Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographi...Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographic search was carried out on the use of botanical drugs,rare disease drugs,related registration management policies and regulations in PubMed and CNKI.The following keywords were searched in the database:Rare disease policies and regulations,orphan drugs,botanical drugs for intractable diseases,botanical drugs for the treatment of new coronary pneumonia,traditional Chinese medicine,and emergency guidelines for major public health crisis.Other data were obtained from“Chinese Pharmacopoeia”and relevant Chinese government websites for sorting and analysis.Results and Conclusion Based on 39 Chinese corresponding policies and regulations,challenges and opportunities of developing and researching drugs for treating rare diseases were found out after the analysis and comparison.Based on the study of national policies on drugs for rare diseases,the priority review and approval procedures in the drug registration,as well as China’s emergency guidelines and policies for major public health events,some problems in the use of drugs for rare diseases are found out.Therefore,it is recommended to actively adopt the property rights protection system,explore the folk prescriptions of traditional Chinese medicine and the potential of hospital preparations,and the registration review strategy of giving priority to the use of botanical drugs for rare diseases.Thus,the international status of botanical drugs for rare disease and the influence of responding to major public health events can be enhanced.展开更多
The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turk...The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turkey has made the relevant legal arrangements in 2020. The largest group under this common roof is “Hereditary Metabolic diseases”. The number of inherited metabolic diseases has reached a remarkable scope in the light of the rapidly accelerating developments in biochemistry, genetics, pharmacology, electronics sciences in 1902, when this name was first used, “Alkaptonuria” disease. In the light of the information obtained, 4 separate subgroups were created according to their common characteristics in order to produce solutions for this large group. Treatment options for metabolic disorders are both simple and complex. Diet therapy, cofactor therapy, enzyme replacement therapy (ERT), Substrate reduction therapy, chaperone therapy, tissue - organ - stem cell transplantation and gene therapy can be listed as these treatment options. Preimplantation genetics has been a rational solution to preventing disease formation, also supported by our ministry of health.展开更多
According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, w...According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.展开更多
Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the ...Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.展开更多
Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare.We aimed to determine health service utilization by Australian children with rare di...Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare.We aimed to determine health service utilization by Australian children with rare diseases and barriers to access-ing healthcare.Methods Parents completed an online survey on health professional and emergency department(ED)presentations,hospi-talization,and barriers to accessing services.Potential barriers to service access included residential location(city,regional,remote)and child health-related functioning,determined using a validated,parent-completed measure-of-function tool.Results Parents of 462 children with over 240 rare diseases completed the survey.Compared with the general population,these children were more likely to be hospitalized[odds ratio(OR)=17.25,95%confidence interval(CI)=15.50-19.20]and present to the ED(OR=4.15,95%CI=3.68-4.68)or a family physician(OR=4.14,95%CI=3.72-4.60).Child functional impairment was nil/mild(31%),moderate(48%)or severe(22%).Compared to children with nil/mild impair-ment,those with severe impairment were more likely to be hospitalized(OR=13.39,95%CI=7.65-23.44)and present to the ED(OR=11.16,95%CI=6.46-19.27).Most children(75%)lived in major cities,but children from regional(OR=2.78,95%CI=1.72-4.55)and remote areas(OR=9.09,95%CI=3.03-25.00)experienced significantly more barriers to healthcare access than children from major cities.Barriers included distance to travel,out-of-pocket costs,and lack of specialist medical and other health services.Conclusions Children with rare diseases,especially those with severe functional impairment have an enormous impact on health services,and better integrated multidisciplinary services with patient-centered care are needed.Access must be improved for children living in rural and remote settings.展开更多
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
The prevalence of metabolic diseases,some diseases that are seriously harmful for human health and affect the quality of life,is increasing year by year.Early detection and intervention is the common strategy to deal ...The prevalence of metabolic diseases,some diseases that are seriously harmful for human health and affect the quality of life,is increasing year by year.Early detection and intervention is the common strategy to deal with them.Infrared thermography(IRT)is a special medical imaging technology which can capture the changes of skin temperature associated with metabolic disorders.It might be a new method for early detection of metabolic diseases.The purpose of this review is to summarize advances of the use of IRT in evaluating single metabolic disorder such as obesity,hyperglycemia and hypertension,complex metabolic disorders such as metabolic syndrome and target organ damage such as coronary artery atherosclerosis and diabetic foot.The characteristic of thermograms of metabolic disease patients,the changes of thermal maps during the development of the disease,and the lacks in current studies are also discussed in the article.展开更多
Dear Editor,We present a rare case of a primary penile follicular center non-Hodgkin lymphoma and a review of the available literature on this condition.A BCL2 gene transposition which was identified with fluorescent ...Dear Editor,We present a rare case of a primary penile follicular center non-Hodgkin lymphoma and a review of the available literature on this condition.A BCL2 gene transposition which was identified with fluorescent in situ hybridization(FISH)molecular analysis is a unique manifestation not previously reported to the best of our knowledge.A 67-year-old man presented with a 3-month history of a small nodule on the left side of the corona of glans penis.The patient had no significant medical or family history.The patient underwent excision and biopsy of the penile lesion with a 0.5 cm macroscopic margin under local anesthesia and sedation.He was discharged on the day of surgery,and there were no postoperative complications or adverse events.The informed consent was obtained from thepatient.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
A hydrotalcite(layered double hydroxide, LDH) inhibitor which is suitable for the whole process of coal spontaneous combustion and a LDH inhibitor containing rare earth lanthanum elements were prepared. The inhibition...A hydrotalcite(layered double hydroxide, LDH) inhibitor which is suitable for the whole process of coal spontaneous combustion and a LDH inhibitor containing rare earth lanthanum elements were prepared. The inhibition effect and mechanism were analyzed by scanning electron microscopy(SEM),X-ray diffraction(XRD), thermal performance analysis, in-situ diffuse reflectance infrared spectroscopy and temperature-programmed experiment. The results have shown that the inhibitor containing lanthanum can play a good inhibitory role in every stage of coal oxidation. During the slow oxidation of coal samples, the inhibitor containing lanthanum ions can slow down the oxidation process of coal and increase the initial temperature of coal spontaneous combustion. At the same time, because the hydroxyl groups in LDHs are connected with-COO-groups on the coal surface through hydrogen bonds, the stability of coal is improved. With the increase of temperature, LDHs can remove interlayer water molecules and reduce the surface temperature of coal. CO release rate of coal samples decreases significantly after adding inhibitor containing lanthanum element, and the maximum inhibition rate of the inhibitor is 58.1%.展开更多
Thinning is an effective management step for sustainable forest development,yet less attention is paid to the restoration of soil microbiota after thinning.In this study,both abundant and rare soil microbial communiti...Thinning is an effective management step for sustainable forest development,yet less attention is paid to the restoration of soil microbiota after thinning.In this study,both abundant and rare soil microbial communities(i.e.,bacterial,fungal),were evaluated under various thinning treatments in a mixed stand of Cunninghamia lanceolata and Sassafras tzumu using Mi Seq sequencing.Thinning did not significantly change either abundant or rare bacterial and fungal community composition,but affected their alpha diversity.The Shannon–Wiener indexes of rare fungal taxa under medium thinning were significantly lower than in the light thinning(P<0.05 level).Xanthobacteraceae dominated the abundant bacterial taxa,and Saitozyma and Mortierlla the abundant fungal taxa.The most common rare bacterial taxa varied;there was no prevalent rare fungal taxa under different thinnings.In addition,soil available nitrogen,total phosphorus,and p H had significant effects on rare bacterial taxa.Nutrients,especially available phosphorus,but not nitrogen,affected abundant and rare soil fungi.The results indicate that soil properties rather than plant factors affect abundant and rare microbial communities in soils of mixed stands.Thinning,through mediating soil properties,influences both abundant and rare bacterial and fungal communities in the mixed C.lanceolata and S.tzumu stand.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
文摘Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographic search was carried out on the use of botanical drugs,rare disease drugs,related registration management policies and regulations in PubMed and CNKI.The following keywords were searched in the database:Rare disease policies and regulations,orphan drugs,botanical drugs for intractable diseases,botanical drugs for the treatment of new coronary pneumonia,traditional Chinese medicine,and emergency guidelines for major public health crisis.Other data were obtained from“Chinese Pharmacopoeia”and relevant Chinese government websites for sorting and analysis.Results and Conclusion Based on 39 Chinese corresponding policies and regulations,challenges and opportunities of developing and researching drugs for treating rare diseases were found out after the analysis and comparison.Based on the study of national policies on drugs for rare diseases,the priority review and approval procedures in the drug registration,as well as China’s emergency guidelines and policies for major public health events,some problems in the use of drugs for rare diseases are found out.Therefore,it is recommended to actively adopt the property rights protection system,explore the folk prescriptions of traditional Chinese medicine and the potential of hospital preparations,and the registration review strategy of giving priority to the use of botanical drugs for rare diseases.Thus,the international status of botanical drugs for rare disease and the influence of responding to major public health events can be enhanced.
文摘The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turkey has made the relevant legal arrangements in 2020. The largest group under this common roof is “Hereditary Metabolic diseases”. The number of inherited metabolic diseases has reached a remarkable scope in the light of the rapidly accelerating developments in biochemistry, genetics, pharmacology, electronics sciences in 1902, when this name was first used, “Alkaptonuria” disease. In the light of the information obtained, 4 separate subgroups were created according to their common characteristics in order to produce solutions for this large group. Treatment options for metabolic disorders are both simple and complex. Diet therapy, cofactor therapy, enzyme replacement therapy (ERT), Substrate reduction therapy, chaperone therapy, tissue - organ - stem cell transplantation and gene therapy can be listed as these treatment options. Preimplantation genetics has been a rational solution to preventing disease formation, also supported by our ministry of health.
文摘According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.
文摘Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.
基金an Australian Research Council Linkage Project grant scheme(No.LP110200277)The funding sources had no role in the study design+5 种基金in the collection,analysis and interpretation of datain the writing of the reportand in the decision to submit the paper for publication.During the period of the research,ZY held a Fellowship from the Sydney Medical School Foundation and LH was funded by a National Health and Medical Research Council of Australia Senior Research Fellowship(No.1117105)EJE was supported by a National Health and Medical Research Council of Australia Practitioner Fellowship(No.1021480)a Medical Research Futures Fund Next Generation Fellowship(No.1135959)CJ's Chair in Genomic Medicine is supported by The Royal Children's Hospital Foundation.
文摘Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare.We aimed to determine health service utilization by Australian children with rare diseases and barriers to access-ing healthcare.Methods Parents completed an online survey on health professional and emergency department(ED)presentations,hospi-talization,and barriers to accessing services.Potential barriers to service access included residential location(city,regional,remote)and child health-related functioning,determined using a validated,parent-completed measure-of-function tool.Results Parents of 462 children with over 240 rare diseases completed the survey.Compared with the general population,these children were more likely to be hospitalized[odds ratio(OR)=17.25,95%confidence interval(CI)=15.50-19.20]and present to the ED(OR=4.15,95%CI=3.68-4.68)or a family physician(OR=4.14,95%CI=3.72-4.60).Child functional impairment was nil/mild(31%),moderate(48%)or severe(22%).Compared to children with nil/mild impair-ment,those with severe impairment were more likely to be hospitalized(OR=13.39,95%CI=7.65-23.44)and present to the ED(OR=11.16,95%CI=6.46-19.27).Most children(75%)lived in major cities,but children from regional(OR=2.78,95%CI=1.72-4.55)and remote areas(OR=9.09,95%CI=3.03-25.00)experienced significantly more barriers to healthcare access than children from major cities.Barriers included distance to travel,out-of-pocket costs,and lack of specialist medical and other health services.Conclusions Children with rare diseases,especially those with severe functional impairment have an enormous impact on health services,and better integrated multidisciplinary services with patient-centered care are needed.Access must be improved for children living in rural and remote settings.
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.
基金Special Fund for Basic Scientific Research of Central Universities(2020-JYB-ZDGG-117)。
文摘The prevalence of metabolic diseases,some diseases that are seriously harmful for human health and affect the quality of life,is increasing year by year.Early detection and intervention is the common strategy to deal with them.Infrared thermography(IRT)is a special medical imaging technology which can capture the changes of skin temperature associated with metabolic disorders.It might be a new method for early detection of metabolic diseases.The purpose of this review is to summarize advances of the use of IRT in evaluating single metabolic disorder such as obesity,hyperglycemia and hypertension,complex metabolic disorders such as metabolic syndrome and target organ damage such as coronary artery atherosclerosis and diabetic foot.The characteristic of thermograms of metabolic disease patients,the changes of thermal maps during the development of the disease,and the lacks in current studies are also discussed in the article.
文摘Dear Editor,We present a rare case of a primary penile follicular center non-Hodgkin lymphoma and a review of the available literature on this condition.A BCL2 gene transposition which was identified with fluorescent in situ hybridization(FISH)molecular analysis is a unique manifestation not previously reported to the best of our knowledge.A 67-year-old man presented with a 3-month history of a small nodule on the left side of the corona of glans penis.The patient had no significant medical or family history.The patient underwent excision and biopsy of the penile lesion with a 0.5 cm macroscopic margin under local anesthesia and sedation.He was discharged on the day of surgery,and there were no postoperative complications or adverse events.The informed consent was obtained from thepatient.
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Funded by National Natural Science Foundation of China (No.52074218)。
文摘A hydrotalcite(layered double hydroxide, LDH) inhibitor which is suitable for the whole process of coal spontaneous combustion and a LDH inhibitor containing rare earth lanthanum elements were prepared. The inhibition effect and mechanism were analyzed by scanning electron microscopy(SEM),X-ray diffraction(XRD), thermal performance analysis, in-situ diffuse reflectance infrared spectroscopy and temperature-programmed experiment. The results have shown that the inhibitor containing lanthanum can play a good inhibitory role in every stage of coal oxidation. During the slow oxidation of coal samples, the inhibitor containing lanthanum ions can slow down the oxidation process of coal and increase the initial temperature of coal spontaneous combustion. At the same time, because the hydroxyl groups in LDHs are connected with-COO-groups on the coal surface through hydrogen bonds, the stability of coal is improved. With the increase of temperature, LDHs can remove interlayer water molecules and reduce the surface temperature of coal. CO release rate of coal samples decreases significantly after adding inhibitor containing lanthanum element, and the maximum inhibition rate of the inhibitor is 58.1%.
基金the Sino-German Cooperation Forestry Major Scientific Research Project(zdczhz2021ky09)the National Natural Science Foundation of China(31971487 and 42277245).
文摘Thinning is an effective management step for sustainable forest development,yet less attention is paid to the restoration of soil microbiota after thinning.In this study,both abundant and rare soil microbial communities(i.e.,bacterial,fungal),were evaluated under various thinning treatments in a mixed stand of Cunninghamia lanceolata and Sassafras tzumu using Mi Seq sequencing.Thinning did not significantly change either abundant or rare bacterial and fungal community composition,but affected their alpha diversity.The Shannon–Wiener indexes of rare fungal taxa under medium thinning were significantly lower than in the light thinning(P<0.05 level).Xanthobacteraceae dominated the abundant bacterial taxa,and Saitozyma and Mortierlla the abundant fungal taxa.The most common rare bacterial taxa varied;there was no prevalent rare fungal taxa under different thinnings.In addition,soil available nitrogen,total phosphorus,and p H had significant effects on rare bacterial taxa.Nutrients,especially available phosphorus,but not nitrogen,affected abundant and rare soil fungi.The results indicate that soil properties rather than plant factors affect abundant and rare microbial communities in soils of mixed stands.Thinning,through mediating soil properties,influences both abundant and rare bacterial and fungal communities in the mixed C.lanceolata and S.tzumu stand.
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.
