the imaging results of hepatic epithelioid hemangioendothelioma(HEHE)and the effect of transhepatic arterial embolization(TAE)combined with microwave ablation(MWA)in the treatment of HEHE.Methods:A retrospective analysis of four patients with HEHE diagnosed by pathological diagnosis of liver biopsy was performed.
基金supported by the National Natural Science Foundation of China,No.82274304(to YH)the Major Clinical Study Projects of Shanghai Shenkang Hospital Development Center,No.SHDC2020CR2046B(to YH)Shanghai Municipal Health Commission Talent Plan,No.2022LJ010(to YH).
文摘Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels,often leading to stroke and dementia.Due to its diverse etiologies and complex pathological mechanisms,preventing and treating cerebral small vessel vasculopathy is challenging.Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis.Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease.This review begins with a comprehensive introduction to the structure,function,and driving factors of the glymphatic system,highlighting its essential role in brain waste clearance.Afterwards,cerebral small vessel disease was reviewed from the perspective of the glymphatic system,after which the mechanisms underlying their correlation were summarized.Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain,thereby exacerbating the pathological processes associated with cerebral small vessel disease.The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease:arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease.Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system.However,the effectiveness of its parameters needs to be enhanced.Among various nervous system diseases,including cerebral small vessel disease,glymphatic failure may be a common final pathway toward dementia.Overall,this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.
基金supported by Italian Ministry of Health Ricerca Corrente [RC 2023] and RF-2016-02361294supported by#NEXTGENERATIONEU (NGEU)+3 种基金funded by the Ministry of University and Research (MUR)National Recovery and Resilience Plan (NRRP)project MNESYS (PE0000006)–A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022)(to FRG)partially supported by a grant from Fondazione Romeo ed Enrica Invernizzi (to FRG)。
文摘Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金supported by the Innovation Promotion Program of NHC and Shanghai Key Labs,SIBPT(grant number PT2025-01)。
文摘Human cardiac organoids have revolutionized the study of cardiac development,disease modeling,drug discovery,and regenerative therapies.This review systematically discusses strategies and progress in the construction of cardiac organoids,categorizing them into three main types:cardiac spheroids,self-organizing/assembloid organoids,and organoid-on-a-chip systems.This review uniquely integrates the advances in vascularization,organ-on-chip design,and environmental cardiotoxicity modeling within cardiac organoid platforms,offering a critical synthesis that is absent in the literature.In the context of escalating environmental threats to cardiovascular health,there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action.This review highlights advances in cardiac organoid applications for disease modeling—including congenital heart defects and acquired cardiovascular diseases—drug development,toxicity screening,and the study of environmentally induced cardiovascular pathogenesis.In addition,it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches.Finally,we propose future directions for developing standardized cardiac organoid platforms with clinical predictability,aiming to expand the utility of this technology across broader research applications.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
文摘The retrospective study by Edwar et al reinforces the role of therapeutic penetrating keratoplasty(PK)as a vital intervention in severe,treatment-resistant infectious keratitis.In advanced cases—often complicated by trauma,delayed presentation,and corneal perforation—PK restores globe integrity and provides limited visual recovery.However,its application is constrained by graft-related complications and donor shortages,particularly in low-resource settings.These limitations highlight the need for earlier,globe-sparing strategies to prevent progression and reduce surgical demand.Photoactivated chromophore for infectious keratitis-corneal collagen cross-linking(PACK-CXL)has emerged as a promising adjunct or alternative.With both antimicrobial and tissue-stabilizing effects,PACK-CXL may control infection and preserve corneal structure in earlier stages.A layered treatment framework that incorporates PACK-CXL as an initial intervention and reserves PK for refractory cases may help improve clinical outcomes.Further studies are needed to define their best use in practice.
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
文摘Middle meningeal artery embolization(MMAE)has revolutionized chronic subdural hematoma management,yet procedural risks persist due to anatomical variability.We analyze a case report by Zhao et al describing transient diplopia caused by inadvertent embolization of the lacrimal artery via a dynamic middle meningeal–ophthalmic anastomosis.This correspondence advances three critical innovations in MMAE safety.First,intraoperative anastomotic unmasking—exposing occult middle meningeal-ophthalmic collaterals during particle injection—reveals dynamic vascular behavior missed by preoperative angiography,underscoring the need for adaptive imaging protocols.Second,hybrid embolization(liquid agents for proximal occlusion+particles for distal control)balances precision and safety,reducing reflux risks compared to monotherapy.Third,a 108-day follow-up establishes a benchmark for functional recovery,challenging assumptions about irreversible cranial nerve injuries and emphasizing structured postprocedural care.Collectively,these findings advocate for procedural agility,multimodal embolic strategies,and sustained rehabilitation to optimize MMAE outcomes while minimizing iatrogenic harm.
文摘Endoscopic ultrasound(EUS)guided vascular interventions have expanded the reach of therapeutic endoscopy to include vascular pathology previously inaccessible by endoscopists.Gastric variceal bleeding comprises 20%of all variceal bleeding and is associated with high morbidity and mortality.Historically,endoscopic injection of thrombosis-inducing agents such as glue has been used.However,glue injection carries potential risks including systemic embolization,damage to the endoscope,and recurrent bleeding.The introduction of hemostatic coils has revolutionized the endoscopic approach,with EUS-guided coil embolization emerging as an effective and safe modality for the management of gastric varices(GVs).When compared with conventional glue injection,EUSguided embolization is associated with improved visualization,higher efficacy,and better safety profile.Despite its expanding adoption,the standardization of EUS guided embolization remains a challenge.High-quality studies are needed to standardize this promising technique and define its role in clinical practice.In this review,we will discuss the indications,efficacy,techniques,and various approaches for EUS-guided embolization of GVs.
文摘The Kakinuma et al’s case report shows that non-pregnancy-related arterial pseudoaneurysm is a relatively rare,little known by some gynecologists,endo-scopists,surgeons or radiologists,which can cause massive bleeding.Arterial pseudoaneurysm is a condition in which the wall of a blood vessel collapses due to some invasive event,and the resulting leaked blood is engulfed by soft tissues,forming a cavity that is in communication with the vessel.It is a potentially life-threatening complication that could occurs after some deliveries and some gynecological invasive procedures.Remarkably,an undetermined percentage of pseudoaneurysms are asymptomatic,and in an asymptomatic patient it is difficult to predict the risk of haemorrhage and the attitude to follow,which depends on several factors,such as,the size and location of the vessel involved,changes in the size of the pseudoaneurysm,or the available therapeutic resources to be offered to patients,among others circumstances.The management of abdominal arterial pseudoaneurysm does not have consistent scientific evidence,but it seems that,regardless of the associated circumstances,the pseudoaneurysm could be treated at least initially,and mainly,through endovascular procedures,as done by Kakinuma et al.
文摘In this review research,the full bio-medical potential and application of the severe acute respiratory syndrome(SARS)-CoV-2 viruses are discussed in detail with the aim of discovering innovative treatment strategies in virology and medicine.The SARS-CoV-2 which caused an international health crisis also unraveled an opportunity to gain from its pathogenic effects to treat the affected people.The study aims at testing whether the newly discovered SARS-CoV-2 can be used for therapeutic and clinical purposes.With in-depth analytics,this investigation issue endeavors to unearth new ways of fighting infectious diseases and to improve existing medical interventions.Beside scientific and practical significance the role of this work is vital.By learning the biologic and molecular mysteries of SARS-CoV-2,the researchers can create precise medicines and vaccines not only against COVID-19 but also the other infectious diseases as well.Furthermore,this recommendation may open the door to the future development of gene therapy and vaccine technology.In this sense,it combines multiple approaches,such as viral studies,immunology,and molecular biology.Laboratory experiments,computer program modeling and clinical trials are applied to detection of the SARS-COV-2 in therapeutic implementation.The principal conclusion and analysis of this research put forth the fact that SARS-CoV-2 can be utilized in anti-viral treatment,cancer therapy,and vaccine programs.The study results confirm the inherent adaptability of viruses like SARS-CoV-2 and emphasis on the development of specific therapeutic measures.It is valuable because of its potential to add to virology and medication,showing new ways for virus-based treatment.In addition,the impact of these results on treatments would be revolutionary,with potential to invent superior and flexible interventions against infectious disease.In short,the therapeutic use of SARS-CoV-2 can be regarded as a bold innovation with tremendous consequences for general health,and ultimately for medical science.
文摘Biology is governed by macromolecular interactions,perturbation of which often lies at the heart of disease.Most therapeutic drugs,whether they are small molecules or biologics,exert their effects through impeding such interactions,whether they are of an enzyme with its substrate or a ligand with its receptor.Conversely,a handful of approved drugs and a larger number of candidates in development have the opposite effect:They either activate or inhibit a biological output by stabilizing a preexisting complex through reducing the rate at which its components dissociate(koff).
基金Key research and development projects of Sichuan Science and Technology Plan Project(2024YFFK0135)Fujian Provincial Natural Science Foundation of China(2024J011450).
文摘Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging aspivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution ofLigands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA,proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents,including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications thatenhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complexphysiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencingmolecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. Byengineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts,these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacywhile minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors,have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treatinga range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecularmechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative andeffective therapeutic interventions.
文摘AIM To explore the therapeutic effect of chemoembolization in hepatic metastases in colorectal carcinoma. METHODS Forty patients underwent chemoembolization of metastatic liver lesion from colorectal carcinoma. Selective angiography of the hepatic artery was performed to identify the feeding vessels of the metastatic lesion. The injected chemoemulsum consisted of 100*!mg 5 fluorouracil, 10*!mg mitomycin C and 10*!mL lipiodol ultra fluid in a total volume of 30*!mL . Gel foam embolization then followed until stagnation of blood flow was achieved. Patients were evaluated for response, over all survival, and side effects. RESULTS Overall median survival time from date of first chemoembolization was ten months. Median survival time of cirrhotic patients with class A and B by Child Pugh classification was 24 and 3 months, respectively. The difference was significant, ( P <0 01) . Patients with metastatic disease confined to the liver did better than those who also had extrahepatic disease, with median survivals of 14 and 3 months, respectively ( P <0 02) . There were significant differences in that median survival of patients with hypervascular metastases was longer than that of patients with hypovascular metastases. The most common side effects were transient fever, abdominal pain and fatigue. Three patients died within one month from the procedure. CONCLUSION The therapeutic effect of systemic chemotherapy in hepatic metastases of large intestinal carcinoma was not satisfactory and there were more side effects, whereas the therapeutic effect of selective chemoembolization was promising and there were less side effects. Selective chemoembolization may be an effective first line therapy in hepatic metastases of large intestinal carcinoma.
基金supported by the National Natural Science Foundation of China,Nos.82274313(to YD),82204746(to ML),82003982(to TL).
文摘It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.
基金supported by JSPS KAKENHI Grant Number JP24K18622(to TI)JSPS KAKENHI Grant Number JP23K18451(to TM)。
文摘Stroke causes neuronal loss,which ultimately results in persistent neurological dysfunction.Globally,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart disease.In that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
