Non-alcoholic fatty liver disease(NAFLD)is among the most frequent etiologies of cirrhosis worldwide,and it is associated with features of metabolic syndrome;the key factor influencing its prognosis is the progression...Non-alcoholic fatty liver disease(NAFLD)is among the most frequent etiologies of cirrhosis worldwide,and it is associated with features of metabolic syndrome;the key factor influencing its prognosis is the progression of liver fibrosis.This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD,analyzing the currently available literature.In the assessment of NAFLD patients,it is important to identify clinical,genetic,and environmental determinants of fibrosis development and its progression.To properly detect fibrosis,it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores,followed by a complementary imaging study(transient elastography,magnetic resonance elastography or acoustic radiation force impulse)and finally a liver biopsy,when needed.To help with the selection of the most appropriate method a Fagan′s nomogram analysis is provided in this review,describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis.Finally,treatment should always include diet and exercise,as well as controlling the components of the metabolic syndrome,+/-vitamin E,considering the presence of sleep apnea,and when available,allocate those patients with advanced fibrosis or high risk of progression into clinical trials.The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD,aiming to decrease/stop its progression and improve their prognosis.展开更多
Kartagener＇s syndrome （KS） is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia （PCD）. As it is accompanied by many complications, PCD/KS severely ...Kartagener＇s syndrome （KS） is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia （PCD）. As it is accompanied by many complications, PCD/KS severely affects the patient＇s quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.展开更多
Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β,Tau,and𝛼α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative dis...Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β,Tau,and𝛼α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD)and Parkinson’s disease(PD).In addition,various post-translational modifications(PTMs)have been identified on pathological amyloid proteins and are subjected to change during disease progression.Given the central role of amyloid proteins in NDs,tremendous efforts have been made to develop amyloid-targeting strategies for clinical diagnosis and molecular classification of NDs.In this review,we summarize two major strategies for targeting amyloid aggregates,with a focus on the trials in AD diagnosis.The first strategy is a positron emission tomography(PET)scan of protein aggregation in the brain.We mainly focus on introducing the development of small-molecule PET tracers for specifically recognizing pathological amyloid fibrils.The second strategy is the detection of PTM biomarkers on amyloid proteins in cerebrospinal fluid and plasma.We discuss the pathological roles of different PTMs in diseases and how we can use the PTM profile of amyloid proteins for clinical diagnosis.Finally,we point out the potential technical challenges of these two strategies,and outline other potential strategies,as well as a combination of multiple strategies,for molecular diagnosis of NDs.展开更多
文摘Non-alcoholic fatty liver disease(NAFLD)is among the most frequent etiologies of cirrhosis worldwide,and it is associated with features of metabolic syndrome;the key factor influencing its prognosis is the progression of liver fibrosis.This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD,analyzing the currently available literature.In the assessment of NAFLD patients,it is important to identify clinical,genetic,and environmental determinants of fibrosis development and its progression.To properly detect fibrosis,it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores,followed by a complementary imaging study(transient elastography,magnetic resonance elastography or acoustic radiation force impulse)and finally a liver biopsy,when needed.To help with the selection of the most appropriate method a Fagan′s nomogram analysis is provided in this review,describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis.Finally,treatment should always include diet and exercise,as well as controlling the components of the metabolic syndrome,+/-vitamin E,considering the presence of sleep apnea,and when available,allocate those patients with advanced fibrosis or high risk of progression into clinical trials.The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD,aiming to decrease/stop its progression and improve their prognosis.
文摘Kartagener＇s syndrome （KS） is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia （PCD）. As it is accompanied by many complications, PCD/KS severely affects the patient＇s quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(82188101,32171236,and 31872716 to C.L.,32170683 to D.L.)the Science and Technology Commission of Shanghai Municipality(STCSM)(20XD1425000 and 2019SHZDZX02 to C.L.)the Shanghai Pilot Program for Basic Research–Chinese Academy of Science,Shanghai Branch(CYJ-SHFY-2022-005)。
文摘Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β,Tau,and𝛼α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD)and Parkinson’s disease(PD).In addition,various post-translational modifications(PTMs)have been identified on pathological amyloid proteins and are subjected to change during disease progression.Given the central role of amyloid proteins in NDs,tremendous efforts have been made to develop amyloid-targeting strategies for clinical diagnosis and molecular classification of NDs.In this review,we summarize two major strategies for targeting amyloid aggregates,with a focus on the trials in AD diagnosis.The first strategy is a positron emission tomography(PET)scan of protein aggregation in the brain.We mainly focus on introducing the development of small-molecule PET tracers for specifically recognizing pathological amyloid fibrils.The second strategy is the detection of PTM biomarkers on amyloid proteins in cerebrospinal fluid and plasma.We discuss the pathological roles of different PTMs in diseases and how we can use the PTM profile of amyloid proteins for clinical diagnosis.Finally,we point out the potential technical challenges of these two strategies,and outline other potential strategies,as well as a combination of multiple strategies,for molecular diagnosis of NDs.
