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Overall survival,late mortality,and cancer-directed surgery among children and adolescents with ultra-rare pediatric pancreatoblastoma in the United States,1975-2018

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Journal of Pancreatology 2023年第2期6卷 61-66页

作者： Peiyi Li Yujia Kong Lin Wan Jing Guo Weimin Li Hui Zhang Guang Yang Bo Zhang Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuanChina Laboratory of Anesthesia and Critical Care Medicine National-Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuanChina Department of Public Health Weifang Medical UniversityWeifangShandongChina Department of Pediatrics First Medical CenterChinese PLA General HospitalBeijingChina Senior Department of Pediatrics Seventh MedicalCenterPLA General HospitalBeijingChina Department of Health Policy and Management School of Public HealthPeking UniversityBeijingChina Department of Respiratory and Critical Care Medicine West China HospitalSichuan UniversityChengduSichuanChina Institute of Respiratory Health Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengduSichuanChina Department of Preventive Medicine Feinberg School of MedicineNorthwestern UniversityChicagoIL The Second School of Clinical Medicine Southern Medical UniversityGuangzhouChina Department of Neurology Boston Children’s HospitalHarvard Medical SchoolBostonMA biostatistics and Research Design Center Institutional Centers for Clinical and Translational ResearchBoston Children’s HospitalHarvard Medical SchoolBostonMA

Background:Pediatric pancreatoblastoma is an extremely rare malignant tumor,posing diagnostic and treatment difficulties for pediatric *** the Surveillance,Epidemiology,and End Results(SEER)database,we present an up-to-date report of the epidemiology,clinicopathological features,survival rates,and prognosis of pancreatoblastoma in pediatric ***:All pediatric patients diagnosed with pancreatoblastoma between 1975 and 2018 were identified in the SEER regis-tries(SEER 8 registries and SEER 17 registries).We conducted a survival analysis to assess overall survival and 1-and 5-year late mortality *** statistics and log-rank test were ***:A total of 22 children and adolescents with pancreatoblastoma were *** this cohort,12 of 22 were male(54.55%),14 were White(63.64%),and 11 were diagnosed between the ages of 1 and 4 years(50.0%).Among the 22 patients,11(50.0%)had distant metastases,whereas 7(31.82%)had localized,and 4(18.18%)had a regional disease.A total of 5 children and adolescents died during the study period,with cumulative survival rates of 14 of 17(82.35%)and 10 of 11(90.95%)among 1-and 5-year survivors,***-directed surgery was significantly associated with an increased life expectancy(log-rank test,P=.018).Conclusion:Pediatric pancreatoblastoma is a rare *** that underwent surgery had a greater likelihood of overall survival and reduced late mortality.

关键词： Mortality Overall survival Pancreatic cancer surgery Pancreatoblastoma Pediatric pancreatic cancer

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GSTM1, GSTT1 and CYP1A1 polymorphism and risk of oral cancer： a case-control study in Jakarta population, Indonesia

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中国口腔颌面外科杂志 2008年第B5期6卷 155-155页

作者： Rahmi Amtha Cheong S. Ching Rosnah B. Zain Ishak A. Razak Bastaman B Boedi O. Roeslan Walta Gautama Denny J. Purwanto Oral Cancer Research and Coordinating Center (OCRCC) University of Malaya Kuala Lumpur Oral Medicine Department Trisakti University Indonesia Cancer Research Initiatives Foundation (CARIF) Subang Jaya Malaysia Community Medicine and biostatistics Department University of Indonesia Biochemistry Department Trisakti University Indonesia Surgical Oncology Department Dharmais Hospital National Cancer Center Indonesia

Purpose: T o investigate the genetic polymorphism GSTMI, GSTTl and CYPlAl and the risk of oral cancer in a Jakarta population。Methods: A total of 81 cases and 162 controls matched for age and sex were selected from 5 hospitals in Jakarta。Sociodemographic data and peripheral blood samples were collected from consented individuals。Samples were analyzed using PCR-RFLP methods。Conditional logistic regression analysis was performed to obtain the risk of oral cancer with GSTMI, GSTTl and CYPlAl polymorphisms。Results: GSTMl and GSTTl null was slightly overrepresented among cases (60.5% and 45.7% respectively) compared to controls (55.6% and 41.4% respectively), however no statistically significant differences were observed between cases and controls。In contrast, the distribution of CYP 1A 1 polymorphism was higher among controls compared to cases (52.5 % versus 42.4 %)。Although not statistically significant, the Odds ratios of null GSTMI and GSTTI genotypes were slightly higher compared to the wild type genotypes (OR 1.19, 95% CI 0.70-2.02 and OR 1.19, 95% CI 0.72-2.05 respectively)。However, the statistical analysis indicates that CYPIAI polymorphism does not increase the risk of oral cancer (OR 0.70, 95% 0.39-1.25)。Conclusion: Genetic polymorphisms of GSTMI, GSTTI and CYPIAI alone may not increase the risk of oral cancer in Jakarta population。

关键词：口腔癌控制方法治疗方法印尼医疗卫生事业

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Remediation of Hepatotoxic Effect of Tamoxifen with Ginger in Rat Model

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Journal of Pharmacy and Pharmacology 2022年第3期10卷 79-86页

作者： Vanditha.S Princy Louis Palatty Malini Eapen Thennavan.A Manjeshwar.S.Baliga Greeshma.C.Ravindran Department of Pharmacology Amrita School of MedicineAmrita Vishwa VidyapeethamKochiIndia Department of Pathology Amrita School of MedicineAmrita Vishwa VidyapeethamKochiIndia Veterinary Medicine Department Amrita School of MedicineAmrita Vishwa VidyapeethamKochiIndia Mangalore Institute Of Oncology MangaloreIndia Department of biostatistics Amrita School of MedicineAmrita Vishwa VidyapeethamKochiIndia

Background:Tamoxifen is a non-steroidal oestrogen receptor *** has strong anti-estrogenic activity on oestrogen receptor 2 in the breast *** is the treatment of choice in breast cancer cases following surgery and radiotherapy,it is the most potent weapon against breast *** stages of hormone-dependent breast cancer are currently treated with ***-term tamoxifen therapy may cause hepatotoxicity which would perclude the use of *** this study was done to determine whether ginger has a role in protecting liver toxicity caused by ***:Twenty female albino rats(SD)were divided into 4 *** group formed of five rats:Group I:Serves as control group received normal rodent diet and water,GroupⅡ:Received ginger powder(200 mg/kg)dissolved in normal saline,orally daily for 6 weeks,GroupⅢ:received TAM at a dose of 20 mg/kg daily for 6 weeks orally GroupⅣ:Received TAM(20 mg/kg)then after 2 hrs they are orally given Ginger powder(200 mg/kg)daily for 6 ***:Tamoxifen 20 mg/kg/day caused hepatotoxicity in *** ginger is added to tamoxifen there is no development of hepatotoxic features like:marked sinusoidal congestion in the lobules and lab parameters showed decrease in serum AST and ALT levels when compared to tamoxifen group ***:Ginger supplementation would reduce the incidence of hepatotoxicity&related adverse drug reactions among breast cancer patient on therapy.

关键词： Breast cancer tamoxifen ginger raised liver enzyme levels hepatotoxicity hepatic sinusoidal congestion

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自适应辅助通气的潮气量决定因素：一项多中心观察研究

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麻醉与镇痛 2010年第1期6卷 92-98页

作者： Dave A. Dongelmans Denise P. Veelo Alexander Bindels Jan M. Binnekade Kees Koppenol Matty Koopmans Joke C. Korevaar Michael A. Kuiper Marcus J. Schultz 杨婷(译) 姚尚龙(校) Department of Intensive Care Medidne University of Amsterdam Amsterdam The Netherlands Department of Anesthesiology Academic Medical Center University of Amsterdam Amsterdam The Netherlands Department of Intensive Care Medicine Catharina Hospital Eindhoven Eindhoven The Netherlands Department of Intensive Care Medi- cine Medical Centre Leeuwarden Leeuwarden The Netherlands Department of Clinical Epidemiology and biostatistics Academic Medical Center University of Amsterdam Amsterdam The Netherlands HERMES Critical Care Group Amsterdam The Netherlands Laboratory for Experimental Intensive Care and Anesthesiology( L. E. I. C. A) Academic Medical Center University of Amsterdam Amsterdam The Netherlands 不详

引言在本研究中，我们在心胸外科手术后患者中观察了自适应辅助通气（adaptive support ventilation，ASV）。我们明确了在这种微处理器控制机械通气模式下的潮气量（tidal volumes，VT）和潮气量的影响因素。方法这是一项在荷兰的三家... 详细信息

引言在本研究中，我们在心胸外科手术后患者中观察了自适应辅助通气（adaptive support ventilation，ASV）。我们明确了在这种微处理器控制机械通气模式下的潮气量（tidal volumes，VT）和潮气量的影响因素。方法这是一项在荷兰的三家加强监护病房进行的为期5个多月的前瞻性、多中心观察研究。机械通气的数据在患者来到加强监护病房后的稳定状态下收集。结果数据来自心胸外科术后的连续346例患者：其中262例患者采用自适应辅助通气模式，84例患者采用压力控制机械通气模式。在ASV模式下，每实际公斤体重（ABW）的VT（mean±SD）为7．1±1．6ml，每理想公斤体重（IBW）的、VT为8.3±1.5ml。而在恰当设定体重（SBW）（如，理想体重IBW）的患者，VT为8．1±1．4ml／kg。在压力控制机械通气模式下，VT为7．3±1．4ml／kgIBW（P〈0．001vsASV）。多变量logistic回归分析表明ASV模式的VT仅依赖于两个参数：呼吸频率和设定体重的正确性。结论ASV模式的VT依赖于两个参数：呼吸频率和设定体重的正确性。第一个因素并没有重要的临床意义，因为呼吸频率是由微处理器自动选择的。第二个因素在临床上非常重要，因为这是受操作者影响的唯一因素。我们的数据表明了在ASV模式下设定正确体重的重要性。在ASV模式下，绝大多数患者的VT〉8ml／kg IBW。未来还需要进行随机临床试验来将ASV和其他通气模式进行比较。

关键词：辅助通气潮气量自适应多中心 logistic回归分析机械通气模式微处理器控制理想体重

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非心脏手术围手术期使用β阻断剂的证据有多强?对一系列随机对照试验的系统性回顾与荟萃分析

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世界核心医学期刊文摘（心脏病学分册） 2006年第1期2卷 17-17页

作者： Devereaux P. J. Beattie W. S. Choi P. T.-L. 朱冰坡 Department of Clinical Epidemiology and biostatistics McMaster University Health Sciences Centre 1200 Main Street West Hamilton Ont. L8N 3Z5 Canada

Objective: To determine the effect of perioperative βblocker treatment in patients having non-cardiac surgery. Design: Systematic review and meta-analysis. Data sources: Seven search strategies, including searching two bibliographic databases and hand searching seven medical journals. Study selection and outcomes: We included randomised controlled trials that evaluated βblocker treatment in patients having non-cardiac surgery. Perioperative outcomes within 30 days of surgery included total mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive heart failure, hypotension needing treatment, bradycardia needing treatment, and bronchospasm. Results: Twenty two trials that randomised a total of 2437 patients met the eligibility criteria. Perioperative βblockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 0.44(95%confidence interval 0.20 to 0.97, 99%confidence interval 0.16 to 1.24) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest. Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies. The individual safety outcomes in patients treated with perioperative βblockers showed a relative risk for bradycardia needing treatment of 2.27(95%CI 1.53 to 3.36, 99%CI 1.36 to 3.80) and a nominally statistically significant relative risk for hypotension needing treatment of 1.27(95%CI 1.04 to 1.56, 99%CI 0.97 to 1.66). Conclusion: The evidence that perioperative βblockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn.

关键词：非心脏手术患者随机对照试验系统性回顾围手术期 β阻断剂荟萃分析致死性心肌梗死证据检索策略非致死性

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Breast Cancer Risk Genes-Association Analysis in More than 113,000 Women

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四川生理科学杂志 2021年第1期43卷 7-7页

作者： Leila Dorling The authors' affiliations are as follows: the Centre for Cancer Genetic Epidemiology Departments of Public Health and Primary Care (L.D. S. Carvalho J.A. K.A.P. Q.W. M.K.B. J.D. B.D. N. Mavaddat K. Michailidou A.C.A. P.D.P.P. D.F.E.) and Oncology (C.L. P.A.H. C. Baynes D.M.C. L.F. V.R. M. Shah P.D.P.P. A.M.D. D.F.E.) University of Cambridge Cambridge the Centre for Genomic and Experimental Medicine MRC Institute of Genetics and Molecular Medicine (A. Campbell D.J.P.) and the Centre for Cognitive Ageing and Cognitive Epidemiology Department of Psychology (D.J.P.) University of Edinburgh the Cancer Research UK Edinburgh Centre (D.A.C. J.F.) and the Usher Institute of Population Health Sciences and Informatics University of Edinburgh Medical School (A. Campbell J.F.) Edinburgh the Divisions of Informatics Imaging and Data Sciences (E.F.H.) Cancer Sciences (A. Howell) Population Health Health Services Research and Primary Care (A. Lophatananon K. Muir) and Evolution and Genomic Sciences School of Biological Sciences (W.G.N. E.M.V. D.G.E.) University of Manchester the NIHR Manchester Biomedical Research Unit (E.F.H.) and the Nightingale Breast Screening Centre Wythenshawe Hospital (E.F.H. H.I.) Academic Health Science Centre and North West Genomics Laboratory Hub and the Manchester Centre for Genomic Medicine St. Mary's Hospital Manchester University NHS Foundation Trust (W.G.N. E.M.V. D.G.E.) Manchester the School of Cancer and Pharmaceutical Sciences Comprehensive Cancer Centre Guy's Campus King's College London London (E.J.S.) the Institute of Cancer and Genomic Sciences University of Birmingham Birmingham (I.T.) and the Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre University of Oxford Oxford (I.T.) - all in the United Kingdom the Human Genotyping-CEGEN Unit Human Cancer Genetic Program (A.G.-N. M.R.A. N.Á. B.H. R.N.-T.) and the Human Genetics Group (V.F. A.O. J.B.) Spanish National Cancer Research

Background:Genetic testing for breast cancer susceptibility is widely used,but for many genes,evidence of an association with breast cancer is weak,underlying risk estimates are imprecise,and reliable subtype-specific risk estimates are ***:We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 *** separate analyses for protein-truncating variants and rare missense variants in these genes,we estimated odds ratios for breast cancer overall and tumor *** evaluated missense-variant associations according to domain and classification of pathogenicity.

关键词： cancer Breast Cancer

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一种miRNA标记在胶质瘤侵袭性表型的确定与预后评估中的价值(英文)

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中华神经外科疾病研究杂志 2014年第5期13卷 433-433页

作者： Barbano R Palumbo O Pasculli B Galasso M Volinia S D'Angelo V Icolaro N Coco M Dimitri L Graziano P Copetti M Valori VM Maiello E Carella M Fazio VM Parrella P Laboratory of Oncology "IRCCS Casa Sollievo della Sofferenza" Laboratory of Genetics "IRCCS Casa Sollievo della Sofferenza" Department of Biosciences Biotechnology and BiopharmaceuticsUniversity of Bari "Aldo Moro" LTTA Department of MorphologySurgery and Experimental MedicineHuman Anatomy BranchUniversity of Ferrara Department of Neurosurgery "IRCCS Casa Sollievo della Sofferenza " Department of Pathology "IRCCS Casa Sollievo della Sofferenza" Unit of biostatistics "IRCCS Casa Sollievo della Sofferenza" Department of Oncology "IRCCS Casa Sollievo della Sofferenza" CIR Laboratory for Molecular Medicine and Biotechnology University Campus Biomedico

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus,there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA( miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours( 2 WHO grade III and 22 glioblastomas) by using the Affymetrix Gene Chip miRNA Array v. 1. 0. A relative quantification method( RT-q PCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas( TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade ***-q PCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme( GBM) and Lower Grade Glioma( LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover,in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses( HR 1. 19,P = 0. 04,and HR 1. 18,P = 0. 029 respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.

关键词：神经外科学疾病临床研究医学

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Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy： A National Multicenter Study in China

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Chinese Medical Journal 2017年第22期130卷 2661-2665页

作者： Hua Yang Xiao-Chuan Li Chen Yao Jing-He Lang Hang-Mei Jin Ming-Rong Xi Gang Wang Lu-Wen Wang Min Hao Yan Ding Jie Chen Jian-Qing Zhang Lu Han Cheng-Xiu Guo Xiang Xue Yan Li Jian-Hua Zheng Man-Hua Cui Huai-Fang Li Guang-Shi Tao Long Chen Su-Min Wang An-Wei LU Ze-Hua Huang Qing Liu Ya-Li Zhuang Xiang-Hua Huang Gen-Hai Zhu Ou-Ping Huang Li-Na Hu Mu-Jun Li Hong-Lin Zhou Jing-Hui Song Lan Zhu Department of Obstetrics and Gynecology Peking Union Medical College Hospital Beijing 100730 China Department of biostatistics Peking University Clinical Research Institute Peking University First Hospital Beijing 100871 China Department of Obstetrics and Gynecology Zhejiang University Affiliated Obstetrics and Gynecology Hospital Zhejiang Hangzhou 310006 China Department of Obstetrics and Gynecology West China Second Hospital of Sichuan University Cbengdu Sichuan 610041 China Department of Obstetrics and Gynecology The First People's Hospital of Foshan City Foshan Guangdong 528010 China Department of Obstetrics and Gynecology Maternal and Child Health Hospital of Henan Province Zhengzhou Henan 450052 China Department of Obstetrics and Gynecology The Second Hospital of Shanxi Medical University Datong Shanxi 030001 China Department of Obstetrics and Gynecology The First Affiliated Hospital of Xinjiang Medical University Urumchi Xinjiang 830000 China Department of Obstetrics and Gynecology People's Hospital of Fujian Province Fuzhou Fujian 350000 China Department of Obstetrics and Gynecology Qinghai Red Cross Hospital Xining Qinghai 810000 China Department of Obstetrics and Gynecology Dalian Maternity Hospital Dalian Liaoning 116021 China Department of Obstetrics and Gynecology Tianjin Central Maternity Hospital Tianjin 300100 China Department of Obstetrics and Gynecology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi 710061 China Department of Obstetrics and Gynecology General Hospital of Ningxia Medical University Yinchuan Ningxia Hui Autonomous Region 750003 China Department of Obstetrics and Gynecology The First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang 150007 China Department of Obstetrics and Gynecology The Second Hospital of Jilin University Changchun Jilin 130041 China Department of Obstetrics and Gynecology Shanghai Tongji Hospital Shanghai 200065 China Department of Obstetrics and Gynec

Background： The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. Methods： A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. Results： The proportion of postoperative malignancy after morcellation application was 0.18% （62/33,723） for patients who underwent laparoscopic myomectomy. Nearly 62.9% （39/62） of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 （37.1%） patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 （61.3%） patients had detectable endometrial stromal sarcoma, 13 （21.0%） had detectable uterine leiomyosarcoma, only 3 （3.2%） had detectable carcinosarcoma, and 5 （8.1%） patients with leiomyoma had an undetermined malignant potential. Conclusions： The proportion of malignancy is low after using moreellation in patients who undergo laparoscopie myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.

关键词： Laparoscopic Myomectomy Morcellation Sarcoma

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Obesity alters pathology and treatment response in inflammatory disease

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四川生理科学杂志 2022年第3期44卷 446-446页

作者： Sagar P Bapat NOMIS Center for Immunobiology and Microbial Pathogenesis The Salk Institute for Biological Studies La Jolla CA USA Gene Expression Laboratory The Salk Institute for Biological Studies La Jolla CA USA Medical Scientist Training Program University of California San Diego La Jolla CA USA Department of Laboratory Medicine University of California San Francisco San Francisco CA USA Department of Microbiology and Immunology University of California San Francisco San Francisco CA USA Diabetes Center University of California San Francisco San Francisco CA USA Medical Scientist Training Program University of California San Francisco CA USA Division of Pulmonary Critical Care Allergy and Sleep Department of Medicine University of California San Francisco San Francisco CA USA School of Pharmaceutical Sciences Xiamen University Xiamen China Department of Dermatology University of California San Diego La Jolla CA USA Department of surgery University of California San Francisco San Francisco CA USA Department of Medicine University of California San Francisco San Francisco CA USA Sandler Asthma Basic Research Center University of California San Francisco San Francisco CA USA School of Medicine Wake Forest University Winston–Salem NC USA Department of Dermatology Icahn School of Medicine at Mount Sinai New York NY USA Lung Biology Center Department of Medicine University of California San Francisco San Francisco CA USA Department of Biomedical Science Graduate School Kyungpook National University Kyungpook National University Hospital Daegu South Korea Department of Dermatology University of California San Francisco San Francisco CA USA Department of Pathology University of California San Francisco San Francisco CA USA Department of Internal Medicine Division of Pulmonary Critical Care and Sleep Medicine University of Kentucky Lexington KY USA Pulmonary Critical Care Section Department of Medicine Veterans Affairs San Diego Hea

Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune,allergic and inflammatory *** evidence indicates that obesity and metabolic disease can also influence the immune system1-7,although the mechanisms and effects on immunotherapy outcomes remain largely ***,using two models of atopic dermatitis,we show that lean and obese mice mount markedly different immune *** converted the classical type 2 T helper(TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 *** also observed divergent responses to biologic therapies targeting TH2 cytokines,which robustly protected lean mice but exacerbated disease in obese ***-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ(PPARγ)in TH2 cells from obese mice relative to lean mice.

关键词： dermatitis inflammatory allergic

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Genetic mechanisms of critical illness in Covid-19

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四川生理科学杂志 2020年第4期42卷 455-455页

作者： Erola Pairo-Castineira Roslin Institute University of Edinburgh Edinburgh UK MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Genomics England London UK Centre for Inflammation Research The Queen’s Medical Research Institute University of Edinburgh Edinburgh UK Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Edinburgh Clinical Research Facility Western General Hospital University of Edinburgh Edinburgh UK Intensive Care National Audit & Research Centre London UK Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia biostatistics Group School of Life Sciences Sun Yat-sen University Guangzhou China The Crick Institute London UK Intensive Care Unit Royal Infirmary of Edinburgh Edinburgh UK School of Life Sciences Westlake University Hangzhou China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou China Wellcome Centre for Human Genetics University of Oxford Oxford UK Department of Medicine University of Cambridge Cambridge UK Department of Intensive Care Medicine Guy’s and St Thomas’ NHS Foundation Trust London UK School of Immunology and Microbial Sciences King’s College London London UK NIHR Health Protection Research Unit for Emerging and Zoonotic Infections Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK MRC-University of Glasgow Centre for Virus Research Institute of Infection Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK Centre for Tropical Medicine and Global Health Nuffield Department of Medicine University of Oxford Oxford UK Clinical Research Centre at St Vincent’s University Hospital Un

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by *** genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC(Genetics Of Mortality In Critical Care)genome-wide association study(GWAS)in 2244 critically ill Covid-19 patients from 208 UK intensive care units(ICUs).We identify and replicate novel genome-wide significant associations,on chr12q24.13(rs10735079,p=1.65[Formula:see text]10-8)in a gene cluster encoding antiviral restriction enzyme activators(OAS1,OAS2,OAS3),on chr19p13.2(rs2109069,p=2.3[Formula:see text]10-12)near the gene encoding tyrosine kinase 2(TYK2),on chr19p13.3(rs2109069,p=3.98[Formula:see text]10-12)within the gene encoding dipeptidyl peptidase 9(DPP9),and on chr21q22.1(rs2236757,p=4.99[Formula:see text]10-8)in the interferon receptor gene *** identify potential targets for repurposing of licensed medications:using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2,and high expression of TYK2,to life-threatening disease;transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe *** results identify robust genetic signals relating to key host antiviral defence mechanisms,and mediators of inflammatory organ damage in *** mechanisms may be amenable to targeted treatment with existing ***-scale randomised clinical trials will be essential before any change to clinical practice.

关键词： lung drugs critical

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