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Persistently Rising Alpha-fetoprotein in the Diagnosis of Hepatocellular Carcinoma:A Review

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Journal of Clinical and Translational Hepatology 2022年第1期10卷 159-163页

作者： Alla Turshudzhyan George Y.Wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Hepatocellular carcinoma(HCC),one of the most common malignant tumors worldwide,is known for its grim prognosis,with untreated life expectancy being only a matter of months after the *** difficulty in making a diagnosis early is one of the main contributing factors to the poor ***-fetoprotein(AFP)had long been used as a surveillance tool,but suboptimal specificity and sensitivity has prompted liver societies to abandon the recommendation for its universal use,even in combination with *** studies have shown no obvious correlation between serum AFP level and HCC tumor size,stage,or survival ***,some studies concluded that a gradual rise or persistent elevation in AFP were positive predictors for tumor *** studies reported a fall in AFP followed by a rise in patients with HCC as well as persistently rising AFP levels without development of HCC on follow *** calculation of the sensitivity and specificity of persistently rising AFP for HCC were both low,at 60%and 35.8%,respectively,indicating that the presence of persistently rising AFP per se did not offer diagnostic *** addition,our calculated mean slopes of persistently rising AFP levels in HCC and non-HCC patients were numerically very different,but the difference was not statistically *** conclude that the published data do not support a role for rising AFP levels per se in the diagnosis of HCC.

关键词： Alpha-fetoprotein,AFP Hepatocellular carcinoma,HCC Cancer screening

Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases:A clinical review

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World Journal of Gastrointestinal Oncology 2016年第5期8卷 459-465页

作者： Irene Sarosiek Rudolf Schicho Pedro Blandon Mohammad Bashashati division of Gastroen-terology Department of Internal MedicineTexas Tech University Health Sciences Center Institute of Experimental and Clinical Pharma-cology Medical University of Graz division of Nephrology Department of Internal MedicineTexas Tech University Health Sciences Center

The diagnosis of gastrointestinal(GI) disorders is usually based on invasive techniques such as endoscopy.A key important factor in GI cancer is early diagnosis which warrants development of non-or lessinvasive diagnostic *** addition,monitoring and surveillance are other important parts in the management of GI *** studies with nuclear magnetic resonance and mass spectrometry can measure the concentration of more than 3000 chemical compounds in the urine providing possible chemical signature in different diseases and during *** this review,we discuss the urinary metabolomics signature of different GI diseases including GI cancer and elaborate on how these biomarkers could be used for the classification,early diagnosis and the monitoring of the ***,we discuss future directions of this still evolving field of research.

关键词： Metabolomics Gastrointestinal diseases Cancer Inflammatory bowel disease Metabolome Urine

Qidong: a crucible for studies on liver cancer etiology and prevention

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Cancer Biology & Medicine 2019年第1期16卷 24-37页

作者： Jianguo Chen Jian Zhu Gaoren Wang John D.Groopman Thomas W.Kensler Department of Epidemiology Qidong Liver Cancer Institute Department of Epidemiology Tumor Hospital Nantong University Department of Environmental health and Engineering Johns Hopkins Bloomberg School of Public Health Public health Sciences division Fred Hutchinson Cancer Research Center

Qidong(Jiangsu, China) has been of interest to cancer epidemiologists and biologists because, until recently, it was an endemic area for liver cancer, having amongst the highest incidence rates in the world. The establishment of the Qidong Cancer Registry together with the Qidong Liver Cancer Institute in 1972 has charted the patterns of liver cancer incidence and mortality in a stable population throughout a period of enormous economic, social, and environmental changes as well as of improvements in health care delivery. Updated incidence trends in Qidong are described. Notably, the China age-standardized incidence rate for liver cancer has dropped by over 50% in the past several decades. Molecular epidemiologic and genomic deep sequencing studies have affirmed that infection with hepatitis B virus as well as dietary exposure to aflatoxins through contamination of dietary staples such as corn, and to microcystins–blue-green algal toxins found in ditch and pond water – were likely important etiologic factors that account for the high incidence of liver cancer in this region. Public health initiatives to facilitate universal vaccination of newborns against HBV and to improve drinking water sources in this rural area, as well as economic and social mandates serendipitously facilitating dietary diversity, have led to precipitous declines in exposures to these etiologic factors, concomitantly driving substantive declines in the liver cancer incidence seen now in Qidong. In this regard, Qidong serves as a template for the global impact that a package of intervention strategies may exert on cancer burden.

关键词： Liver cancer incidence hepatitis B virus aflatoxin microcystin screening chemoprevention mutational signature

Factors associated with mobile phone ownership and potential use for rabies vaccination campaigns in southern Malawi

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Infectious Diseases of Poverty 2020年第3期9卷 136-137页

作者： Orla Marron Gareth Thomas Jordana LBurdon Bailey Dagmar Mayer Paul OGrossman Frederic Lohr Andy DGibson Luke Gamble Patrick Chikungwa Julius Chulu Ian GHandel Barend Mde C Bronsvoort Richard JMellanby Stella Mazeri 不详 The Royal(Dick)School of Veterinary studies Division of Veterinary Clinical StudiesThe University of EdinburghHospital for Small AnimalsEaster Bush Veterinary CentreRoslinMidlothianUK

Background:Rabies is a fatal but preventable viral disease,which causes an estimated 59000 human deaths globally every *** vast majority of human rabies cases are attributable to bites from infected domestic dogs and consequently control of rabies in the dog population through mass vaccination campaigns is considered the most effective method of eliminating the *** the WHO target of 70%vaccination coverage has proven challenging in low-resource settings such as Sub Saharan Africa,and lack of public awareness about rabies vaccination campaigns is a major barrier to their *** this study we surveyed communities in three districts in Southern Malawi to assess the extent of and socio-economic factors associated with mobile phone ownership and explore the attitudes of communities towards the use of short message service(SMS)to inform them of upcoming rabies vaccination ***:This study was carried out between 1 October–3 December 2018 during the post-vaccination assessment of the annual dog rabies campaign in Blantyre,Zomba and Chiradzulu districts,Malawi.1882 questionnaires were administered to households in 90 vaccination *** surveys gathered data on mobile phone ownership and use,and barriers to mobile phone access.A multivariable regression model was used to understand factors related to mobile phone ***:Most survey respondents owned or had use of a mobile phone,however there was evidence of an inequality of access,with higher education level,living in Blantyre district and being male positively associated with mobile phone *** principal barrier to mobile phone ownership was the cost of the phone *** feature phones were most common and few owned *** was commonly used and the main reason for not using SMS was *** to receiving SMS reminders about future rabies vaccination campaigns were ***:The study showed a majority of those surveyed have the use of

关键词： Rabies Mass vaccination mhealth Short message service

Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis

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World Journal of Gastroenterology 2017年第15期23卷 2673-2684页

作者： Agata Bartczak Jianhua Zhang Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski Nazia Selzner Andrzej Chruscinski Gary A Levy Multi Organ Transplant Program University Health Network Department of Laboratory Medicine and Pathology University Health Network Gastroenterology Hepatology and Nutrition DivisionThe Hospital for Sick Children

AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1-/- *** and Teff cells from fgl2-/-, fgl2+/+, and fgl2Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/- *** vitro, fgl2Tg Treg had enhanced immunosuppressive activity, and fgl2Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2+/+) into Rag1-/- mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/- Treg were only partially protective. In mice that received fgl2Tg Treg, the ratio of Foxp3+ to CD3+ cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2Tg mice did not produce *** we show that fgl2Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2Tg Treg prevent colitis in contrast to fgl2+/+ Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.

关键词： Fibrinogen-like protein 2 Colitis Regulatory T cells Transgenic mouse Inflammatory bowel disease

Cytomegalovirus Hepatitis in Immunocompetent and Immunocompromised Hosts

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 106-115页

作者： Teresa Da Cunha George Y.Wu Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA

Human cytomegalovirus (HCMV) infection is common and affects between 40–100% of the worldwide population. However, the majority of cases are asymptomatic and when severe disease occurs, it is usually restricted to immunocompromised patients. Liver involvement by HCMV differs significantly, accordingly to the immune status of the host. In immunocompromised patients, particularly liver transplant patients, it often causes clinically significant hepatitis. On the other hand, in immunocompetent patients, HCMV hepatitis requiring hospitalization is extremely rare. This review aims to appraise studies regarding the pathophysiology of HCMV hepatitis, including mechanisms of latency and reactivation and its contribution to disease development, clinical presentation, diagnostic modalities and treatment, with a focus on comparing different aspects between immunocompromised and immunocompetent hosts.

关键词： CMV hepatitis Cytomegalovirus hepatitis Cytomegalovirus hepatitis immunocompetent Cytomegalovirus hepatitis immunocompromised

Non-conventional modeling of extreme significant wave height through random sets

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Acta Oceanologica Sinica 2014年第7期33卷 125-130页

作者： ZHANG Yi LAM Jasmine Siu Lee division of Infrastructure Systems and Maritime studies School of Civil and Environmental EngineeringN1-B1a-25 Nanyang Technological UniversitySingapore division of Infrastructure Systems and Maritime studies School of Civil and Environmental EngineeringN1-01b-43 Nanyang Technological UniversitySingapore

The analysis and design of offshore structures necessitates the consideration of wave loads. Realistic modeling of wave loads is particularly important to ensure reliable performance of these structures. Among the available methods for the modeling of the extreme significant wave height on a statistical basis, the peak over threshold method has attracted most attention. This method employs Poisson process to character- ize time-varying properties in the parameters of an extreme value distribution. In this paper, the peak over threshold method is reviewed and extended to account for subjectivity in the modeling. The freedom in selecting the threshold and the time span to separate extremes from the original time series data is incorpo- rated as imprecision in the model. This leads to an extension from random variables to random sets in the probabilistic model for the extreme significant wave height. The extended model is also applied to different periods of the sampled data to evaluate the significance of the climatic conditions on the uncertainties of the parameters.

关键词： offshore engineering extreme value distribution wave height peak over threshold randomset Pareto distribution

A fuzzy quantification approach of uncertainties in an extreme wave height modeling

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Acta Oceanologica Sinica 2015年第3期34卷 90-98页

作者： ZHANG Yi CAO Yingyi division of Infrastructure Systems and Maritime studies School of Civil and Environmental EngineeringNanyang Technological University College of Preschool Education Zibo Normal College

A non-traditional fuzzy quantification method is presented in the modeling of an extreme significant wave height. First, a set of parametric models are selected to fit time series data for the significant wave height and the extrapolation for extremes are obtained based on high quantile estimations. The quality of these results is compared and discussed. Then, the proposed fuzzy model, which combines Poisson process and gener-alized Pareto distribution （GPD） model, is applied to characterizing the wave extremes in the time series data. The estimations for a long-term return value are considered as time-varying as a threshold is regarded as non-stationary. The estimated intervals coupled with the fuzzy theory are then introduced to construct the probability bounds for the return values. This nontraditional model is analyzed in comparison with the traditional model in the degree of conservatism for the long-term estimate. The impact on the fuzzy bounds of extreme estimations from the non stationary effect in the proposed model is also investigated.

关键词： offshore engineering extreme value distribution wave height peak over threshold fuzzy set Pareto distribution

Neuromodulation and ablation with focused ultrasound-toward the future of noninvasive brain therapy

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Neural Regeneration Research 2019年第9期14卷 1509-1510页

作者： Anton Fomenko Andres M.Lozano Krembil Research Institute University Health NetworkTorontoCanada division of Neurosurgery Toronto Western HospitalTorontoCanada

With an aging patient population and an increased burden of neurological disease,the demand for noninvasive alternatives to open neurosurgical procedures is *** or minimally invasive approaches to targeting brain regions include transcranial magnetic stimulation(TMS),transcranial direct current stimulation,temporally interfering electric fields,and focused ultrasound(FUS).Among these modalities,FUS offers a unique combination of target specificity,deep brain penetration,and compatibility with real-time structural and thermal monitoring using magnetic resonance imaging(MRI)and MR *** on the intensity and frequency used,ultrasound can have either modulating or ablative effects on brain ***-intensity MR-guided FUS(MRgFUS)is a noninvasive and effective alternative to conventional deep-brain stimulation and radiofrequency lesioning for essential tremor(ET),and is being investigated for other movement disorders,particularly Parkinson’s *** clinical implementation of high-intensity ultrasound is challenged by limitations in target selection precision,technical barriers(such as variable penetration and heat deposition)and the possibility of lesion-related adverse effects(Schwartz et al.,2018).Emerging studies,including those from our group(Boutet et al.,2018)are striving to refine targeting of MRgFUS to improve safety and patient clinical *** the same time,low-intensity FUS(LIFUS)has been found to safely modulate brain activity in rodents,primates,and healthy human subjects(Fomenko et al.,2018).Clinical translation of LIFUS has been hampered however,by a poor understanding of the mechanisms of action,uncertainty over effective sonication parameters and intensities,and conflicting study results due to heterogeneous experimental *** this perspective,the current state of both MRgFUS ablation and LIFUS neuromodulation will be *** technical challenges to delivering ultrasound to the brain,recen

关键词： precision procedures Parkinson human same FUS can has