269 research outputs found

    Attribute Equilibrium Dominance Reduction Accelerator (DCCAEDR) Based on Distributed Coevolutionary Cloud and Its Application in Medical Records

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    © 2013 IEEE. Aimed at the tremendous challenge of attribute reduction for big data mining and knowledge discovery, we propose a new attribute equilibrium dominance reduction accelerator (DCCAEDR) based on the distributed coevolutionary cloud model. First, the framework of N-populations distributed coevolutionary MapReduce model is designed to divide the entire population into N subpopulations, sharing the reward of different subpopulations' solutions under a MapReduce cloud mechanism. Because the adaptive balancing between exploration and exploitation can be achieved in a better way, the reduction performance is guaranteed to be the same as those using the whole independent data set. Second, a novel Nash equilibrium dominance strategy of elitists under the N bounded rationality regions is adopted to assist the subpopulations necessary to attain the stable status of Nash equilibrium dominance. This further enhances the accelerator's robustness against complex noise on big data. Third, the approximation parallelism mechanism based on MapReduce is constructed to implement rule reduction by accelerating the computation of attribute equivalence classes. Consequently, the entire attribute reduction set with the equilibrium dominance solution can be achieved. Extensive simulation results have been used to illustrate the effectiveness and robustness of the proposed DCCAEDR accelerator for attribute reduction on big data. Furthermore, the DCCAEDR is applied to solve attribute reduction for traditional Chinese medical records and to segment cortical surfaces of the neonatal brain 3-D-MRI records, and the DCCAEDR shows the superior competitive results, when compared with the representative algorithms

    Corticosteroid plus glycyrrhizin therapy for chronic drug‐ or herb‐induced liver injury achieves biochemical and histological improvements: a randomised open‐label trial

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    BackgroundTreatment of chronic drug-induced liver injury (DILI) or herb-induced liver injury(HILI) is an important and unresolved challenge. There is no consensus regarding the indications for corticosteroids for chronic DILI/HILI.AimsTo investigate the efficacy and safety of corticosteroid plus glycyrrhizin for patients with chronic DILI/HILI.MethodsThis was a randomised open-label trial. Eligible patients with causality assessment using the updated RUCAM were randomly assigned (1:1) either to the steroid treatment group (48-week stepwise dose reduction of methylprednisolone plus glycyrrhizin) or control group (glycyrrhizin alone). Liver biopsies were performed at baseline and at the end of the 48-week treatment period. The primary outcome was the proportion of patients with sustained biochemical response (SBR). The secondary outcomes were improvement in liver histology, time to biochemical normalisation and safety.ResultsOf 80 participants, 70 (87.5%) completed the trial. The patients were predominantly female (77.5%), aged >40 years (77.5%) and had a hepatocellular injury pattern of DILI (71.2%). Compared to the control group, the treatment group showed a higher proportion of SBR (94.3% vs. 71.4%, p = 0.023), shorter biochemical normalisation time and histological improvements in both histological activity and fibrosis. The DILI and HILI subgroups, as well as the autoimmune hepatitis (AIH)-like DILI and non-AIH-like subgroups, showed comparable responses. No severe adverse events were observed during the trial.ConclusionThis study provides the first clinical evidence that corticosteroid plus glycyrrhizin therapy for chronic DILI with or without AIH-like features can achieve both biochemical response and histological improvements with good safety. (ClinicalTrials.gov, NCT 02651350)

    03. Biology

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    Applications of Animal Models in Researching Hepatitis A

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    Hepatitis diseases are remaining in the list of significant threats to human health. Human hepatitis viruses are basically classified into six major hepatotropic pathogens—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV), and hepatitis G virus (HGV). Among these different forms of hepatotropic viruses, HAV as the leading cause of acute viral hepatitis is characterized as a kind of tiny ribonucleic acid virus that is linked to atopic disease. As we know, animal models have been instrumental in promoting understanding of complex host-virus interactions and boosting the advancement of immune therapies. So far, animal models such as nonhuman primates (NHPs) have enabled scientists to mimic and study the pathogenicities and host immune responses for hepatitis A infection. With the exception of chimpanzees and marmosets, animals like mice, pigs, guinea pigs, and tree shrews can also be selected as alternative animal models infected with HAV under laboratory conditions. In order to gain a better insight into hepatitis A pathogenesis and relevant contents, this chapter is mainly focused on the research progress in animal models of hepatitis A, and discusses the merits and demerits of these alternative models

    Using IS/IT to support the delivery of Chinese Medicine

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    This study investigated aspects of utilising IS/IT in Chinese Medicine practice in Australia. The research proposed that a more suitable synthesis should be adopted for the developments in this domain. Hence, the Chinese Medicine Inquiring System is a combination of the key concepts of Knowledge Management, Inquiring Systems and IS/IT

    Adverse reaction of Chinese herbal medicines.

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    Hin-Chung Chu.Thesis submitted in: July 2002.Thesis (M.Phil.)--Chinese University of Hong Kong, 2003.Includes bibliographical references (leaves 281-306).Abstracts in English and Chinese.Cover (English & Chinese version) --- p.I中文封面 --- p.IIAbstract (English version) --- p.III-IV中藥不良反應論文摘要 --- p.VAcknowledgements --- p.VIAbbreviations --- p.VII-VIIIPublication in press --- p.IXContent --- p.X-XVLists of Table --- p.XVIChapter Chapter 1 --- Introduction --- p.1-3Chapter Chapter 2 --- Chinese herbal medicines used in Hong Kong. --- p.4-15Chapter 2.1 --- Overview --- p.4-5Chapter 2.2 --- The Policy In Hong Kong -- Past And Present --- p.5-1Chapter 2.3 --- The Preparatory Committee on Chinese Medicine (PCCM) --- p.7-8Chapter 2.4 --- The Chinese Medicine Council of Hong Kong --- p.8-10Chapter 2.5 --- Development of Standards --- p.10Chapter 2.6 --- Development of Centres of Good Clinical Practice --- p.10-11Chapter 2.7 --- Establishment of a Good System of Education and Training --- p.11Chapter 2.8 --- Investigation of Suspected Herbal Toxicity Cases --- p.12-13Chapter 2.8.1 --- Herbal Safety Surveillance --- p.13-14Chapter 2.9 --- Conclusion --- p.14-15Chapter Chapter 3 --- Herbal medicines used in other countries --- p.16-45Chapter 3.1 --- Overview --- p.16Chapter 3.2 --- China --- p.16-19Chapter 3.3 --- Macau --- p.22-23Chapter 3.4 --- Taiwan --- p.23-26Chapter 3.5 --- Japan --- p.27-30Chapter 3.6 --- Singapore --- p.30-31Chapter 3.7 --- Australia --- p.31-34Chapter 3.8 --- Others Asian countries --- p.35Chapter 3.9 --- USA --- p.35-39Chapter 3.10 --- United Kingdom --- p.39-41Chapter 3.11 --- Europe --- p.41-43Chapter 3.12 --- Germany --- p.43-45Chapter Chapter 4 --- Adverse reaction -- General Aspect --- p.46-63Chapter 4.1 --- Overview --- p.46Chapter 4.2 --- Traditional Chinese medicine --- p.47-49Chapter 4.2.1 --- Compound Prescriptions to Reduce Toxicity --- p.50Chapter 4.2.2 --- Processing Of Chinese Herbs --- p.50-51Chapter 4.2.2.1 --- The Aims of Herbal Drug Processing --- p.51-52Chapter 4.2.2.2 --- The Methods of Herbal Drug Processing --- p.52Chapter 4.2.2.3 --- External processing (simple treatment by trimming) --- p.52-53Chapter 4.2.2.4 --- Water processing --- p.53-54Chapter 4.2.2.5 --- Fire processing --- p.54Chapter 4.2.2.6 --- Water-fire processing --- p.54-55Chapter 4.2.2.7 --- Other methods --- p.55Chapter 4.3 --- Practical Problem in Traditional Chinese Medicine --- p.55-57Chapter 4.4 --- Evaluation of herbal adverse reactions --- p.57Chapter 4.4.1 --- Type A reactions --- p.57Chapter 4.4.2 --- Type B reactions --- p.58Chapter 4.4.3 --- Type C reactions --- p.58Chapter 4.4.4 --- Type D reactions --- p.58Chapter 4.5 --- Chinese Proprietary medicine --- p.58-59Chapter 4.6 --- Potential Risks for Herbal Adverse Reaction --- p.59Chapter 4.6.1 --- Misidentification --- p.59-60Chapter 4.6.2 --- Lack of standardisation --- p.60Chapter 4.6.3 --- Contamination --- p.60Chapter 4.6.4 --- Incorrect preparation / dosage --- p.60Chapter 4.6.5 --- Excessive dosage --- p.60-61Chapter 4.6.6 --- Individual errors --- p.61Chapter 4.6.7 --- Individual response --- p.61Chapter 4.6.8 --- Unqualified Herbal Practitioner with Wrong Prescription --- p.61-62Chapter 4.6.9 --- Interaction with Western medicine --- p.62Chapter 4.6.10 --- Prolonged Usage --- p.62Chapter 4.6.11. --- Coexisting disease --- p.62-63Chapter 4.7 --- Conclusion --- p.63Chapter Chapter 5 --- "Substitution, Adulteration or Misusing with Toxic Herbs" --- p.64-84Chapter 5.1 --- Overview --- p.64-65Chapter 5.2 --- Adulteration by Guijiu --- p.65-68Chapter 5.3 --- Anticholinergic reactions Caused by --- p.69-74Chapter 5.4 --- Overdosage --- p.74Chapter 5.4.1 --- Overdose of Aconitine --- p.74-78Chapter 5.4.2 --- Overdose of Liquorice ('Gancao') --- p.78-80Chapter 5.4.3 --- Overdose of --- p.80Chapter 5.5 --- Misusing - Personal abuse --- p.80Chapter 5.5.1 --- --- p.80-81Chapter 5.6 --- Discussion --- p.81-84Chapter 5.7 --- Conclusion --- p.84Chapter Chapter 6 --- Chinese Patent Medicine - General Aspect --- p.85-112Chapter 6.1 --- Chinese Patent Medicine --- p.85Chapter 6.1.1 --- Introduction --- p.85-87Chapter 6.1.2 --- Herbal Injection and Infusion --- p.87-88Chapter 6.1.2.1 --- Variety & Processing --- p.88Chapter 6.1.2.2 --- Stabilization --- p.88-89Chapter 6.1.2.3 --- The Molecular Size --- p.89-90Chapter 6.1.3 --- Adverse Reactions Caused by Chinese Proprietary Medicines --- p.90Chapter 6.1.3.1 --- Aconitine poisoning --- p.90Chapter 6.1.3.2 --- Nan Lien Chui Fong Toukuwan' --- p.90-91Chapter 6.1.3.3 --- Jin Bu Huan' --- p.91Chapter 6.1.3.4 --- Baoyingdan' --- p.91Chapter 6.1.4 --- Heavy metals in CPM --- p.91Chapter 6.1.5 --- The Necessarity to Develop Randomise Herbal Clinical Trial. --- p.91-92Chapter 6.1.6 --- Recommendation --- p.92-93Chapter 6.1.7 --- Conclusion --- p.93-94Chapter 6.2 --- Adulteration by synthetic therapeutic substances --- p.95-104Chapter 6.2.1 --- The Experiences in China --- p.91-99Chapter 6.2.2 --- The Experiences in Hong Kong --- p.99-101Chapter 6.2.3 --- The Experience in Taiwan --- p.101-102Chapter 6.2.4 --- Discussion --- p.102-104Chapter 6.3 --- Oil of Wintergreen (Methyl salicylate) --- p.104-112Chapter 6.3.1 --- Overview --- p.104-111Chapter 6.3.2 --- Prevention --- p.111-112Chapter Chapter 7 --- Adverse effects of Ginseng. --- p.113-123Chapter 7.1 --- Overview --- p.113Chapter 7.2 --- Botany --- p.113-114Chapter 7.3 --- Pharmacological Effects --- p.114-115Chapter 7.4 --- Adverse reaction of Ginseng --- p.115Chapter 7.4.1 --- Overdosage --- p.115-116Chapter 7.4.2 --- Substitution with cheaper and more toxic herbs --- p.116-121Chapter 7.5 --- Drug - herb Interaction --- p.121-122Chapter 7.6 --- Conclusion --- p.123Chapter Chapter 8 --- Herbal Medicines With Cardiovascular Adverse Reactions --- p.124-123Chapter 8.1 --- Overview --- p.124Chapter 8.2 --- Hypertension --- p.124Chapter 8.3 --- Atherosclerosis --- p.124-125Chapter 8.4 --- Arrhythmias --- p.125-126Chapter 8.5 --- Cardic Failure --- p.126Chapter 8.6 --- Angia Pectoris --- p.126Chapter 8.7 --- Thromboembolic Disorders --- p.126-127Chapter 8.8 --- Discussion --- p.127-128Chapter 8.8.1 --- Herbal Medicine Used in Cardiovascular System --- p.131Chapter 8.8.1.1 --- Ginseng --- p.131-133Chapter 8.8.1.2 --- Ma huang (Ephedra sinica) --- p.133-136Chapter 8.8.1.3 --- Yellow oleander (Thevetia neriifolia) --- p.136-137Chapter 8.8.1.4 --- Stephania tetrandra --- p.137-138Chapter 8.8.1.5 --- Danshen (Salvia miltiorrhiza) --- p.138Chapter 8.8.1.8 --- Ginkgo biloba --- p.138-140Chapter 8.8.1.9 --- Dong Quai (Angelicae Sinensis) --- p.140-141Chapter 8.8.1.10 --- Licorice (Glycyrrhiza Glabra) --- p.141-143Chapter 8.8.1.11 --- Berberine --- p.143Chapter 8.8.2 --- Potential Problem Caused by Chinese Proprietary Medicine --- p.143-144Chapter 8.9 --- Other Herbal Adverse Effects And Drug Interaction --- p.144-145Chapter 8.10 --- Conclusion --- p.145Chapter Chapter 9 --- Review of the Adverse Reactions to herbal treatments of Obesity --- p.146-150Chapter 9.1 --- Overview --- p.146Chapter 9.2 --- Combined With Unknown medication --- p.146-147Chapter 9.3 --- Dietary Supplements and Herbal Preparations --- p.147-149Chapter 9.4 --- Conclusion --- p.149-150Chapter Chapter 10 --- Adverse Effects of CHM used for Diabetes --- p.151-159Chapter 10.1 --- Introduction --- p.151Chapter 10.2 --- Traditional Chinese medicine used in Diabetes --- p.151Chapter 10.3 --- Adverse Reaction of Alternative Diabetic Treatment --- p.152-158Chapter 10.4 --- Conclusion --- p.159Chapter Chapter 11 --- Review of Herbal Hepatotoxicity --- p.160-194Chapter 11.1 --- Introduction --- p.160-161Chapter 11.2 --- Drug-induced hepatic injury --- p.161-163Chapter 11.3 --- Types of Liver Injury --- p.163Chapter 11.3.1 --- Pyrrolizidine alkaloid (PA) --- p.163Chapter 11.4 --- Hepatotoxicity Herbs --- p.163Chapter 11.4.1 --- Tripterygium wilfordii --- p.163-164Chapter 11.4.2 --- Rhizoma Discoreae Bulbiferae --- p.164-165Chapter 11.5 --- Consumption of Insect herbs --- p.165Chapter 11.6 --- Hepatotoxicity Cause by Chinese Proprietary Medicine --- p.165-166Chapter 11.6.1 --- Jin Bu Huan --- p.166-168Chapter 11.6.2 --- Chi R Yun (Breynia officinalis) --- p.168Chapter 11.6.3 --- Sho-saiko-to --- p.168-169Chapter 11.6.4 --- Shou-Wu-Pian --- p.169-171Chapter 11.7 --- Importance of Drug-Herb and Herb-Herb Interactions --- p.171-172Chapter 11.8 --- Diagnosis of Herbal Hepatotoxicity --- p.172-173Chapter 11.9 --- Recomandation --- p.173-174Chapter 11.10 --- Conclusion --- p.175Table --- p.176-180Chapter Chapter 12 --- Review of Herbal Nephropathy --- p.181-194Chapter 12.1 --- Introduction --- p.181Chapter 12.2 --- Aristolochia acids (AA) --- p.181-183Chapter 12.2.1 --- Intoxication of Aristolochia in Worldwide --- p.183-184Chapter 12.2.2 --- Morphological findings --- p.184-185Chapter 12.2.3 --- Carcinogenic --- p.185-187Chapter 12.3 --- MuTong (Aristolochia manshuriensis) --- p.187-188Chapter 12.4 --- Ma-dou-ling (Fructus Aristolochiae) --- p.188Chapter 12.5 --- Tripterygium wilfordii --- p.188-189Chapter 12.6 --- Gastrodia Elata --- p.189Chapter 12.7 --- Licorice (Glycyrrhiza glabra) --- p.190-191Chapter 12.8 --- Hippocampus (Sea Horse) --- p.191Chapter 12.9 --- Milabris Phanalerata --- p.191-192Chapter 12.10 --- Chinese Proprietary Medicine --- p.192-193Chapter 12.11 --- Conclusion --- p.193-194Chapter Chapter 13 --- Adverse Reaction of Herbal Medicine in Dermatology. --- p.195-217Chapter 13.1 --- Overview --- p.195-196Chapter 13.2 --- Chinese Herbal Medicine Used in Psoriasis --- p.196Chapter 13.2.1 --- Tripterygium wilfordii --- p.197Chapter 13.2.2 --- Radix Angelicae pubescentis and Radix Angelicae dahuricae --- p.197-198Chapter 13.2.3 --- Radix macrotomiae seu Lithospermi Injection --- p.198Chapter 13.3 --- Chinese Herbal Decoction For Atopic Dermatitis --- p.198-200Chapter 13.3.1 --- Tea Extracts --- p.200-201Chapter 13.4 --- Potential Adverse Effect with Herbal Medicine --- p.201Chapter 13.4.1 --- Allergic skin reactions --- p.201-202Chapter 13.4.2 --- Stevens-Johnson syndrome --- p.202Chapter 13.4.3 --- Photosensitization --- p.202-204Chapter 13.4.4 --- Pellagra --- p.204Chapter 13.4.5 --- Hepatotoxic Effects --- p.204-205Chapter 13.4.6 --- Others Adverse Reaction --- p.205Chapter 13.4.7 --- Potential Adverse Reaction Caused by Interactions --- p.205Chapter 13.5 --- Potential Adverse Reaction Caused by Contamination of Herbal Product --- p.206Chapter 13.5.1 --- Herbal creams adulterated with corticosteroids --- p.206-207Chapter 13.5.2 --- Arsenic dermatoses --- p.207Chapter 13.5.3 --- Mercury poisoning --- p.207-208Table --- p.208-211Chapter 13.6 --- Dermatological Adverse Reaction Caused by Herbs --- p.211Chapter 13.7 --- Contact Dermatitis Caused by CPM --- p.211-212Chapter 13.7.1 --- Liushenwan' --- p.211-212Chapter 13.7.2 --- Heiguiyou' --- p.212Chapter 13.7.3 --- 101 Hair Regrowth Liniment' --- p.212-213Chapter 13.7.4 --- Zhenggushui' --- p.213Chapter 13.7.5 --- Tiedayaoiing' --- p.213-214Table --- p.214-215Chapter 13.8 --- Non-dermatological adverse effects of systemic herbal treatments used for dermatological conditions --- p.215-216Chapter 13.9 --- Conclusion --- p.216-217Chapter Chapter 14 --- "Chinese Herbal Medicine in Pregnancy, Infants & Children," --- p.218-229Chapter 14.1 --- Overview --- p.218-219Chapter 14.2 --- Asian Cultures for Pregnancy --- p.219-223Chapter 14.3 --- Teratogenic Herbs --- p.224-225Chapter 14.4 --- Chinese proprietary medicines --- p.225Chapter 14.4.1 --- "“Tse Koo Choy""" --- p.225-226Chapter 14.4.2 --- "“Lu Shen Wan""" --- p.226Chapter 14.4.3 --- "“Po Ying Pills""" --- p.226-227Chapter 14.4.4 --- """Jin Bu Huan Toxicity"" in Children" --- p.227Chapter 14.6 --- Topical Preparations --- p.227-228Chapter 14.7 --- Dietary supplement --- p.228-229Chapter 14.8 --- Conclusion --- p.229Chapter Chapter 15 --- Heavy metals poisoning in traditional Chinese medicines. --- p.230-251Chapter 15.1 --- Introduction --- p.230-232Chapter 15.2 --- LEAD --- p.232Chapter 15.2.1 --- Overview --- p.232Chapter 15.2.2 --- Poisoning Cases of Boa Ning Dan --- p.233-235Chapter 15.2.3 --- Lead Poisoning in Worldwide --- p.235-238Chapter 15.3 --- MERCURY --- p.238Chapter 15.3.1 --- Overview --- p.238-239Chapter 15.3.2 --- Cinnabar --- p.239-240Chapter 15.3.3 --- Presentation --- p.240-241Chapter 15.3.4 --- Poisoning Cases --- p.241-242Chapter 15.4 --- ARSENIC --- p.242Chapter 15.4.1 --- Overview --- p.242-243Chapter 15.4.2 --- Arsenic toxicity --- p.243-244Chapter 15.4.3 --- The toxicologic mechanisms of inorganic arsenic --- p.244-246Chapter 15.4.4 --- Poisoning Cases --- p.246Chapter 15.4.5 --- Discussion --- p.247-248Chapter 15.5 --- Conclusion --- p.248Table --- p.249-251Chapter Chapter 16 --- Herb - Drug Interactions --- p.252-269Chapter 16.1 --- Overview --- p.252-254Chapter 16.2 --- Effects of Herb-drug interactions --- p.255Chapter 16.2.1 --- Gastrointestinal system --- p.255-256Chapter 16.2.2 --- Cardiovascular system --- p.256Chapter 16.2.3 --- Central nervous system --- p.257Chapter 16.2.4 --- Endocrine system --- p.257Chapter 16.3 --- Reason regard to herb-drug interactions --- p.257Chapter 16.3.1 --- Lack of Knowledge About Herbs --- p.257Chapter 16.3.2 --- Mislabelling or Adulteration --- p.258Chapter 16.3.3 --- Lack of Patient Communication About Use of Botanicals --- p.258Chapter 16.3.4 --- Lack of Practitioner Knowledge About Potential Interactions --- p.258Chapter 16.4 --- Metabolism of Herb-Drug Interaction --- p.258-259Chapter 16.5 --- Pharmacologic Interactions --- p.259-260Chapter 16.5.1 --- Interaction with Antibiotics --- p.260Chapter 16.5.2 --- Interaction with Nonsteroidal Anti-inflammatory Drugs --- p.260-261Chapter 16.5.3 --- Interaction with Sedatives --- p.261-262Chapter 16.5.4 --- Interaction with Anticoagulants --- p.262-263Chapter 16.5.5 --- Interaction with Anti-hypertensives and Diuretics --- p.263Chapter 16.5.6 --- Interaction with Spironolactone --- p.264Chapter 16.5.7 --- Interaction with Corticosteroids and Cyclosporine --- p.264-265Chapter 16.5.8 --- Interaction with Estrogen Replacement Therapy --- p.265Chapter 16.5.9 --- Interactions Between Natural Product and Drug --- p.265-266Chapter 16.6 --- Herb-to-Herb Interactions --- p.266-267Chapter 16.7 --- Conclusion --- p.268-269Chapter Chapter 17 --- Recommendation --- p.270-264Chapter 17.1 --- Overview --- p.270Chapter 17.2 --- The need to evaluate the clinical effectiveness of traditional Chinese medicine --- p.270-271Chapter 17.3 --- For the Pharmaceutical Industries --- p.211-212Chapter 17.4 --- For the physicians & patient --- p.272-274Conclusion --- p.274Chapter Chapter 18 --- Conclusion --- p.275-280Chapter Chapter 19 --- Reference --- p.281-30

    Small molecule compounds, active ingredients of TCM, as novel therapeutics for eosinophilic esophagitis

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    Eosinophilic Esophagitis (EoE), a chronic inflammatory condition of the esophagus, characterized by esophageal dysfunction and eosinophilic inflammation. Current treatments for EoE include dietary elimination and swallowed steroids. Recently, Dupixent was approved for the treatment of EoE, but it has side effects such as eye inflammation and eczema. Traditional Chinese Medicine (TCM) practice has been used to improve GI symptoms in EoE patients. Two key active ingredients of a TCM formula, 7,4’-Dihydroxyflavone (DHF) and Berberine (BBR), have shown remarkable results in treating EoE. To understand the role of two active ingredients in EoE, different experimental models were used. First, a computational model to test the effect of DHF on EoE targets. 29 common targets including TNF-α, IL6, IL1β, IL-8, CCND, and MAPK1 were found, and these targets were validated ex-vivo on cultured human esophagus biopsy specimens from EoE patients. In another approach, we used a peanut-induced murine model of EoE to understand the underlying mechanisms associated with BBR-N protection in developing EoE. BBR-N treatment showed a reduction in the number of eosinophils in the esophagus, decreased epithelial thickening, and reduced fibrosis and fibronectin as compared to sham mice. BBR-N treatment led to the inhibition of peanut-specific IgE and prevented mast cell degranulation and modulated gut microbiome. Our results conclude the potential of small molecule compounds, DHF and BBR-N, derived from a TCM formula in treating EoE. This study provides insight into the molecular mechanisms underlying multi-targeted benefits of DHF and BBR-N in treating EoE and further facilitate more effective clinical trials

    Leukocyte Subsets in the Peripheral Blood and Spleen of Gastrointestinal Cancer Patients

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    In 2022, an estimated 62,210 people will be diagnosed with pancreatic ductal adenocarcinoma (PDAC) and approximately 49,830 will die from the disease. Current treatment strategies for gastrointestinal (GI) cancer patients, such as PDAC, have shown limited benefit, suggesting the need to develop novel, multimodality therapeutic approaches. Adoptive cellular therapy (ACT) using autologous tumor infiltrating lymphocytes (TILs) has shown efficacy in patients with melanoma; however, this approach is costly and requires extensive cell culture for sufficient numbers of T-cells for infusion. GI cancer patients with borderline resectable disease, whose primary tumor is adjacent to the splenic vasculature, can sometimes undergo a splenectomy as standard of care as the pancreas and spleen share the same blood supply, making the spleen a potential site for metastasis. The spleen provides an unutilized source of lymphocytes with potential utility for ACT, but few studies have examined the immune profile, or the effect of neoadjuvant chemotherapy (NCT) on the immune profile, in the spleen and peripheral blood (PB) in cancer patients. To address these questions, we undertook flow cytometric and clustering analyses on leukocyte populations, and the impact of NCT on patient immunity, in the spleens and PB of cancer patients, and compared these to both normal donors and patients with benign GI tumors. These studies provided several novel observations: first that the spleen is a rich source of CD8+PD-1+ T-cells with low expression of checkpoint proteins and potential utility for ACT. Secondly, we observed significant differences in the frequency and phenotype of myeloid-derived suppressor cells (MDSCs) in the PB and spleen of GI cancer patients as compared to the PB of normal donors, some of which were specific to the tissue type or source analyzed. Third, we report that, ~6 weeks post NCT, the immune profile of NCT treated cancer patients has recovered; this suggests that post-surgical resection patients may be more responsive to immune intervention. In addition, we report preliminary peripheral studies during which we assessed the function of CD8+PD-1+ T-cells from the spleens of GI cancer patients

    Characterization of CD8+ T-CELL populations of the human peripheral blood

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    Tese de doutoramento (Registo), Univ. de Lisboa, nº 28, 2009, (Immunologie), Université René Descartes - Paris V, 2009Following antigenic challenge, naïve CD8+ T lymphocytes undergo severalchanges, including the expression of cell-surface molecules. In humans, theassociation of CCR7, CD45RA, CD27 and CD28 is widely used to discriminate areproducible set of functionally different subpopulations of CD8+ T cells. However,the prevailing data concerning the description of these subsets remainsfragmentary, since a multitude of studies used a different and limited set of surfacemarkers. Hence, some CD8+ T-cell subsets are still not clearly established,especially within the CCR7 CD45RA+ and CCR7 CD45R0+ compartments, andthe correspondent differential roles and lineage relationships remain undisclosed.The present study aims to define a predictable and precise correlationbetween particular cell surface markers and CD8+ T-cell functional properties. Weassociated CCR7, CD45RA, CD27 and CD28 expression levels to subdivide CD8+T cells into fourteen different cell types. These populations were further isolatedand gene expression of 18 genes was assessed, simultaneously, in single-cells bya novel multiplex RT-PCR method we developed. Our results demonstrate that thedifferent subpopulations display distinct and characteristic gene co-expressionpatterns, reproducible between donors. CD45RA expression is required to definethe naïve subset, but does not discriminate functionally different populations ofprimed cells. In contrast, gene expression profiles of CCR7-CD8+ T cells correlatesignificantly to CD27 expression levels and CD27/CD28 co-expression, and ahierarchy of activation stages could be established as follows: naïve < CD27high <CD27+CD28+ < CD28+CD27 < CD27+CD28 < CD27 CD28 . Surprisingly, wefound that CD45RA+ and CD45RA cells of each of these subsets had the samegene expression patterns at both qualitative and quantitative level. Importantly, weidentified minor subsets displaying characteristics of recent activation that could befound in both CD45RA+ and CD45RA compartments. These findings stronglysuggest that differentiation of naïve CD8+ T cells into effectors does notnecessarily imply CD45RA downregulation. Furthermore, they describe novelCD8+ T cell subsets and establish a correlation between surface phenotype andcell function, which helped to identify homogeneous populations
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