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Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

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World journal of Gastroenterology 2008年第1期14卷 38-45页

作者： Yvonne meier Tina Zodan Carmen Lang Roland Zimmermann Gerd A Kullak-Ublick peter j meier Bruno Stieger Christiane Pauli-Magnus Division of Clinical Pharmacology and Toxicology Department of Internal Medicine University Hospital Zurich Zurich Switzerland Department of Gynecology and Obstetrics University Hospital Zurich Zurich Switzerland Division of Clinical Pharmacology and Toxicology Department of Internal Medicine University Hospital Zurich Zurich Switzerland Clinical Trial Unit University Hospital Basel Basel Switzerland

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

关键词： Cholestasis of pregnancy Contraceptive-induced cholestasis Bile salt export pump Multidrugresistance associated protein 2 Pharmacogenetics

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Hepatocellular transport proteins and their role in liver disease

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World journal of Gastroenterology 2001年第2期7卷 157-169页

作者： Carmen Stanca Diana jung peter j.meier Gerd A.Kullak-Ublick Division of Gastroenterology and Hepatology and Division of Clinical Pharmacology and Toxicology Department of Internal MedicineUniversity HospitalCH-8091 Zurich/Switzerland

MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte... 详细信息

关键词： ATP-Binding Cassette Transporters Animals Carrier Proteins Hepatocytes Humans Liver Liver Diseases Organic Anion Transporters Organic Cation Transport Proteins Research Support, Non-U.S. Gov't

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Comparison of methods for deriving phenotypes from incomplete observation data with an application to age at puberty in dairy cattle

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journal of Animal Science and Biotechnology 2024年第2期15卷 535-545页

作者： Melissa A.Stephen Chris R.Burke jennie E.Pryce Nicole M.Steele peter R.Amer Susanne meier Claire V.C.Phyn Dorian j.Garrick DairyNZ Ltd 605 Ruakura RoadHamilton 3240New Zealand AL Rae Centre for Genetics and Breeding-Massey University RuakuraHamilton 3214New Zealand Agriculture Victoria Research AgriBioCentre for AgriBioscienceBundooraVictoria 3083Australia School of Applied Systems Biology La Trobe UniversityBundooraVictoria 3083Australia AbacusBio DunedinNew Zealand

Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure *** include time-dependent traits such as reproductive status,or *** measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound *** we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AGEP4),which generally coincides with onset of puberty,as an example *** We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New *** used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three *** methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation *** Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was *** sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to *** estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring *** Our results indicate that using

关键词： Cattle Gibbs sampler Markov-chain Monte Carlo(MCMC) Puberty

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THE EFFECTS OF TWELVE WEEKS OF TAI CHI PRACTICE ON ANXIETY IN STRESSED BUT HEALTHY PEOPLE COMPARED TO EXERCISE AND WAIT-LIST GROUPS:A RANDOMISED CONTROLLED TRIAL

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journal of Integrative Medicine 2014年第3期 297-298页

作者： Shuai Zheng Sara Lal peter meier David Sibbritt Chris Zaslawski University of Technology

Introduction: The ancient Chinese mind-body exercise of Tai Chi(TC) is practiced worldwide by millions of people *** has been a growing interest in the scientific community to evaluate the efficacy of TC practice for a range of diseases and ***: Forty-nine participants were randomly allocated into one of three groups: TC(n=17), exercise(n=16) or a wait-list control group(WL)(n=16).Both TC and exercise groups were required to complete 5 h per week of either TC or exercise for 12 weeks(total of 3600 min), whilst WL maintained their normal *** Trait Anxiety Inventory(STAI) which assesses both state anxiety(Y-1) and trait anxiety(Y-2) was used as the primary outcome *** outcome measures werethe Perceived Stress Scale 14(PSS14), blood pressure, heart rate variability, visual analogue scale and short-form *** were collected at baseline, midway at week 6 and at the completion of the trial at week 12.A two-way ANOVA with repeated measures followed by Bonferroni's post-hoc test was used for statistical ***: For the Y-1 outcome measure both TC and exercise groups showed significant improvements from baseline to week 12(P<0.01).Significant improvements from baseline were also seen for both TC and exercise groups at weeks 6 and 12 in both the Y-2(P<0.01) and PSS14(P<0.01) outcome *** analysis detected statistical significance between TC and WL at week 12 for both Y-1(P<0.01) and Y-2(P<0.01) outcome measures but not for PSS14 ***: The findings from this clinical study revealed that TC effectively reduces stress levels in healthy individuals as early as week 6 and may provide a gentler therapeutic alternative to strenuous exercise.

关键词： TC PSS

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动态绩效管理:实时价值优化的力量

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经理人 2021年第1期 74-75页

作者： peter Smith Philip meier L.E.K.咨询公司

企业管理人员都希望把注意力集中在有意义的决策上,因此他们更加看重和需要关键绩效指标(KPI)的实时信息。本文提出的三步走流程:创建价值模型;深入整合KPI;实时价值优化,将为企业提供创建实时价值优化的解决方案,帮助企业实现高层次收益。

关键词：企业管理人员价值模型动态绩效实时信息价值优化注意力集中三步走解决方案

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Coronary heart disease incidence and competing risks： an important issue

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journal of Geriatric Cardiology 2017年第7期14卷 425-429页

作者： Paolo Emilio Puddu peter Louis Amaduzzi Beatrice Ricci Department of Cardiovascular Respiratory Nephrological Anesthesiological and Geriatric Sciences Sapienza University of Rome italy Department of Experimental Diagnostics and Specialty Medicine Univerity of Bologna Italy

The estimation of lifetime morbid events is not a rare presentation of relatively old and of more recent epidemi- ological investigations, accompanied by evaluating rates, risks and predictors （more in general determinants or risk factors）. However, when the follow-up period is very long and Kaplan-meier survival curves are adopted, or Kaplan- meier-based more complex models such as Cox＇s analysis are used, clinical （or epidemiological） reality may well be distorted since by these survival methods risks tend to be overestimated, whereas survival tends to be reduced.

关键词： Coronary heart disease Competing risks The elderly

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Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma:results from a retrospective multicenter trial

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Frontiers of Medicine 2023年第5期17卷 878-888页

作者： Elias A.T.Koch Anne Petzold Anja Wessely Edgar Dippel Markus Eckstein Anja Gesierich Ralf Gutzmer jessica C.Hassel Harald Knorr Nicole Kreuzberg Ulrike Leiter Carmen Loquai Friedegund meier Markus Meissner peter Mohr Claudia Pföhler Farnaz Rahimi Dirk Schadendorf Max Schlaak Kai-Martin Thoms Selma Ugurel jochen Utikal Michael Weichenthal Beatrice Schuler-Thurner Carola Berking Markus V.Heppt Department of Dermatology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Comprehensive Cancer Center Erlangen—European Metropolitan Area of Nürnberg(CCC ER-EMN) 91054ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Bavarian Cancer Research Center(BZKF) Uniklinikum ErlangenÖstliche Stadtmauerstraße 3091054ErlangenGermany Department of Dermatology Ludwigshafen Medical Center67059LudwigshafenGermany Institute of Pathology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg91054ErlangenGermany Department of Dermatology University Hospital Würzburg97080WürzburgGermany Skin Cancer Center Minden Department of DermatologyMühlenkreiskliniken AöRRuhr UniversityBochum Campus Minden32423MindenGermany Skin Cancer Center Department of Dermatology and National Center for Tumor Diseases(NCT)University Hospital Heidelberg69120HeidelbergGermany Department of Ophthalmology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Department of Dermatology and Venereology Skin Cancer Center at the Center of Integrated Oncology(CIO)Köln BonnUniversity Hospital of Cologne50937CologneGermany Department of Dermatology Center for DermatooncologyUniversity Hospital Tübingen72056TübingenGermany Department of Dermatology University Medical Center Mainz55131MainzGermany Skin Cancer Center at the University Cancer Center Dresden and National Center for Tumor Diseases&Department of Dermatology University Hospital Carl Gustav Carus01307DresdenGermany Department of Dermatology Venereology and AllergologyGoethe University60590Frankfurt am MainGermany Department of Dermatology Elbeklinikum21614BuxtehudeGermany Department of Dermatology Saarland University Medical School66421Homburg/SaarGermany Department of Dermatology and Allergy Munich University Hospital(LMU)81377MunichGermany Departmen

Metastases of uveal melanoma(UM)spread predominantly to the *** to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor *** impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this *** were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort *** data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词： uveal melanoma liver-directed therapy immune checkpoint blockade SIRT anti-PD-1 anti-CTLA-4

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Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study

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World journal of Gastrointestinal Oncology 2020年第5期12卷 549-558页

作者： peter H Cashin Lana Ghanipour Malin Enblad David L Morris Department of Surgical Sciences Section of SurgeryUppsala UniversityAkademiska SjukhusetUppsala 75185Sweden Department of Surgery University of New South WalesSydney 2217New South WalesAustralia

BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(HIPEC)treatment have never been *** To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free *** All patients with colorectal peritoneal metastases(1996-2015)completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a biinstitutional database(Uppsala and Sydney)were included in the ***-Dindo grade 3-4 morbidity differences between the neutropenia group vs nonneutropenia group were calculated and Kaplan-meier curves with log rank test were *** and multivariable Cox regression models for diseasefree survival were *** Two hundred and forty-six patients were identified–32 postoperative any-grade neutropenia patients and 214 non-neutropenia *** neutropenia group had more combination oxaliplatin+irinotecan treatment than the nonneutropenia group(66%vs 13%,P=0.0001).The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 *** overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group,P=*** disease-free survival was 16 mo vs 11 mo,respectively,P=*** was an independent prognostic factor for disease-free survival with hazard ratio:0.58,95%confidence interval:0.36-0.95,P=*** 13%of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 *** was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC *** is in direct contrast to the current paradigm of decreasing the treatment intensity.

关键词： Colorectal cancer Peritoneal metastases Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Oxaliplatin Neutropenia

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西德乌拉赫Ⅲ号干热岩探井的钻井和完井工艺

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国外地质勘探技术 1984年第1期 25-29页

作者： Udo meier D.I.peter L.Ernst 郭文芝

一、前言乌拉赫地热异常区位于德意志联邦共和国的西南部,距斯图加特市40公里。该地区是比较年轻的火山活动区域,总面积约为80平方公里。乌拉赫地区的热异常大约在150年前就已发现。现在生产的热水都来自侏罗纪和三迭纪岩层,主要用于医... 详细信息

一、前言乌拉赫地热异常区位于德意志联邦共和国的西南部,距斯图加特市40公里。该地区是比较年轻的火山活动区域,总面积约为80平方公里。乌拉赫地区的热异常大约在150年前就已发现。现在生产的热水都来自侏罗纪和三迭纪岩层,主要用于医疗,也有一部分用于

关键词：岩心地热异常区岩芯拉赫取心钻头干热岩取心管岩层结晶基底地台基底钻井

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Treatment trends of muscle invasive bladder cancer: Evidence from the Surveillance, Epidemiology, and End Results database, 1988 to 2013

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Asian journal of Urology 2023年第1期10卷 9-18页

作者： Victor Chalfant Michael L.Blute jr peter Silberstein Urology at CHI Health Creighton University Medical Center Omaha NEUSA Hematology Oncology at CHI Health Creighton University Medical Center Omaha NEUSA

Objective:Guidelines for muscle-invasive bladder cancer(MIBC)recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy *** trends and practice patterns of MIBC have been defined using the National Cancer Database,data using the Surveillance,Epidemiology,and End Results(SEER)program have been poorly ***:Using the SEER database,we collected data of MIBC according to the American joint Commission on *** considered differences in patient demographics and tumor charac-teristics based on three treatment groups:chemotherapy(both adjuvant and neoadjuvant)with radical cystectomy,radical cystectomy,and *** logistic regression was performed to compare likelihood *** trends were included for each treatment ***-meier curves were performed to compare cause-specific sur-vival.A Cox proportional-hazards model was utilized to describe predictors of ***:Of 16728 patients,10468 patients received radical cystectomy alone,3236 received chemotherapy with radical cystectomy,and 3024 received *** who received chemoradiotherapy over radical cystectomy were older and more likely to be African American;stage III patients tended to be *** who received chemotherapy with radical cystectomy tended to be males;stage II patients were less likely to be Asian than *** III patients were less likely to receive chemoradiotherapy as a treatment op-tion than stage *** with radical cystectomy and chemoradiotherapy are both un-derutilized treatment options,though increasingly ***-meier survival curves showed significant differences between stage II and III tumors at each interval.A Cox proportional-hazards model showed differences in gender,tumor stage,treatment modality,age,andmarital ***:Radical cystectomy alone is still the most commonly used treatment for muscle-invasive

关键词： Muscle-invasive bladdercancer Bladder-preservation therapy Chemoradiotherapy Transurethral resectionof bladder tumor Surveillance Epidemiology,and EndResultsProgram Patient demographics Practicetrends Kaplan-meier survival curves

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