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SARS-CoV-2 productively infects primary human immune system cells in vitro and in CoviD-19 patients

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Journal of Molecular Cell Biology 2022年第4期14卷 51-64页

作者： Marjorie C.Pontelli italo A.Castro Ronaldo B.Martins Leonardo La Serra Flavio P.Veras Daniele C.Nascimento Camila M.Silva Ricardo S.Cardoso Roberta Rosales Rogério Gomes Thais M.Lima Juliano P.Souza Brenda C.Vitti Diego B.Caetite Mikhael H.F.de Lima Spencer D.Stumpf Cassandra E.Thompson Louis-Marie Bloyet Juliana E Toller-Kawahisa Marcela C.Giannini Leticia P.Bonjorno Marial.F.Lopes Sabrina S.Batah Li Siyuan Rodrigo Luppino-Assad Sergio C.L.Almeida Fabiola R.Oliveira Maira N.Benatti Lorena L.F.Pontes Rodrigo C.Santana Fernando C.Vilar Maria Auxiliadora-Martins Pei-Yong Shi Thiago M.Cunha Rodrigo T.Calado JoséC.Alves-Filho Dario S.Zamboni Alexandre T.Fabro Paulo Louzada-Junior Rene D.R.Oliveira Sean P.J.Whelan Fernando Q.Cunha Eurico Arruda Virology Research Center Ribeirao Preto Medical SchoolUniversity of Sao Pauloibeirao PretoSao Paulo 14049-900.Brazil Center of Research in Inflammatory Diseases Ribeirao Preto Medical SchoolUniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of Celland Molecular Biology Ribeirao Preto Medical SchoolUniversityof Sao PauloRibeirao PretoSao Paulo 14049-900 Brazil Regional Blood Centerof Ribeirao Preto Ribeirao Preto Medical ScholUniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of Biochemistry&Molecular Biology the University of Texas Medical BranchGalvestonTX7755USA Divisions of Clinical lmmunology Infectious Diseases and Intensive Care UnitRibeirao Preto Medical Schooniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of Pathology Ribeirao Preto Medical Scholniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of Molecular Microbiology.Washington University in St.Louis Saint LouisMO 63110USA

The severe acute respiratory syndrome coronavirus 2(SARS-CovV-2)infection is associated with a hyperinflammatory state and Lymphocytopenia,a hallmark that appears as both signature and prognosis of disease severity outcome.Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion,it is still unclear whether direct SARS-Cov-2 infection of immune cells could also play a role in this scenario by harboring viral replication.We found that monocytes,as well as both B and T lymphocytes,were susceptible to SARS-Cov-2 infection in vitro,accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis.In addition,flow cytometry and immunofluorescence analysis revealed that SARS-Cov-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019(CoVID-19)patients.The rates of SARS-Cov-2-infected monocytes in peripheral blood mononuclear cells from CoVID-19 patients increased over time from symptom onset,with SARS-CoV-2-positive monocytes,B cells,and CD4+T lymphocytes also detected in postmortem lung tissue.These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in covID-19 patients might have important implications for disease pathogenesis and progression,immune dysfunction,and virus spread within the host.

关键词： SARS-CoV-2 CoVID-19 Lymphocytopenia peripheral blood mononuclear cell(PBMC) lymphocytes monocytes apoptosis

Prevalence and risk factors of lymphatic dysfunction in cirrhosis patients with refractory ascites:An often unconsidered mechanism

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World Journal of Hepatology 2023年第10期15卷 1140-1152页

作者： Rahul Arya Ramesh Kumar Tarun Kumar Sudhir Kumar Utpal Anand Rajeev Nayan Priyadarshi Tanmoy Maji Department of Gastroenterology All India Institute of Medical SciencesPatna 801507BiharIndia Department of Pathology All India Institute of Medical SciencesPatna 801507BiharIndia Department of Surgical Gastroenterology All India Institute of Medical SciencesPatna 801507BiharIndia Department of Radiodiagnosis All India Institute of Medical SciencesPatna 801507BiharIndia

BACKGROUND The lymphatic system is crucial in maintaining the body fluid homeostasis.A dysfunctional lymphatic system may contribute to the refractoriness of ascites and edema in cirrhosis patients.Therefore,assessment of lymphatic dysfunction in cirrhosis patients with refractory ascites(RA)can be crucial as it would call for using different strategies for fluid mobilization.AIM To assessing the magnitude,spectrum,and clinical associations of lymphatic dysfunction in liver cirrhosis patients with RA.METHODS This observational study included 155 consecutive cirrhosis patients with RA.The presence of clinical signs of lymphedema,such as peau d’orange appearance and positive Stemmer sign,intestinal lymphangiectasia(IL)on duodenal biopsy seen as dilated vessels in the lamina propria with strong D2-40 immunohistochemistry,and chylous ascites were used to diagnose the overt lymphatic dysfunctions.RESULTS A total of 69(44.5%)patients out of 155 had evidence of lymphatic dysfunction.Peripheral lymphedema,found in 52(33.5%)patients,was the most common manifestation,followed by IL in 42(27.0%)patients,and chylous ascites in 2(1.9%)patients.Compared to patients without lymphedema,those with lymphedema had higher mean age,median model for end-stage liver disease scores,mean body mass index,mean ascitic fluid triglyceride levels,and proportion of patients with hypoproteinemia(serum total proteinLymphocytopenia(Lymphocytopenia and hypoproteinemia(28.6%vs.9.1%,P=0.004).Seven(13%)patients with lymphedema had lower limb cellulitis compared to none in those without it.On multivariate regression analysis,factors independently associated with lymphatic dysfunction included obesity[odds ratio(OR):4.2,95%confidence intervals(95%CI):1.1–15.2,P=0.027],Lymphocytopenia[OR:6.2,95%CI:2.9–13.2,P<0.001],and hypoproteinemia[OR:3.7,95%CI:1.5–8.82,P=0.003].CONCLUSION Lymphatic dysfunction is common in cirrhosis patients with RA.Significant indicators of i

关键词： Cirrhosis Lymphedema Lymphangicetasia Refractory ascites Chylous ascites Lymphocytopenia

Seronegative autoimmune hepatitis in childhood

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World Journal of Clinical Pediatrics 2023年第3期12卷 77-85页

作者： Ali Islek Gokhan Tumgor Department of Pediatric Gastroenterology Cukurova University School of Medicine

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children,although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis.Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated.The absence of autoantibody positivity,hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease.In general,seronegative autoimmune hepatitis often presents with acute hepatitis,and its treatment and prognosis similar to seropositive autoimmune hepatitis.The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood,and those of which current knowledge is vague.

关键词： Seronegative autoimmune hepatitis Autoantibody negative Lymphocytopenia Aplastic anemia

Lymphocytopenia and Neutrophilia Deteriorate at the Lowest Oxygenation Index Timepoint in COVID-19 Patient

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International Journal of Clinical Medicine 2020年第12期11卷 810-822页

作者： Yiwen Xu Weijun Hong Gang Wu Weiling Li Chunqiang Xu Xiaofei Hu Meixian Zhang Huihui Xu En Wang Shaofa Ke Xiaoping Jin Department of Neurology Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China The First Clinical Medical College Wenzhou Medical University Wenzhou China Department of Pharmacy Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China Public Experiment Center Medical Research Center Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China Laboratory of Gynecologic Oncology Medical Research Center Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University Linhai China

Objective: Coronavirus disease 2019 (COVID-19) spread throughout the world and caused hundreds of thousands of infected people to death. However, the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) is poorly understood. The objective of this study is to retrospectively explore the pathogenesis of COVID-19 from clinical laboratory findings, taking disease progression into account. Methods: A single-centered, retrospective study was carried out, which included moderate (n = 76) and severe COVID-19 cases (n = 22). The difference of laboratory findings from blood routine examination and hepatorenal function test were retrospectively evaluated between the state of moderate and severe. The disease progression was indicated by oxygenation index. Results: Age is a risk factor for disease progression from moderate to severe. Lymphocytopenia, neutrophilia, liver and kidney function decreasement occurred in severe patients on admission, compared with moderate patients. Lymphocytopenia and neutrophilia deteriorated at the lowest oxygenation index timepoint in the severe patients. And the oxygenation index was associated with ratio of lymphocyte and neutrophil in COVID-19 patients. Conclusions: Lymphocytopenia and neutrophilia, which deteriorate in the progression of severe patients, are the main pathogenesis of COVID-19. More measures need to be taken to control Lymphocytopenia and neutrophilia in severe COVID-19. Oxygenation index presented potentiality as predictor on the progression of COVID-19.

关键词： COVID-19 Oxygenation Index Lymphocytopenia Neutrophilia Glucocorticoids

Primary intestinal lymphangiectasia with generalized warts

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World Journal of Gastroenterology 2015年第27期21卷 8467-8472页

作者： Soon Jae Lee Hyun Joo Song Sun-Jin Boo Soo-Young Na Heung Up Kim Chang Lim Hyun Department of Internal Medicine Jeju National University School of Medicine Department of Pathology Jeju National University School of Medicine

Primary intestinal lymphangiectasia(PIL) is a rare protein-losing enteropathy with lymphatic leakage into the small intestine. Dilated lymphatics in the small intestinal wall and mesentery are observed in this disease. Laboratory tests of PIL patients revealed hypoalbuminemia, Lymphocytopenia, hypogammaglobulinemia and increased stool α-1 antitrypsin clearance. Cell-mediated immunodeficiency is also present in PIL patients because of loss of lymphocytes. As a result, the patients are vulnerable to chronic viral infection and lymphoma. However, cases of PIL with chronic viral infection, such as human papilloma virus-induced warts, are rarely reported. We report a rare case of PIL with generalized warts in a 36-year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic biopsy with histological tissue confirmation. Generalized warts were observed on the head, chest, abdomen, back, anus, and upper and lower extremities, including the hands and feet of the patient.

关键词： Protein-losing enteropathy Lymphocytopenia Cell-mediated immunodeficiency Primary intestinallymphangiectasia Warts

Novel Approach to Chemotherapy and Administration Selection with Metronomic/Fractionated Dosing

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Journal of Cancer Therapy 2015年第5期6卷 455-465页

作者： Aaron J. Smith John Oertle Dino Prato Envita Scottsdale AZ USA

Metronomic dosing of chemotherapy was introduced in the early 2000s and has since gained recognition as a potential game changer in the manner of which chemotherapy can be administered. There are several known candidates for metronomic dosing of chemotherapy with the potential for many more to be elucidated in the future. Minimized overall side effects, longer durations of treatment, potential minimization of multidrug resistance (MDR) mutations, potential less refractory responses, and the potential to safely use more than one chemotherapy treatments also make metronomic dosing of chemotherapy attractive. Metronomic dosing reduces common side effects and has the potential to reduce neutropenia, Lymphocytopenia, and cognitive changes associated with maximum tolerated dosages (MTD). Methods of enhancing chemotherapy including fasting and administration of insulin are also discussed. Metronomic dosing combined with a patient’s molecular profile derived from biomarkers is particularly exciting. It holds significant potential with regard to administrating the most relevant chemotherapies and offers maximal beneficial results.

关键词： Metronomic Dosing Chemotherapy Multidrug Resistance Neutropenia Lymphocytopenia Insulin Biomarkers Cognitive Changes

Experimental Haematobiochemical Alterations in Broiler Chickens Fed with T-2 Toxin and Co-Infected with IBV

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Open Journal of Veterinary Medicine 2013年第5期3卷 252-258页

作者： T. Yohannes A. K. Sharma S. D. Singh V. Sumi College of Veterinary Science Mekelle University Mekelle Ethiopia

The purpose of this experimental study was to evaluate and record the effects of T-2 toxicity alone and in association with IBV infection on haematobiochemical parameters. A total of 128 one-week-old chicks were divided into four groups of 32 birds each and were treated respectively with T-2 toxin alone, IBV alone, T-2 toxin and co-infected with IBV, and no treatment (control) for a period of 6 weeks. Haematologically, the birds treated with T-2 toxin developed anaemia as indicated by significant decrease in haemoglobin levels, total erythrocyte counts and packed cell volume values;leucopenia, Lymphocytopenia heterophilia and thrombocytopenia. The IBV infected birds exhibited lymphocytophilia and heteropoenia;the degrees of severity of leucopenia, Lymphocytopenia heterophilia and thrombocytopenia were more pronounced in T-2+IBV groups. The serum biochemistry revealed hypoproteinemia and hypoalbuminemia in all the treated groups consistently. Besides, hypoglobulinemia and increased levels of alanine aminotransferase in T-2+IBV, and increased levels of alkaline phosphatase in toxin group alone were recorded. The changes in biochemical parameters were more in magnitude in the combination treatment group and their severity increased with duration of treatment. It was concluded that T-2 toxin made the birds more susceptible to IBV infection.

关键词： Anaemia Hypoproteinenemia IBV Lymphocytopenia T-2 Toxin Thrombocytopenia