Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and th...Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.展开更多
BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma.Consequently,a definitive diagnosis primarily relies on his-tological results.The ultrasound(US)-guide...BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma.Consequently,a definitive diagnosis primarily relies on his-tological results.The ultrasound(US)-guided coaxial core needle biopsy(CNB)not only procures sufficient tissue to help clarify the diagnosis,but reduces the incidence of puncture-related complications.CASE SUMMARY A 41-year-old female,with a history of pulmonary tuberculosis,was admitted to our hospital with multiple indeterminate splenic lesions.Gray-scale ultrasono-graphy demonstrated splenomegaly with numerous well-defined hypoechoic ma-sses.Abdominal contrast-enhanced computed tomography(CT)showed an en-larged spleen with multiple irregular-shaped,peripherally enhancing,hypodense lesions.Positron emission CT revealed numerous abnormal hyperglycemia foci.These imaging findings strongly indicated the possibility of infectious disease as the primary concern,with neoplastic lesions requiring exclusion.To obtain the precise pathological diagnosis,the US-guided coaxial CNB of the spleen was ca-rried out.The patient did not express any discomfort during the procedure.CONCLUSION Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples,as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and sur-rounding tissue.展开更多
Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape ...Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.展开更多
A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in...A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.展开更多
CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expresse...CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.展开更多
BACKGROUND Splenic rupture associated with Behçet’s syndrome(BS)is extremely rare,and there is no consensus on its management.In this case report,a patient with BSassociated splenic rupture was successfully trea...BACKGROUND Splenic rupture associated with Behçet’s syndrome(BS)is extremely rare,and there is no consensus on its management.In this case report,a patient with BSassociated splenic rupture was successfully treated with splenic artery embolization(SAE)and had a good prognosis after the intervention.CASE SUMMARY The patient was admitted for pain in the left upper abdominal quadrant.He was diagnosed with splenic rupture.Multiple oral and genital aphthous ulcers were observed,and acne scars were found on his back.He had a 2-year history of BS diagnosis,with symptoms of oral and genital ulcers.At that time,he was treated with oral corticosteroids for 1 month,but the symptoms did not alleviate.He underwent SAE to treat the rupture.On the first day after SAE,the patient reported a complete resolution of abdominal pain and was discharged 5 d later.Three months after the intervention,a computed tomography examination showed that the splenic hematoma had formed a stable cystic effusion,suggesting a good prognosis.CONCLUSION SAE might be a good choice for BS-associated splenic rupture based on good surgical practice and material selection.展开更多
Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medi...Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medical literature. Unfortunately, when conflicting guidelines for a specific disease are published, confusion results. Purpose: This article provides a suggested guideline outcome measure that would benefit the physician and patient. Methods: A review of 19 different guidelines for cardiovascular disease treatment is one example of the lack of specific outcomes that currently exist. The basic problem with most guidelines is that they do not state the expected end result (i.e., the benefit to the patient) if that guideline is followed. When guidelines use cardiovascular disease risk factors to dictate therapy, the end benefit is never stated so that the patient can make an appropriate choice of which (if any) guideline to follow. Results: A good example is guidelines published by the American Heart Association for reducing cardiovascular disease. These guidelines are risk factor based and only indicate that cardiovascular disease would be reduced if followed. No specific percentage in the reduction of the incidence of disease is given. In contrast, when elimination of the disease is the stated goal of the guideline, the end result is clear. To date, this goal has been stated by only one organization devoted to eliminating cardiovascular disease. Conclusion: Guidelines need to be written to provide the physician and the patient with a specific end point that is expected when the guideline is followed. Patient acceptance and compliance will be much improved if the patient knows the risk/benefit of following the guideline’s recommendations.展开更多
Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NAD...Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.展开更多
AIM:To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages,limitations,and possible solutions common to all tasks.METHODS:We searche...AIM:To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages,limitations,and possible solutions common to all tasks.METHODS:We searched three academic databases,including PubMed,Web of Science,and Ovid,with the date of August 2022.We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords,of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images.RESULTS:Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance,including diabetic retinopathy,glaucoma,age-related macular degeneration,retinal vein occlusions,retinal detachment,and other peripheral retinal diseases.Compared to fundus images,the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200°in a single exposure,which can observe more areas of the retina.CONCLUSION:The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.展开更多
ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosi...ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.展开更多
Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esth...Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.展开更多
Loss of neurons and disruption of neural circuits are associated with many neurological diseases,including neurodegenerative diseases and mental disorders.The most prevalent pathological feature of neurodegenerative d...Loss of neurons and disruption of neural circuits are associated with many neurological diseases,including neurodegenerative diseases and mental disorders.The most prevalent pathological feature of neurodegenerative diseases is the aggregate loss of certain neuronal populations.For example,the loss of dopamine(DA)neurons in the substantia nigra pars compacta has been defined as a pathological hallmark of Parkinson’s disease(PD;Kamath et al.,2022).展开更多
The differential diagnosis of neurodegenerative diseases is complex and relies on clinical assessment,biomarker levels in cerebrospinal fluid,neuroimaging and neuropsychological assessment.The efforts of the scientifi...The differential diagnosis of neurodegenerative diseases is complex and relies on clinical assessment,biomarker levels in cerebrospinal fluid,neuroimaging and neuropsychological assessment.The efforts of the scientific community are focused on two aspects:a)the discovery of minimally invasive biomarkers;b)the discovery of early biomarkers that can predict the progression to clinical disease in the presymptomatic stage of a disease.Considering the impact of the number of patients affected by chronic neurodegenerative diseases on public health expenditures,early diagnosis seems to be a primary need of our society.展开更多
Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseas...Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.展开更多
Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from dam...Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.展开更多
Brain-derived neurotrophic factor(BDNF)is one of the neurotrophins,a specific polypeptide growth factor,which plays a crucial role in the proliferation,differentiation,survival,and death of neurons and non-neuronal ce...Brain-derived neurotrophic factor(BDNF)is one of the neurotrophins,a specific polypeptide growth factor,which plays a crucial role in the proliferation,differentiation,survival,and death of neurons and non-neuronal cells.It is not only essential to maintain the balance between death on one side and survival of neurons on the other,but also it mediates additional higher-order activities such as learning,memory,and behavior.It is initially synthesized as a precursor protein,proBDNF,that can be secreted as it is or it can be cleaved intracellularly by furin and proconvertases,or extracellularly by extracellular proteases such as matrix metalloprotease-9 and matrix metalloprotease-2,or plasmin to give mature BDNF.展开更多
Pneumoconiosis is a group of heterogeneous fibrotic lung diseases caused by inorganic mineral dust and includes coal workers’pneumoconiosis and silicosis.Silicosis involves diffuse or nodular interstitial pulmonary f...Pneumoconiosis is a group of heterogeneous fibrotic lung diseases caused by inorganic mineral dust and includes coal workers’pneumoconiosis and silicosis.Silicosis involves diffuse or nodular interstitial pulmonary fibrosis caused by exposure to asbestos or silica dust.China is thought to have the highest number of silicosis cases,with 6,000 new cases reported annually^([1]).Currently,the clinical diagnosis and monitoring of silicosis relies mainly on a history of occupational exposure and radiological abnormalities^([2]).Therefore,determining further indicators is crucial to reflect the severity of silicosis.展开更多
BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to ex...BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.展开更多
BACKGROUND Partial splenic embolization(PSE)has been suggested as an alternative to splenectomy in the treatment of hypersplenism.However,some patients may experience recurrence of hypersplenism after PSE and require ...BACKGROUND Partial splenic embolization(PSE)has been suggested as an alternative to splenectomy in the treatment of hypersplenism.However,some patients may experience recurrence of hypersplenism after PSE and require splenectomy.Currently,there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications.AIM To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism.METHODS Between January 2010 and December 2021,321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department.Based on whether PSE was performed prior to splenectomy,the patients were divided into two groups:PSE group(n=40)and non-PSE group(n=281).Patient characteristics,postoperative complications,and follow-up data were compared between groups.Propensity score matching(PSM)was conducted,and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding(IB).The receiver operating characteristic curve,Hosmer-Lemeshow goodness-of-fit test,and decision curve analysis(DCA)were employed to evaluate the differentiation,calibration,and clinical performance of the model.RESULTS After PSM,the non-PSE group showed significant reductions in hospital stay,intraoperative blood loss,and operation time(all P=0.00).Multivariate analysis revealed that spleen length,portal vein diameter,splenic vein diameter,and history of PSE were independent predictive factors for IB.A nomogram predictive model of IB was constructed,and DCA demonstrated the clinical utility of this model.Both groups exhibited similar results in terms of overall survival during the follow-up period.CONCLUSION Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.展开更多
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金supported by Association 2HE(Center for Human Health and Environment)by Regione Puglia-Grant Malattie Rare DUP n.246 of 2019(to CB).
文摘Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.
文摘BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma.Consequently,a definitive diagnosis primarily relies on his-tological results.The ultrasound(US)-guided coaxial core needle biopsy(CNB)not only procures sufficient tissue to help clarify the diagnosis,but reduces the incidence of puncture-related complications.CASE SUMMARY A 41-year-old female,with a history of pulmonary tuberculosis,was admitted to our hospital with multiple indeterminate splenic lesions.Gray-scale ultrasono-graphy demonstrated splenomegaly with numerous well-defined hypoechoic ma-sses.Abdominal contrast-enhanced computed tomography(CT)showed an en-larged spleen with multiple irregular-shaped,peripherally enhancing,hypodense lesions.Positron emission CT revealed numerous abnormal hyperglycemia foci.These imaging findings strongly indicated the possibility of infectious disease as the primary concern,with neoplastic lesions requiring exclusion.To obtain the precise pathological diagnosis,the US-guided coaxial CNB of the spleen was ca-rried out.The patient did not express any discomfort during the procedure.CONCLUSION Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples,as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and sur-rounding tissue.
文摘Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.
基金financially supported by the National Natural Science Foundation of China,No.32002235(to MT)the Science and Technology Foundation of Taian of Shandong Province,No.2020NS216(to XL)。
文摘A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.
基金supported by the National Major Project of Research and Development,No.2022YFA1105500(to SZ)the National Natural Science Foundation of China,No.81870975(to SZ)Innovation Program for Graduate Students in Jiangsu Province of China,No.KYCX223335(to MZ)。
文摘CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.
文摘BACKGROUND Splenic rupture associated with Behçet’s syndrome(BS)is extremely rare,and there is no consensus on its management.In this case report,a patient with BSassociated splenic rupture was successfully treated with splenic artery embolization(SAE)and had a good prognosis after the intervention.CASE SUMMARY The patient was admitted for pain in the left upper abdominal quadrant.He was diagnosed with splenic rupture.Multiple oral and genital aphthous ulcers were observed,and acne scars were found on his back.He had a 2-year history of BS diagnosis,with symptoms of oral and genital ulcers.At that time,he was treated with oral corticosteroids for 1 month,but the symptoms did not alleviate.He underwent SAE to treat the rupture.On the first day after SAE,the patient reported a complete resolution of abdominal pain and was discharged 5 d later.Three months after the intervention,a computed tomography examination showed that the splenic hematoma had formed a stable cystic effusion,suggesting a good prognosis.CONCLUSION SAE might be a good choice for BS-associated splenic rupture based on good surgical practice and material selection.
文摘Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medical literature. Unfortunately, when conflicting guidelines for a specific disease are published, confusion results. Purpose: This article provides a suggested guideline outcome measure that would benefit the physician and patient. Methods: A review of 19 different guidelines for cardiovascular disease treatment is one example of the lack of specific outcomes that currently exist. The basic problem with most guidelines is that they do not state the expected end result (i.e., the benefit to the patient) if that guideline is followed. When guidelines use cardiovascular disease risk factors to dictate therapy, the end benefit is never stated so that the patient can make an appropriate choice of which (if any) guideline to follow. Results: A good example is guidelines published by the American Heart Association for reducing cardiovascular disease. These guidelines are risk factor based and only indicate that cardiovascular disease would be reduced if followed. No specific percentage in the reduction of the incidence of disease is given. In contrast, when elimination of the disease is the stated goal of the guideline, the end result is clear. To date, this goal has been stated by only one organization devoted to eliminating cardiovascular disease. Conclusion: Guidelines need to be written to provide the physician and the patient with a specific end point that is expected when the guideline is followed. Patient acceptance and compliance will be much improved if the patient knows the risk/benefit of following the guideline’s recommendations.
基金supported by the National Research Foundation of the Republic of Korea 2018R1D1A3B07047960the Soonchunhyang University Research Fund(to SSY).
文摘Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.
基金Supported by 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21025).
文摘AIM:To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages,limitations,and possible solutions common to all tasks.METHODS:We searched three academic databases,including PubMed,Web of Science,and Ovid,with the date of August 2022.We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords,of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images.RESULTS:Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance,including diabetic retinopathy,glaucoma,age-related macular degeneration,retinal vein occlusions,retinal detachment,and other peripheral retinal diseases.Compared to fundus images,the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200°in a single exposure,which can observe more areas of the retina.CONCLUSION:The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.
文摘ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China Grants(82370945, 82171001, 82222015 and 82370915)Research Funding from West China School/Hospital of Stomatology Sichuan University(RCDWJS2023-1)。
文摘Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.
基金supported by the National Natural Science Foundation of China,No.81971133Liaoning Key Research and Development Project,No.2021JH2/10300059Liaoning Revitalization Talents Prograrn,No.XLYC2002109(all to GL)。
文摘Loss of neurons and disruption of neural circuits are associated with many neurological diseases,including neurodegenerative diseases and mental disorders.The most prevalent pathological feature of neurodegenerative diseases is the aggregate loss of certain neuronal populations.For example,the loss of dopamine(DA)neurons in the substantia nigra pars compacta has been defined as a pathological hallmark of Parkinson’s disease(PD;Kamath et al.,2022).
基金supported by grants from the Italian Ministry of Health(Ricerca Corrente to FRB,DG,GMT)。
文摘The differential diagnosis of neurodegenerative diseases is complex and relies on clinical assessment,biomarker levels in cerebrospinal fluid,neuroimaging and neuropsychological assessment.The efforts of the scientific community are focused on two aspects:a)the discovery of minimally invasive biomarkers;b)the discovery of early biomarkers that can predict the progression to clinical disease in the presymptomatic stage of a disease.Considering the impact of the number of patients affected by chronic neurodegenerative diseases on public health expenditures,early diagnosis seems to be a primary need of our society.
基金RN received funding from Swiss Centre for Applied Human ToxicologyHelmut Hortun Stiftung。
文摘Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.
文摘Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
基金funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 765704(to CR).
文摘Brain-derived neurotrophic factor(BDNF)is one of the neurotrophins,a specific polypeptide growth factor,which plays a crucial role in the proliferation,differentiation,survival,and death of neurons and non-neuronal cells.It is not only essential to maintain the balance between death on one side and survival of neurons on the other,but also it mediates additional higher-order activities such as learning,memory,and behavior.It is initially synthesized as a precursor protein,proBDNF,that can be secreted as it is or it can be cleaved intracellularly by furin and proconvertases,or extracellularly by extracellular proteases such as matrix metalloprotease-9 and matrix metalloprotease-2,or plasmin to give mature BDNF.
基金supported by the scientific research project of Hunan Prevention and Treatment Institute for Occupational Diseases in 2021(Y2021-013)。
文摘Pneumoconiosis is a group of heterogeneous fibrotic lung diseases caused by inorganic mineral dust and includes coal workers’pneumoconiosis and silicosis.Silicosis involves diffuse or nodular interstitial pulmonary fibrosis caused by exposure to asbestos or silica dust.China is thought to have the highest number of silicosis cases,with 6,000 new cases reported annually^([1]).Currently,the clinical diagnosis and monitoring of silicosis relies mainly on a history of occupational exposure and radiological abnormalities^([2]).Therefore,determining further indicators is crucial to reflect the severity of silicosis.
文摘BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.
基金Supported by National Natural Science Foundations of China,No.82174160and Anhui Natural Science Foundation,No.2008085QH389。
文摘BACKGROUND Partial splenic embolization(PSE)has been suggested as an alternative to splenectomy in the treatment of hypersplenism.However,some patients may experience recurrence of hypersplenism after PSE and require splenectomy.Currently,there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications.AIM To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism.METHODS Between January 2010 and December 2021,321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department.Based on whether PSE was performed prior to splenectomy,the patients were divided into two groups:PSE group(n=40)and non-PSE group(n=281).Patient characteristics,postoperative complications,and follow-up data were compared between groups.Propensity score matching(PSM)was conducted,and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding(IB).The receiver operating characteristic curve,Hosmer-Lemeshow goodness-of-fit test,and decision curve analysis(DCA)were employed to evaluate the differentiation,calibration,and clinical performance of the model.RESULTS After PSM,the non-PSE group showed significant reductions in hospital stay,intraoperative blood loss,and operation time(all P=0.00).Multivariate analysis revealed that spleen length,portal vein diameter,splenic vein diameter,and history of PSE were independent predictive factors for IB.A nomogram predictive model of IB was constructed,and DCA demonstrated the clinical utility of this model.Both groups exhibited similar results in terms of overall survival during the follow-up period.CONCLUSION Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.
