Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data ...Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.展开更多
BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and pre...BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and prevention.Although genetic andenvironmental factors have been widely studied,the role of lifestyle factors suchas physical activity,diet,smoking,sleep,and stress remains underexplored,especially in patients with early stage CRC or polyps.Recent evidence suggeststhat lifestyle behaviors may influence cancer progression by modulating inflammatorypathways,metabolic health,and immune function.For instance,highlevels of physical activity are linked to a reduced risk of CRC development,whereas poor dietary habits,smoking,and inadequate sleep have all beenimplicated in increased cancer risk and progression.Moreover,early-stage CRCpatients,who are often asymptomatic or have minimal symptoms,may particularlybenefit from lifestyle modifications to slow disease progression andimprove overall prognosis.The gap in understanding the specific influence ofthese lifestyle factors on colorectal polyps and early stage cancer progressionunderscores the need for comprehensive studies.By assessing several modifiablelifestyle factors and their association with disease progression,clinicians canidentify practical intervention points.These interventions could ultimately reducethe need for more aggressive treatments and improve the long-term outcomes inaffected patients.AIMTo investigate the association between lifestyle factors and disease progression inpatients with colorectal polyps and early stage cancer.METHODSIn this observational study conducted from January 2022 to December 2023,werecruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital.Lifestyle factors,including physical activity,dietary patterns,smoking status,sleep quality,andstress levels,were assessed using validated questionnaires.Disease progression was evaluated using standardizedfollow-up colonoscopies and pathological examinations.Cox proportional hazards models were used to analyzethe association between lifestyle factors and disease progression after adjusting for potential confounders.RESULTSDuring the median follow-up of 18.4 months,42(35.0%)patients experienced disease progression.High levels ofphysical activity were associated with reduced progression risk[adjusted hazard ratio(HR)0.55,95%confidenceinterval(CI):0.38-0.80,P=0.002]compared to low activity levels.High adherence to a healthy dietary patternshowed similar protective effects(adjusted HR 0.62,95%CI:0.43-0.89,P=0.009).Current smoking(adjusted HR1.92,95%CI:1.35-2.73,P<0.001)and poor sleep quality(adjusted HR 1.38,95%CI:1.05-1.82,P=0.021)wereassociated with increased progression risk.The impact of lifestyle factors was particularly pronounced in patientsyounger than 60 years and those with multiple polyps at baseline.CONCLUSIONThis study demonstrated significant associations between lifestyle factors and disease progression in colorectalpolyps and early stage cancer.Physical activity,dietary patterns,smoking status,and sleep quality have emergedas key modifiable factors influencing disease progression.These findings support the integration of lifestyleassessments and modifications in the clinical management of patients with colorectal neoplasia.展开更多
This study aims to understand the current status of fear of disease progression(FoP)in patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI),and to explore the relationship between...This study aims to understand the current status of fear of disease progression(FoP)in patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI),and to explore the relationship between FoP levels,perceived control,and medical coping strategies in these patients.A total of 360 CHD patients who underwent PCI at Xijing Hospital in Shaanxi Province between June and November 2024 were selected using a convenience sampling method.Surveys included a general information questionnaire,the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the revised Control Attitudes Scale(CAS-R),and the Medical Coping Modes Questionnaire(MCMQ).Pearson correlation analysis was used to examine the relationships between disease perception,positive coping strategies,and FoP.A total of 360 patients completed the study.The average score for FoP in patients with CHD after PCI was 31.64±4.61.FoP was negatively correlated with perceived control(r=-0.106,P<0.01)and medical coping(r=-0.194,P<0.01).Multivariate regression analysis showed that the type of intervention,family history of CHD,smoking status,perceived control,and total medical coping score were significant factors influencing FoP(P<0.01).Enhancing perceived control and identifying positive coping strategies can improve FoP levels in patients with CHD after PCI.Therefore,clinicians should focus on perceived control and medical coping levels in patients and develop targeted interventions to alleviate negative emotions related to FoP.展开更多
Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With 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 base.The 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 outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The 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.展开更多
BACKGROUND The mental well-being of individuals with coronary heart disease(CHD)during the intensive care unit(ICU)transition period is a multifaceted and significant concern.In this phase,the individuals might encoun...BACKGROUND The mental well-being of individuals with coronary heart disease(CHD)during the intensive care unit(ICU)transition period is a multifaceted and significant concern.In this phase,the individuals might encounter psychological challenges like anxiety and depression,which can impede their recuperation and potentially have lasting effects on their health.AIM To investigate the correlation among psychological factors in CHD patients in the ICU transition period.METHODS A questionnaire survey was conducted with 119 patients admitted to the ICU after coronary artery bypass grafting between March and December 2023.Variations in Hamilton Anxiety Scale(HAMA)and Hamilton Depression Scale(HAMD),Fear of Progression Questionnaire-Short Form(Fop-Q-SF),and Social Support Rating Scale(SSRS)were collected and analyzed among diverse populations.We used Pearson’s correlation analysis to examine the correlation.Multiple linear regression analysis was used to explore whether these indicators influenced depression and anxiety in the patients.RESULTS The total scores for anxiety,depression,fear of disease progression,and social support were(7.50±1.41)points,(8.38±1.62)points,(35.19±8.14)points,and(36.34±7.08)points,respectively(P<0.05).Multivariate regression analysis showed that both the level of disease progression and social support affected the level of postoperative depression and anxiety in patients.CONCLUSION The anxiety and depression levels were positively related to each dimension of phobia disease progression and negatively related to each dimension of social support among patients with CHD.展开更多
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based 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 onset.Since 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 regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal 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 phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The 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 metabolites.This 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 disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic ...Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates：a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.展开更多
Multiple Sclerosis（MS） is a major cause of neurological disability in adults and has an annual cost of approximately $28 billion in the United States. MS is a very complex disorder as demyelination can happen in a v...Multiple Sclerosis（MS） is a major cause of neurological disability in adults and has an annual cost of approximately $28 billion in the United States. MS is a very complex disorder as demyelination can happen in a variety of locations throughout the brain; therefore, this disease is never the same in two patients making it very hard to predict disease progression. A modeling approach which combines clinical, biological and imaging measures to help treat and fight this disorder is needed. In this paper, I will outline MS as a very heterogeneous disorder, review some potential solutions from the literature, demonstrate the need for a biomarker and will discuss how computational modeling combined with biological, clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism.展开更多
Compensatory/adaptive mechanisms in the brain are hy- pothesized to be involved in its protection from the Alz- heimer＇s disease （AD） progression. These mechanisms are activated by malfunctioning of various brain s...Compensatory/adaptive mechanisms in the brain are hy- pothesized to be involved in its protection from the Alz- heimer＇s disease （AD） progression. These mechanisms are activated by malfunctioning of various brain systems： anti- oxidant, neurotrophic, neurotransmitter, immune, and oth- ers. Detailed analysis of compensatory^adaptive capabilities of these systems might be a start point for further discovery and development of perspective approaches for early diag- nostics and treatment of AD and associated neurodegenera- tive disorders.展开更多
BACKGROUND Transarterial chemoembolization(TACE)is widely performed for intermediatestage or unresectable hepatocellular carcinoma(HCC),but approximately half of patients do not respond to TACE treatment.We describe a...BACKGROUND Transarterial chemoembolization(TACE)is widely performed for intermediatestage or unresectable hepatocellular carcinoma(HCC),but approximately half of patients do not respond to TACE treatment.We describe a case of rapidly progressing of HCC after TACE and provide a possible hypothesis for this condition.The 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 window.CASE 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 ago.The tumor recurred in the two months after surgery.She 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 TACE.However,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 image.One month later,she had a third TACE to control the residual HCC tumors.Two weeks after that,the HCC had increased dramatically with tea-colored urine and yellowish skin turgor.Eventually,the patient refused further treatment and went into hospice care.CONCLUSION Intense hypoxia induced by TACE can trigger rapid disease progression in infiltrative HCC patients with a large tumor burden.展开更多
Objective:The COVID-19 pandemic poses a significant threat to global health.Given the lack of studies on risk factors for COVID-19 progression at present,this study aimed to build a predictive model to predict the pro...Objective:The COVID-19 pandemic poses a significant threat to global health.Given 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 patients.Methods: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 information.Disease progression was defined as progressing to severe critical illness after admission.The LASSO regression was used to select the predicted variables and a logistic regression model was applied to build the predictive model.Nomogram was used to show the results.Results: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.展开更多
Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer ...Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer of a cancer hospital in Tianjin were selected as the research objects by the convenience sampling method.The general data questionnaire,spouse fear of disease progression scale and self-efficacy scale were used to investigate.Multiple linear regression was used to analyze the influencing factors of the fear of the disease progression in the postoperative pa tients’spouse of bladder cancer.Results:The score of fear of disease progression was(35.75±9.86).The results of multiple linear regression analysis showed that the spouse’s age,medical payment method,occupational status and self-efficacy were the main influencing factors for the spouse’s fear of disease progression after bladder cancer(P<0.05),which accounted for 55%of the total variation.Conclusion:The spouse’s fear of disease progression in patients with bladder cancer is at a moderate lev el,and age,medical payment method,occupational status and self-efficacy are the main influencing factors.It is suggested that clinical medical staff focus on young,rural cooperative medical care,self-financed,in-service,and unemployed,low self-eff icacy of postoperative bladder cancer patients'spouses.A series of psychological counseling and health education should be given to help the patient spouse correctly understand and deal with diseases,reduce the patients’spouses of negative emotions,im prove the patients’spouses of self-efficacy,and reduce the spouse fear level of disease progression.展开更多
Objective To use high-throughput transcriptome sequencing data to screen for a set of non-invasive diagnostic biomarkers for assessing the risk of pulmonary tuberculosis(PTB)and predicting disease progression stages.M...Objective To use high-throughput transcriptome sequencing data to screen for a set of non-invasive diagnostic biomarkers for assessing the risk of pulmonary tuberculosis(PTB)and predicting disease progression stages.Methods A total of 37 effective microarray transcriptome datasets were collected from the National Center for Biotechnology Information(NCBI)from January 2015 to December 2024,covering five groups:control group,PTB group,extrapulmonary TB(EPTB)group,latent TB infection(LTBI)group,and other diseases(OD)group.展开更多
Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not...Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).展开更多
Background:Interventional trials in amyotrophic lateral sclerosis(ALS)sufer from the heterogeneity of the disease as it considerably reduces statistical power.We asked if blood neuroflament light chains(NfL)could be u...Background:Interventional trials in amyotrophic lateral sclerosis(ALS)sufer from the heterogeneity of the disease as it considerably reduces statistical power.We asked if blood neuroflament light chains(NfL)could be used to antici‑pate disease progression and increase trial power.Methods: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)score.We 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 onset.We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials.We 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 approaches.The 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 power.NCT00868166,registered March23,2009;NCT02306590,registered December 2,2014.展开更多
Progressive cognitive decline is a feature of Huntington’s disease(HD),an inherited neurodegenerative movement disorder.Comprehensive neuropsychological testing is the‘gold standard’to establish cognitive status bu...Progressive cognitive decline is a feature of Huntington’s disease(HD),an inherited neurodegenerative movement disorder.Comprehensive neuropsychological testing is the‘gold standard’to establish cognitive status but is often impractical in time-constrained clinics.The 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 HD.Twenty-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 group.The controls exhibited a practice effect in most of the cognitive domain scores over time.Cognitive 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 score.The 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 score.The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis.The 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.展开更多
Background:The genetic variant of tumor necrosis factor superfamily member 15(TNFSF15)is associated with Crohn’s disease(CD)and the development of intestinal fibrosis and stricturing.We aimed to investigate its predi...Background:The genetic variant of tumor necrosis factor superfamily member 15(TNFSF15)is associated with Crohn’s disease(CD)and the development of intestinal fibrosis and stricturing.We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.Methods:We genotyped the single nucleotide polymorphism rs6478109 within the TNFSF15 gene in 428 CD patients and 450 health controls to assess its association with CD.Genotype-phenotype correlation analyses were performed.Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.Results:The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls(63.3%vs.46.7%,P<0.001).Patients with GG genotype were more predisposed to develop the stricturing phenotype,compared with those with AA?AG genotypes with a hazard ratio of 1.426(95%confidence interval:1.029-1.977,P=0.033).This trend was similarly observed in patients utilizing biological agents,with a hazard ratio of 4.396(95%confidence interval:1.780-10.854,P=0.001).Furthermore,increased TL1A,pro-fibrotic proteins,and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.Conclusions:The TNFSF15 risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.展开更多
Alzheimer＇s disease （AD）, a fatal, progressive, neurodegener- ative disorder, is the most common cause of old-age demen- tia, accounting for 50-75% of dementia patients. Early stages of AD are marked by vocabulary ...Alzheimer＇s disease （AD）, a fatal, progressive, neurodegener- ative disorder, is the most common cause of old-age demen- tia, accounting for 50-75% of dementia patients. Early stages of AD are marked by vocabulary shrinkage, spatial disori- entation, depression, apraxia, and deterioration of recent forms of declarative memory. In course of time, the patients require close supervision due to the loss of cognitive and functional abilities, and at the terminal stages of the disease, all forms of memory are severely impaired with the patients needing nursing home care （World Alzheimer Report, 2013）.展开更多
Huntington’s disease（HD）is an autosomal dominant,monogenic,progressive,neurodegenerative and rare disease with a frequency of10 per 100,000 in the Caucasian population and occurring more rarely in other races（Squi...Huntington’s disease（HD）is an autosomal dominant,monogenic,progressive,neurodegenerative and rare disease with a frequency of10 per 100,000 in the Caucasian population and occurring more rarely in other races（Squitieri et al.,1994）.HD is,nevertheless,one of the most frequently and extensively studied diseases of those caused by a dynamic mutation.The HD mutation is located on the short arm of the 4th chromosome within the HTT gene.展开更多
Background Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein （LDL） cholesterol. However, few studies...Background Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein （LDL） cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.展开更多
基金Supported by the Program of General Hospital of Western Theater,No.2021-XZYG-C33.
文摘Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.
文摘BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and prevention.Although genetic andenvironmental factors have been widely studied,the role of lifestyle factors suchas physical activity,diet,smoking,sleep,and stress remains underexplored,especially in patients with early stage CRC or polyps.Recent evidence suggeststhat lifestyle behaviors may influence cancer progression by modulating inflammatorypathways,metabolic health,and immune function.For instance,highlevels of physical activity are linked to a reduced risk of CRC development,whereas poor dietary habits,smoking,and inadequate sleep have all beenimplicated in increased cancer risk and progression.Moreover,early-stage CRCpatients,who are often asymptomatic or have minimal symptoms,may particularlybenefit from lifestyle modifications to slow disease progression andimprove overall prognosis.The gap in understanding the specific influence ofthese lifestyle factors on colorectal polyps and early stage cancer progressionunderscores the need for comprehensive studies.By assessing several modifiablelifestyle factors and their association with disease progression,clinicians canidentify practical intervention points.These interventions could ultimately reducethe need for more aggressive treatments and improve the long-term outcomes inaffected patients.AIMTo investigate the association between lifestyle factors and disease progression inpatients with colorectal polyps and early stage cancer.METHODSIn this observational study conducted from January 2022 to December 2023,werecruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital.Lifestyle factors,including physical activity,dietary patterns,smoking status,sleep quality,andstress levels,were assessed using validated questionnaires.Disease progression was evaluated using standardizedfollow-up colonoscopies and pathological examinations.Cox proportional hazards models were used to analyzethe association between lifestyle factors and disease progression after adjusting for potential confounders.RESULTSDuring the median follow-up of 18.4 months,42(35.0%)patients experienced disease progression.High levels ofphysical activity were associated with reduced progression risk[adjusted hazard ratio(HR)0.55,95%confidenceinterval(CI):0.38-0.80,P=0.002]compared to low activity levels.High adherence to a healthy dietary patternshowed similar protective effects(adjusted HR 0.62,95%CI:0.43-0.89,P=0.009).Current smoking(adjusted HR1.92,95%CI:1.35-2.73,P<0.001)and poor sleep quality(adjusted HR 1.38,95%CI:1.05-1.82,P=0.021)wereassociated with increased progression risk.The impact of lifestyle factors was particularly pronounced in patientsyounger than 60 years and those with multiple polyps at baseline.CONCLUSIONThis study demonstrated significant associations between lifestyle factors and disease progression in colorectalpolyps and early stage cancer.Physical activity,dietary patterns,smoking status,and sleep quality have emergedas key modifiable factors influencing disease progression.These findings support the integration of lifestyleassessments and modifications in the clinical management of patients with colorectal neoplasia.
文摘This study aims to understand the current status of fear of disease progression(FoP)in patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI),and to explore the relationship between FoP levels,perceived control,and medical coping strategies in these patients.A total of 360 CHD patients who underwent PCI at Xijing Hospital in Shaanxi Province between June and November 2024 were selected using a convenience sampling method.Surveys included a general information questionnaire,the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the revised Control Attitudes Scale(CAS-R),and the Medical Coping Modes Questionnaire(MCMQ).Pearson correlation analysis was used to examine the relationships between disease perception,positive coping strategies,and FoP.A total of 360 patients completed the study.The average score for FoP in patients with CHD after PCI was 31.64±4.61.FoP was negatively correlated with perceived control(r=-0.106,P<0.01)and medical coping(r=-0.194,P<0.01).Multivariate regression analysis showed that the type of intervention,family history of CHD,smoking status,perceived control,and total medical coping score were significant factors influencing FoP(P<0.01).Enhancing perceived control and identifying positive coping strategies can improve FoP levels in patients with CHD after PCI.Therefore,clinicians should focus on perceived control and medical coping levels in patients and develop targeted interventions to alleviate negative emotions related to FoP.
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With 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 base.The 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 outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The 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.
文摘BACKGROUND The mental well-being of individuals with coronary heart disease(CHD)during the intensive care unit(ICU)transition period is a multifaceted and significant concern.In this phase,the individuals might encounter psychological challenges like anxiety and depression,which can impede their recuperation and potentially have lasting effects on their health.AIM To investigate the correlation among psychological factors in CHD patients in the ICU transition period.METHODS A questionnaire survey was conducted with 119 patients admitted to the ICU after coronary artery bypass grafting between March and December 2023.Variations in Hamilton Anxiety Scale(HAMA)and Hamilton Depression Scale(HAMD),Fear of Progression Questionnaire-Short Form(Fop-Q-SF),and Social Support Rating Scale(SSRS)were collected and analyzed among diverse populations.We used Pearson’s correlation analysis to examine the correlation.Multiple linear regression analysis was used to explore whether these indicators influenced depression and anxiety in the patients.RESULTS The total scores for anxiety,depression,fear of disease progression,and social support were(7.50±1.41)points,(8.38±1.62)points,(35.19±8.14)points,and(36.34±7.08)points,respectively(P<0.05).Multivariate regression analysis showed that both the level of disease progression and social support affected the level of postoperative depression and anxiety in patients.CONCLUSION The anxiety and depression levels were positively related to each dimension of phobia disease progression and negatively related to each dimension of social support among patients with CHD.
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based 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 onset.Since 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 regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal 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 phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The 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 metabolites.This 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 disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
基金supported by a grant from National Institute of Health(NIH)Grant No.NS040433
文摘Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates：a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.
文摘Multiple Sclerosis（MS） is a major cause of neurological disability in adults and has an annual cost of approximately $28 billion in the United States. MS is a very complex disorder as demyelination can happen in a variety of locations throughout the brain; therefore, this disease is never the same in two patients making it very hard to predict disease progression. A modeling approach which combines clinical, biological and imaging measures to help treat and fight this disorder is needed. In this paper, I will outline MS as a very heterogeneous disorder, review some potential solutions from the literature, demonstrate the need for a biomarker and will discuss how computational modeling combined with biological, clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism.
基金supported by grant KOMFI 13-04-40106-H (Russia):"Structure-functional studies of р-75 receptor–molecular target for neurodegenerative diseases immunotherapy"Grant RFBR 13-04-00633A (Russia):"Study of role of receptor for advanced glycation end products (RAGE) in mechanisms of beta-amyloid neurotoxicity in model of sporadic Alzheimer’s disease"
文摘Compensatory/adaptive mechanisms in the brain are hy- pothesized to be involved in its protection from the Alz- heimer＇s disease （AD） progression. These mechanisms are activated by malfunctioning of various brain systems： anti- oxidant, neurotrophic, neurotransmitter, immune, and oth- ers. Detailed analysis of compensatory^adaptive capabilities of these systems might be a start point for further discovery and development of perspective approaches for early diag- nostics and treatment of AD and associated neurodegenera- tive disorders.
文摘BACKGROUND Transarterial chemoembolization(TACE)is widely performed for intermediatestage or unresectable hepatocellular carcinoma(HCC),but approximately half of patients do not respond to TACE treatment.We describe a case of rapidly progressing of HCC after TACE and provide a possible hypothesis for this condition.The 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 window.CASE 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 ago.The tumor recurred in the two months after surgery.She 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 TACE.However,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 image.One month later,she had a third TACE to control the residual HCC tumors.Two weeks after that,the HCC had increased dramatically with tea-colored urine and yellowish skin turgor.Eventually,the patient refused further treatment and went into hospice care.CONCLUSION Intense hypoxia induced by TACE can trigger rapid disease progression in infiltrative HCC patients with a large tumor burden.
基金supported by the National Key Technology R&D Program of China(No.2020YFC0840800).
文摘Objective:The COVID-19 pandemic poses a significant threat to global health.Given 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 patients.Methods: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 information.Disease progression was defined as progressing to severe critical illness after admission.The LASSO regression was used to select the predicted variables and a logistic regression model was applied to build the predictive model.Nomogram was used to show the results.Results: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.
文摘Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer of a cancer hospital in Tianjin were selected as the research objects by the convenience sampling method.The general data questionnaire,spouse fear of disease progression scale and self-efficacy scale were used to investigate.Multiple linear regression was used to analyze the influencing factors of the fear of the disease progression in the postoperative pa tients’spouse of bladder cancer.Results:The score of fear of disease progression was(35.75±9.86).The results of multiple linear regression analysis showed that the spouse’s age,medical payment method,occupational status and self-efficacy were the main influencing factors for the spouse’s fear of disease progression after bladder cancer(P<0.05),which accounted for 55%of the total variation.Conclusion:The spouse’s fear of disease progression in patients with bladder cancer is at a moderate lev el,and age,medical payment method,occupational status and self-efficacy are the main influencing factors.It is suggested that clinical medical staff focus on young,rural cooperative medical care,self-financed,in-service,and unemployed,low self-eff icacy of postoperative bladder cancer patients'spouses.A series of psychological counseling and health education should be given to help the patient spouse correctly understand and deal with diseases,reduce the patients’spouses of negative emotions,im prove the patients’spouses of self-efficacy,and reduce the spouse fear level of disease progression.
文摘Objective To use high-throughput transcriptome sequencing data to screen for a set of non-invasive diagnostic biomarkers for assessing the risk of pulmonary tuberculosis(PTB)and predicting disease progression stages.Methods A total of 37 effective microarray transcriptome datasets were collected from the National Center for Biotechnology Information(NCBI)from January 2015 to December 2024,covering five groups:control group,PTB group,extrapulmonary TB(EPTB)group,latent TB infection(LTBI)group,and other diseases(OD)group.
文摘Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas.The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated.In this observational study,we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases(LBDs)and Alzheimer disease(AD),shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration.We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival.Disease progression in LBDs correlated positively with poly(ADP-Ribose)and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts,indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes.Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxo-d G)and myeloperoxidase concentrations in the striatum,suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism ofβ-amyloid entering the mitochondria and subsequent free radicals generation.Patients with lower striatal 8-oxo-d G and myeloperoxidase levels had a survival advantage in AD.The age of onset also affected disease progression.Tissue requests for the postmortem biochemistry,genetics,and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center(ADRC)Biospecimens Committee(ethics approval reference number:T1705,approval date:August 6,2019).Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health&Safety Biological Safety Committee(approval code:3739,approval date:February 25,2020).Radioactive Material Authorization was approved by the Washington University Environmental Health&Safety Radiation Safety Committee(approval code:1056,approval date:September 18,2019).
基金Open Access funding enabled and organized by Projekt DEAL。
文摘Background:Interventional trials in amyotrophic lateral sclerosis(ALS)sufer from the heterogeneity of the disease as it considerably reduces statistical power.We asked if blood neuroflament light chains(NfL)could be used to antici‑pate disease progression and increase trial power.Methods: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)score.We 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 onset.We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials.We 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 approaches.The 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 power.NCT00868166,registered March23,2009;NCT02306590,registered December 2,2014.
基金from McGee Fellowship fund and a University of Otago Doctoral Scholarship.The authors are grateful to the HD patients,healthy controls and Ms.Maggie Jury,coordinator of clinical services for HD patients in Christchurch,for their participation and support in this project.
文摘Progressive cognitive decline is a feature of Huntington’s disease(HD),an inherited neurodegenerative movement disorder.Comprehensive neuropsychological testing is the‘gold standard’to establish cognitive status but is often impractical in time-constrained clinics.The 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 HD.Twenty-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 group.The controls exhibited a practice effect in most of the cognitive domain scores over time.Cognitive 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 score.The 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 score.The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis.The 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.
基金supported by the Sun Yat-sen University Clinical Research 5010 Program[grant number 2014008]the National Natural Science Foundation of China[grant number 82270544]+2 种基金the Sixth Affiliated Hospital“Jie Bang Gua Shuai”Program[grant number 2022JBGS06]the Science and Technology Program of Guangzhou,China[grant number SL2022B03J00237]the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases[grant number 2020B1111170004].
文摘Background:The genetic variant of tumor necrosis factor superfamily member 15(TNFSF15)is associated with Crohn’s disease(CD)and the development of intestinal fibrosis and stricturing.We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.Methods:We genotyped the single nucleotide polymorphism rs6478109 within the TNFSF15 gene in 428 CD patients and 450 health controls to assess its association with CD.Genotype-phenotype correlation analyses were performed.Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.Results:The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls(63.3%vs.46.7%,P<0.001).Patients with GG genotype were more predisposed to develop the stricturing phenotype,compared with those with AA?AG genotypes with a hazard ratio of 1.426(95%confidence interval:1.029-1.977,P=0.033).This trend was similarly observed in patients utilizing biological agents,with a hazard ratio of 4.396(95%confidence interval:1.780-10.854,P=0.001).Furthermore,increased TL1A,pro-fibrotic proteins,and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.Conclusions:The TNFSF15 risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.
基金in part supported by the German Ministry for Education and Research (BMBF) special network program KMU-Innovativ-2
文摘Alzheimer＇s disease （AD）, a fatal, progressive, neurodegener- ative disorder, is the most common cause of old-age demen- tia, accounting for 50-75% of dementia patients. Early stages of AD are marked by vocabulary shrinkage, spatial disori- entation, depression, apraxia, and deterioration of recent forms of declarative memory. In course of time, the patients require close supervision due to the loss of cognitive and functional abilities, and at the terminal stages of the disease, all forms of memory are severely impaired with the patients needing nursing home care （World Alzheimer Report, 2013）.
文摘Huntington’s disease（HD）is an autosomal dominant,monogenic,progressive,neurodegenerative and rare disease with a frequency of10 per 100,000 in the Caucasian population and occurring more rarely in other races（Squitieri et al.,1994）.HD is,nevertheless,one of the most frequently and extensively studied diseases of those caused by a dynamic mutation.The HD mutation is located on the short arm of the 4th chromosome within the HTT gene.
文摘Background Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein （LDL） cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.
