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Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease *** on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom *** 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for *** Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the *** muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal *** accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real *** advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and *** technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of *** are two major goals of this *** first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activi

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

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Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

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World Journal of Gastroenterology 2024年第10期30卷 1295-1312页

作者： Hui Ma Qing-Zhu Yan Jing-Ru Ma Dong-Fu Li Jun-Ling Yang Department of Clinical Laboratory The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Ultrasound Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Digestive diseases Center Department of Hepatopancreatobiliary MedicineThe Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Department of Respiratory and Critical Care Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease *** review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and *** delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive *** factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are ***,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease *** reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is *** strategies,including anti-viral and immunomodulatory approaches,are critically *** role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent *** conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV *** a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge *** more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient *** dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory *** role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

关键词： Hepatitis B virus reactivation Immunological mechanisms disease progression Management strategies Immune response

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Neuroflament light and heterogeneity of disease progression in amyotrophic lateral sclerosis:development and validation of a prediction model to improve interventional trials

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Translational Neurodegeneration 2021年第3期10卷 400-411页

作者： Simon Witzel Felix Frauhammer† Petra Steinacker David Devos Pierre‑François Pradat Vincent Meininger Stefen Halbgebauer Patrick Oeckl Joachim Schuster Simon Anders Johannes Dorst Markus Otto Albert C.Ludolph Department of Neurology University of UlmUlmGermany Center for Molecular Biology Heidelberg UniversityHeidelbergGermany Depart‑ment of Medical Pharmacology Expert center for ParkinsonCHU‑LilleLille Neuroscience and CognitionInsermUMR‑S1172LICENDNS‑Park NetworkUniversity of LilleLilleFrance Laboratoire D’Imagerie Biomédicale Sorbonne UniversitéCNRSINSERMParisFrance APHP Département de NeurologieHôpital Pitié-SalpêtrièreParisFrance German Centre for Neurodegenerative diseases(DZNE)Site Ulm UlmGermany

Background:Interventional trials in amyotrophic lateral sclerosis(ALS)sufer from the heterogeneity of the disease as it considerably reduces statistical *** asked if blood neuroflament light chains(NfL)could be used to antici‑pate disease progression and increase trial ***:In 125 patients with ALS from three independent prospective studies-one observational study and two interventional trials-we developed and externally validated a multivariate linear model for predicting disease pro‑gression,measured by the monthly decrease of the ALS Functional Rating Scale Revised(ALSFRS-R)*** trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis:NfL levels,sex,age,site of onset,body mass index,disease duration,ALSFRS-R score,and monthly ALSFRS-R score decrease since disease *** then applied the resulting model in the other two study cohorts to assess the actual utility for interventional *** analyzed the impact on trial power in mixed-efects models and compared the performance of the NfL model with two currently used predictive approaches,which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period(lead-in)or since disease onset(ΔFRS).Results:Among the parameters provided,the NfL levels(P<0.001)and the interaction with site of onset(P<0.01)contributed signifcantly to the prediction,forming a robust NfL prediction model(R=0.67).Model application in the trial cohorts confrmed its applicability and revealed superiority over lead-in andΔFRS-based *** NfL model improved statistical power by 61%and 22%(95%confdence intervals:54%-66%,7%-29%).Conclusion:The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could signif‑cantly increase the trial ***00868166,registered March23,2009;NCT02306590,registered December 2,2014.

关键词： Neuroflament light Prediction model disease progression Amyotrophic lateral sclerosis Interventional trials Statistical power

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Hypothetical hypoxia-driven rapid disease progression in hepatocellular carcinoma post transarterial chemoembolization:A case report

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World Journal of Clinical Cases 2023年第19期11卷 4664-4669页

作者： Kai-Fuan Yeo Amy Ker Pei-En Kao Chi-Chih Wang Division of Gastroenterology and Hepatology Department of Internal MedicineChung Shan Medical University HospitalTaichung 402306Taiwan China School of Medicine Chung Shan Medical UniversityTaichung 402306TaiwanChina

BACKGROUND Transarterial chemoembolization(TACE)is widely performed for intermediatestage or unresectable hepatocellular carcinoma(HCC),but approximately half of patients do not respond to TACE *** describe a case of rapidly progressing of HCC after TACE and provide a possible hypothesis for this *** finding may contribute to identifying patients who obtain less benefit from TACE,thus avoiding the unnecessary waste of medical resources and treatment during the golden hour *** SUMMARY A 61-year-old woman had been diagnosed with chronic hepatitis B infection and HCC at Barcelona Clinic Liver Cancer stage B,which had been treated by segmental hepatectomy 14 mo *** tumor recurred in the two months after *** received an initial TACE and then underwent systemic therapy with lenvatinib 8 mg daily due to an increased level of alpha-fetoprotein(AFP)after the first ***,the tumor continued to progress with an increased level of AFP,and she underwent a second TACE,after which the tumor volume did not obviously decrease on the contrast-enhanced computed tomography *** month later,she had a third TACE to control the residual HCC *** weeks after that,the HCC had increased dramatically with tea-colored urine and yellowish skin ***,the patient refused further treatment and went into hospice *** Intense hypoxia induced by TACE can trigger rapid disease progression in infiltrative HCC patients with a large tumor burden.

关键词： Carcinoma hepatocellular Transarterial chemoembolization Tumor hypoxia disease progression Tumor burden Case report

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Prediction for risk of disease progression among hospitalized COVID-19 patients

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Medical Data Mining 2023年第2期6卷 41-49页

作者： Jia-Shu Shen Qing-Qing Yang Qiao-Xin Shi Hou-Yu Zhao Lin Zhuo Hai-Bo Song Yun Lu Si-Yan Zhan Hong Cheng Feng Sun Department of School of Public Health Peking University Health Science CenterBeijing 100191China Department of Research Center of Clinical Epidemiology Peking University Third HospitalBeijing 100191China Department of Pharmacovigilance National Center for ADR MonitoringBeijing 100191China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430000China

Objective:The COVID-19 pandemic poses a significant threat to global *** the lack of studies on risk factors for COVID-19 progression at present,this study aimed to build a predictive model to predict the progression risk among hospitalized COVID-19 ***:We extracted data from 1074 mild and moderate COVID-19 patients from Electronic Health Records(EHRs)in a designated Wuhan hospital including demographic characteristics and clinical and laboratory *** progression was defined as progressing to severe critical illness after *** LASSO regression was used to select the predicted variables and a logistic regression model was applied to build the predictive *** was used to show the ***:Seven variables were included in the predictive model:age per 10 years(OR,1.15;95%CI,1.03-1.29),lactate dehydrogenase(OR,1.73;95%CI,1.14-2.62),neutrophil-to-lymphocyte ratio(OR,2.07;95%CI,1.42-3.02),eosinophil count(OR,2.10;95%CI,1.20-3.69),albumin(OR,2.37;95%CI,1.65-3.45),hemoglobin(OR,1.50;95%CI,1.10-2.05),D-dimer(OR,1.63;95%CI,1.19-2.23).The mean area under the receiver operating characteristic curve of the predictive model was 0.72(95%CI,0.69-0.76).Conclusions:This study built a predictive model that could effectively predict the progression risk among hospitalized COVID-19 patients.

关键词： coronavirus disease 2019(COVID-19) predictive model disease progression

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Comparison of cognitive and UHDRS measures in monitoring disease progression in Huntington’s disease: a 12-month longitudinal study

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Translational Neurodegeneration 2014年第1期3卷 109-118页

作者： Eng A Toh Michael R MacAskill John C Dalrymple-Alford Daniel J Myall Leslie Livingston Sandy AD Macleod Tim J Anderson Department of Medicine Christchurch School of Medicine&Health SciencesUniversity of OtagoChristchurchNew Zealand New Zealand Brain Research Institute ChristchurchNew Zealand Department of Psychology University of CanterburyChristchurchNew Zealand Brain Injury Rehabilitation Service Canterbury District Health BoardChristchurchNew Zealand Department of Neurology Canterbury District Health BoardChristchurchNew Zealand

Progressive cognitive decline is a feature of Huntington’s disease(HD),an inherited neurodegenerative movement *** neuropsychological testing is the‘gold standard’to establish cognitive status but is often impractical in time-constrained *** study evaluated the utility of brief cognitive tests(MMSE and MoCA),UHDRS measures and a comprehensive neuropsychological tests battery in monitoring short-term disease progression in ***-two manifest HD patients and 22 matched controls were assessed at baseline and 12-month.A linear mixed-effect model showed that although the HD group had minimal change in overall global cognition after 12 months,they did show a significant decline relative to the control *** controls exhibited a practice effect in most of the cognitive domain scores over *** decline at 12-month in HD was found in the executive function domain but the effect of this on global cognitive score was masked by the improvement in their language domain *** varying practice effects by cognitive domain with repeated testing indicates the importance of comparing HD patients to control group in research trials and that cognitive progression over 12 months in HD should not be judged by changes in global cognitive *** three brief cognitive tests effectively described cognition of HD patients on cross-sectional *** UHDRS cognitive component,which focuses on testing executive function and had low variance over time,is a more reliable brief substitute for comprehensive neuropsychological testing than MMSE and MoCA in monitoring cognitive changes in HD patients after 12 months.

关键词： Huntington’s disease disease progression Cognition UHDRS Longitudinal

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RDW is associated with disease progression in patients with chronic HBV liver disease

RDW is associated with disease progression in patients with ...

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第十一届全国免疫学学术大会

作者： Yang kai Guan Shihe Zhou Qiang Pan Ying Wu Yuanyuan Wang Aihua Sun Beibei Zhang Hao Department of Clinical Laboratory the Second Affiliated Hospital of Anhui Medical University

Background: Hepatitis B virus(HBV) infection is a major threat to human health worldwide, especially to people living in China. This study aimed to evaluate clinical significance of red blood cell distribution as a potential indicator to monitor disease progression in patients with HBV-related liver ***: A total of 731 individuals with HBV-related liver disease, comprising 92 patients with Chronic HBV infection(CHB), 606 patients with liver cirrhosis after HBV infection and 33 patients with hepatocellular carcinoma after HBV infection.50 healthy volunteers represented the control cohort. Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Alkaline phosphatase(ALP), Total bilirubin(Tbil), Albumin(Alb), Creatinine(CRE), Prothrombin time(PT),Hemoglobin(Hb), Erythrocyte mean corpuscular volume(MCV), Platelet(PLT) and Red blood cell distribution width(RDW) were tested and monitored with development of HBV-related liver disease at different stages. We compared RDW with ALT, AST, ALP, Tbil, Albumin, CRE, PT, Hb, MCV, PLT parameters. By receiver operating characteristic(ROC) analysis,the sensitivity and specificity of RDW was estimated in identifying the disease progression in patients with HBV-related liver disease. Results: Our results showed that RDW was significantly increased in patients with HBV-related liver disease. Moreover,RDW was positively correlated with AST, ALP, Tbil and PT levels, and negatively correlated with Alb, Hb, MCV and platelet counts. Among the patients with decompensated liver cirrhosis, RDW increased with worsening of Child-Pugh grade. ROC curve showed RDW to be the most significant marker as an indicator of patients with CHB who develop into compensated liver cirrhosis. Also, the same analysis for patients had liver cirrhosis with decompensation indicated RDW to be the most sensitive and specific parameter. Conclusions: RDW in patients with HBV-related liver disease is a useful indicator to predict disease progression.

关键词： Red blood cell distribution width Hepatitis B virus disease progression

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RDW is associated with disease progression in patients with chronic HBV liver disease

RDW is associated with disease progression in patients with ...

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第十三届全国免疫学学术大会

作者：杨凯安徽医科大学第二附属医院

Background: This study aimed to evaluate clinical significance of RDW as a potential indicator to monitor disease progression in patients with HBV-related liver ***: ALT, AST, ALP, Tbil, Alb, CRE, PT, Hb, MCV, PLT and RDW were tested and monitored with development of HBV-related liver *** compared RDW with other *** sensitivity and specificity of RDW was estimated in identifying the disease progression in ***: Our results showed that RDW was significantly increased in patients with HBV-related liver *** was positively correlated with AST, ALP, Tbil and PT levels, and negatively correlated with Alb, Hb, MCV and *** the patients with DLC, RDW increased with worsening of Child-Pugh *** curve showed RDW to be the most significant marker as an indicator of CHB patients who develop into compensated liver ***, the same analysis for patients had liver cirrhosis with decompensation indicated RDW to be the most sensitive and specific ***: RDW in patients with HBV-related liver disease is a useful indicator to predict disease progression.

关键词： Red blood cell distribution width Hepatitis B virus disease progression

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Association of serum uric acid levels with the progression of Parkinson＇s disease in Chinese patients

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Chinese Medical Journal 2012年第4期000卷 583-587页

作者： Sun Cong-cong Luo Fei-fei Wei Lei Lei Mi Li Guo-fei Liu Zhuo-lin Le Wei-dong Xu Ping-yi Sun Yat Sen Univ Affiliated Hosp 1 Dept Neurol Guangzhou 510080 Guangdong Peoples R China Henan Univ Huaihe Hosp Dept Neurol Kaifeng 47500 Henan Peoples R China Baylor Coll Med Dept Neurol Houston TX 77030 USA Shanghai Jiao Tong Univ Sch Med Shanghai 200025 Peoples R China Chinese Acad Sci Inst Biol Sci Inst Hlth Sci Key Lab Stem Cell Biol Shanghai 200025 Peoples R China

Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese *** Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method,the serum creatinine （Scr） levels were also measured to reduce the bias caused by possible differences in renal excretion *** disease progression was scored by Hoehn and Yahr （H＆Y） scales and disease durations; PD group was divided into 3 subgroups according to H＆Y ***-samples ttest was performed to analyze the differences between PD group and control *** analysis of covariance was performed to analyze the differences between PD *** rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease *** PD patients were found to have significantly lower levels of serum UA than controls （（243.38±78.91） vs.（282.97±90.80） pmol/L,P〈0.01）.As the disease progression,the serum UA levels were gradually *** was a significantly inverse correlation of UA levels with H＆Y scales （Rs=-0.429,P 〈0.01） and disease duration （Rs=-0.284,P 〈0.01） in PD patients of both females and *** significant difference of the Scr level between PD patients and controls was found （（70.01±14.70） vs.（69.84±16.46） μmol/L）,and the Scr level was not involved in disease *** Lower serum UA levels may possess a higher risk of PD,which may be a potential useful biomarker to indicate the progression of PD.

关键词： uric acid Parkinson's disease disease progression

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