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 This study evaluated the safety and effectiveness of endoscopic retrograde cholangiopancreatography(ERCP)in pediatric patients with biliary and pancreatic diseases.A retrospective analysis was conducted on ...BACKGROUND This study evaluated the safety and effectiveness of endoscopic retrograde cholangiopancreatography(ERCP)in pediatric patients with biliary and pancreatic diseases.A retrospective analysis was conducted on 57 ERCP procedures performed in 41 children,primarily for treating pancreatic diseases.The overall success rate was 91.2%,with no major complications observed.Post-ERCP pancreatitis(PEP)occurred in 8.8%of cases.Follow-up examinations over one year showed no recurrence of biliary or pancreatic diseases.Notably,endoscopic treatment led to a significant increase in body mass index(BMI).These findings demonstrate the valuable role of ERCP in managing such conditions.AIM To evaluate the safety and efficacy of ERCP for the management of biliary and pancreatic diseases in pediatric patients.METHODS We conducted a retrospective analysis of data from children aged 1-18 years who underwent ERCP for biliary and pancreatic diseases at Beijing Children’s Hospital between January 2021 and December 2022.The collected data included procedure time,endoscopic treatment,success rate,and postoperative complications.RESULTS Forty-one children underwent 57 ERCP procedures,including 14 with biliary duct disease and 27 with pancreatic disease.The mean age of the patients was 7.48±3.48 years.Biliary duct-related treatments were performed 18 times,and pancreatic disease treatments were performed 39 times.ERCP was primarily used to treat pediatric pancreatic diseases[68.4%(39/57)of the procedures].The overall success rate was 91.2%(52/57 patients).PEP was noted in five patients(8.8%,5/57),and no instances of bleeding,perforation,or cholangitis were observed.The patients were followed up for over one year,and no recurrence of biliary or pancreatic diseases was detected.Importantly,BMI significantly increased after endoscopic treatment compared to that before treatment(P=0.001).CONCLUSION The high success rate and lack of major complications support the valuable role of ERCP in the management of pediatric biliary and pancreatic diseases in the pediatric population.展开更多
BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe in...BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.展开更多
Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD dev...Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.展开更多
In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nu...In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nursing domain of basic nursing education. The purpose of this research is to examine the current status of bioethics education in the pediatric nursing domain of basic nursing education and explore the challenges perceived by the pediatric nursing faculty regarding bioethics education. The research method was a questionnaire survey on 100 randomly selected pediatric nursing faculty members from nursing universities across Japan. The results revealed that although bioethics issues were considered important, the emphasis remained primarily on addressing bioethics as part of nursing that respects children’s rights. Furthermore, respondents expressed difficulties regarding teaching methods and content related to bioethics.展开更多
There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult p...There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.展开更多
Pediatric inflammatory bowel disease(IBD)is a chronic inflammatory disorder,with increasing incidence and prevalence worldwide.There have been recent advances in imaging and endoscopic technology for disease diagnosis...Pediatric inflammatory bowel disease(IBD)is a chronic inflammatory disorder,with increasing incidence and prevalence worldwide.There have been recent advances in imaging and endoscopic technology for disease diagnosis,treatment,and monitoring.Intestinal ultrasound,including transabdominal,transperineal,and endoscopic,has been emerging for the assessment of transmural bowel inflammation and disease complications(e.g.,fistula,abscess).Aside from surgery,IBD-related intestinal strictures now have endoscopic treatment options including through-the-scope balloon dilatation,injection,and needle knife stricturotomy and new evaluation tools such as endoscopic functional lumen imaging probe.Unsedated transnasal endoscopy may have a role in patients with upper gastrointestinal Crohn’s disease or those with IBD with new upper gastrointestinal symptoms.Improvements to dysplasia screening in pediatric patients with longstanding colonic disease or primary sclerosing cholangitis hold promise with the addition of virtual chromoendoscopy and ongoing research in the field of artificial intelligence-assisted endoscopic detection.Artificial intelligence and machine learning is a rapidly evolving field,with goals of further personalizing IBD diagnosis and treatment selection as well as prognostication.This review summarized these advancements,focusing on pediatric patients with IBD.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
Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to...Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.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
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 This study evaluated the safety and effectiveness of endoscopic retrograde cholangiopancreatography(ERCP)in pediatric patients with biliary and pancreatic diseases.A retrospective analysis was conducted on 57 ERCP procedures performed in 41 children,primarily for treating pancreatic diseases.The overall success rate was 91.2%,with no major complications observed.Post-ERCP pancreatitis(PEP)occurred in 8.8%of cases.Follow-up examinations over one year showed no recurrence of biliary or pancreatic diseases.Notably,endoscopic treatment led to a significant increase in body mass index(BMI).These findings demonstrate the valuable role of ERCP in managing such conditions.AIM To evaluate the safety and efficacy of ERCP for the management of biliary and pancreatic diseases in pediatric patients.METHODS We conducted a retrospective analysis of data from children aged 1-18 years who underwent ERCP for biliary and pancreatic diseases at Beijing Children’s Hospital between January 2021 and December 2022.The collected data included procedure time,endoscopic treatment,success rate,and postoperative complications.RESULTS Forty-one children underwent 57 ERCP procedures,including 14 with biliary duct disease and 27 with pancreatic disease.The mean age of the patients was 7.48±3.48 years.Biliary duct-related treatments were performed 18 times,and pancreatic disease treatments were performed 39 times.ERCP was primarily used to treat pediatric pancreatic diseases[68.4%(39/57)of the procedures].The overall success rate was 91.2%(52/57 patients).PEP was noted in five patients(8.8%,5/57),and no instances of bleeding,perforation,or cholangitis were observed.The patients were followed up for over one year,and no recurrence of biliary or pancreatic diseases was detected.Importantly,BMI significantly increased after endoscopic treatment compared to that before treatment(P=0.001).CONCLUSION The high success rate and lack of major complications support the valuable role of ERCP in the management of pediatric biliary and pancreatic diseases in the pediatric population.
文摘BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.
文摘Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.
文摘In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nursing domain of basic nursing education. The purpose of this research is to examine the current status of bioethics education in the pediatric nursing domain of basic nursing education and explore the challenges perceived by the pediatric nursing faculty regarding bioethics education. The research method was a questionnaire survey on 100 randomly selected pediatric nursing faculty members from nursing universities across Japan. The results revealed that although bioethics issues were considered important, the emphasis remained primarily on addressing bioethics as part of nursing that respects children’s rights. Furthermore, respondents expressed difficulties regarding teaching methods and content related to bioethics.
基金Division of Neurology,Cincinnati Children’s Hospital Medical Center(as a Medical Student Scholars Program award to ALM)。
文摘There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.
文摘Pediatric inflammatory bowel disease(IBD)is a chronic inflammatory disorder,with increasing incidence and prevalence worldwide.There have been recent advances in imaging and endoscopic technology for disease diagnosis,treatment,and monitoring.Intestinal ultrasound,including transabdominal,transperineal,and endoscopic,has been emerging for the assessment of transmural bowel inflammation and disease complications(e.g.,fistula,abscess).Aside from surgery,IBD-related intestinal strictures now have endoscopic treatment options including through-the-scope balloon dilatation,injection,and needle knife stricturotomy and new evaluation tools such as endoscopic functional lumen imaging probe.Unsedated transnasal endoscopy may have a role in patients with upper gastrointestinal Crohn’s disease or those with IBD with new upper gastrointestinal symptoms.Improvements to dysplasia screening in pediatric patients with longstanding colonic disease or primary sclerosing cholangitis hold promise with the addition of virtual chromoendoscopy and ongoing research in the field of artificial intelligence-assisted endoscopic detection.Artificial intelligence and machine learning is a rapidly evolving field,with goals of further personalizing IBD diagnosis and treatment selection as well as prognostication.This review summarized these advancements,focusing on pediatric patients with IBD.
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.
文摘Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.
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.
