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Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research 2021年第3期9卷 385-395页

作者： Guillaume Courbon Connor Francis Claire Gerber Samantha Neuburg Xueyan Wang Emily Lynch Tamara Isakova Jodie LBabitt Myles Wolf Aline Martin Valentin David Division of Nephrology and Hypertension Department of Medicineand Center for Translational Metabolism and HealthInstitute for Public Health and MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA Nephrology Division Program in Membrane BiologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Division of Nephrology Department of Medicineand Duke Clinical Research InstituteDuke University School of MedicineDurhamNCUSA

Bone-produced fibroblast growth factor 23(FGF23)increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease(CKD).Neutrophil gelatinase-associated lipocalin(NGAL or lipocalin 2;LCN2 the murine homolog)is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD *** investigated bone FGF23 regulation by circulating *** 23 weeks,Col4a3KO mice showed impaired kidney function,increased levels of kidney and serum LCN2,increased bone and serum FGF23,anemia,and left ventricular hypertrophy(LVH).Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum ***2 deletion specifically prevented FGF23 elevations in response to inflammation,but not iron deficiency or phosphate,and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone *** results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in ***2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

关键词： FGF23 kidney inflammation

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Continuous sedation until death:Therapeutically and ethically acceptable

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Journal of Medical Colleges of PLA(China) 2013年第1期28卷 32-34页

作者： MA Ruiqi The Eight-year program on clinical medicine Fudan University

If a patient is dying and still suffering great pain, what is the least harmful alternative? Here we prefer continuous sedation until death (CSD). CSD differs from physician-assisted death (PAD) in many aspects. Firstly, CSD is not used to shorten life or cause death, but instead its intention is to relieve suffering. Secondly, once CSD is associated with a reduction in or suspension of food intake, the duration of sedation is too short to have an impact on survival rate. Thirdly, CSD is titrated while PAD is often overdosed. Fourthly, the sanctity of life could be maintained since sedation is used merely as a means of quelling suffering. Last but no least, for unconscious patients, the same medicines are frequently used for both palliative sedation and standard surgical procedures.

关键词： Deep palliative Medical ethics Medical humanity

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Potassium Dehydroandrographolide Succinate Injection for the Treatment of Child Epidemic Parotitis:A Systematic Review and Meta-Analysis

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Chinese Journal of Integrative medicine 2015年第11期21卷 866-873页

作者：吴嘉瑞张晓朦张冰 Department of clinical Chinese Pharmacy School of Chinese Materia MedicaBeijing University of Chinese Medicine

Objective： To systematically evaluate the clinical efficacy and safety of Potassium Dehydroandrographolide Succinate Injection （PDSI） in the treatment of child epidemic parotitis （EP）. Methods： Randomized controlled trials （RCTs） regarding PDSI in the treatment of child EP were searched in China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from inception to July 30, 2013. Two reviewers independently retrieved RCTs and extracted information. The Cochrane risk of bias method was used to assess the quality of included studies, and a meta- analysis was conducted with RevMan 5.2 software. Results： A total of 11 studies with 818 participants were included. The quality of the studies was generally low, among which only one study mentioned the random method. The meta-analysis indicated that PDSI was more effective than the conventional therapy with Western medicine for EP in the outcomes of the total effective rate [relative risk （RR）=1.23, 95% confidence interval （CI） [1.14, 1.33], P〈0.01], the time of temperature return to normal, the time of detumescence [mean difference （MD）=-2.10, 95% CI [-2.78, -1.41], P〈0.01], and the incidence of complications （RR=0.14, 95% CI [0.03, 0.72], P=0.02）. There were 6 adverse drug reactions （ADRs） in this systematic review, 2 of which were mainly represented rash and diarrhea in the experiment group, while another 4 ADRs occurred in the control group. Conclusions： Based on the systematic review, PDSI was effectiveness and relatively safety in the treatment of child EP. But further rigorously designed trials are warranted to determine its effectiveness.

关键词： Potassium Dehydroandrographolide Succinate Injection child epidemic parotitis meta-analysis systematic review Chinese medicine

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Epidemiological and clinical Features of Rotavirus and Adenovirus Related Gastroenteritis in Beijing:A Retrospective Case-control Study in Pediatric Patients

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Biomedical and Environmental Sciences 2020年第3期33卷 196-200页

作者： DONG Jing Xiao LI Ao Fei LI Run Qing CHAO Shuang YANG Song ZHAO Xiu Ying Department of clinical Laboratory Beijing Tsinghua ChangGung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China School of medicine Tsinghua UniversityBeijing 100084China

Rotavirus(RV)is the most common cause of viral gastroenteritis among children younger than 5-yearold *** has nine groups(Group A to I)and Group A(RVA)is the main cause of severe gastroenteritis disease in *** adenovirus(HAdV)consists of 7 species(HAdV-A through HAdV-G)including over 70 serotypes,and group F serotypes 40 and 41 are related to gastroenteritis[1].There were reports that revealed co-infection of AdV with RVA and Norovirus[2].Here we report an epidemiological and clinical analysis of RVA and AdV infection through a single-centered retrospective case-control study.

关键词： Rotavirus(RV) viral gastroenteritis children

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The transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines

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Asian Journal of Andrology 2019年第5期21卷 460-467页

作者： Octavio Orellana-Serradell Daniela Herrera Enrique A Castellon Hector R Contreras Department of Basic and clinical Oncology Faculty of MedicineUniversity of ChileIndependenciaSantiago 8380453Chile

One of the factors promoting tumoral progress is the abnormal activation of the epithelial-mesenchymal transition(EMT)program which has been associated with chemoresistance in tumoral *** transcription factor zinc finger E-box-binding homeobox 1(ZEB1),a key EMT activator,has recently been related to docetaxel resistance,the main chemotherapeutic used in advanced prostate cancer *** mechanisms involved in this protective effect are still *** a previous work,we demonstrated that ZEB1 expression induced an EMT-like phenotype in prostate cancer cell *** this work,we used prostate cancer cell lines 22Rvl and DU145 to study the effect of ZEB1 modulation on docetaxel resistance and its possible *** results showed that ZEB1 overexpression conferred to 22Rvl cell resistance to docetaxel while its silencing made DU145 cells more sensitive to *** of resistance markers showed no presenee of ATP-binding cassette subfamily B member 1(MDR1)and no changes in breast cancer resistance protein(BCRP)or ATP-binding cassette subfamily C member 10(MRP7).However,a correlation between ZEB1,multidrug resistance-associated protein 1(MRP1),and ATP-binding cassette subfamily C member 4(MRP4)expression was ***4 inhibition,using MK571,resensitized cells with ZEB1 overexpression to docetaxel *** addition,modulation of ZEB1 and subsequent change in MRP4 expression correlated with a lower apoptotic response to docetaxel,characterized by lower B-cell lymphoma 2(Bcl2),high BCL2-associated X protein(Bax),and high active caspase 3 *** response to docetaxel in our model seems to be mediated mainly by activation of the apoptotic death *** results showed that modulation of MRP4 could be a mediator of ZEBl-related resistance to docetaxel in prostate cancer,making it a possible marker for chemotherapy response in patients who do not express MDR1.

关键词： chemoresistance prostate cancer ZEB1

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Neuropeptide Y and leptin receptor expression in the hypothalamus of rats with chronic immobilization stress

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Neural Regeneration Research 2013年第18期8卷 1721-1726页

作者： Shaoxian Wang Jiaxu Chen Guangxin Yue Minghua Bai Meijing Kou Zhongye Jin School of Pre-clinical medicine Beijing University of Chinese Medicine Traditional Chinese medicine College of Hebei Medical University Institute of Basic Theory in Chinese medicine China Academy of Chinese Medical Sciences

In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.

关键词： neural regeneration chronic immobilization stress hypothalamus arcuate nucleus doubleimmunofluorescence neuropeptide Y leptin receptor feeding center body weight grants-supported paper neuroregeneration

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Efficacy and safety of puerarin injection in treatment of diabetic peripheral neuropathy: a systematic review and Meta-analysis of randomized controlled trials

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Journal of Traditional Chinese medicine 2014年第4期34卷 401-410页

作者： Jiarui Wu Xiaomeng Zhang Bing Zhang Department of clinical Chinese Pharmacy School of Chinese Materia Medica Beijing University of Chinese Medicine

OBJECTIVE: To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of diabeticperi pheral neuropathy(DPN).METHODS: Randomized controlled trials investigating the efficacy of puerarin injection on DPN were searched for in China National Knowledge Infrastructure Database, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from establishment to April *** reviewers independently retrieved and extracted the *** included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.2 ***: Twenty-two studies involving 1664 participants were included. The quality of the studies was found to be relatively low. Meta-analysis showed that puerarin injection combined with western medication was more effective than conventional therapy for rate, nerve conduction velocity(NCV), and hemorheology index. Six adverse drug reactions(ADRs) from puerarin injection were reported in two studies. Reactions included facial flushing, palpitations, and pain at infusion locations. However,noserious ADRs were ***: Puerarin injection was effective for the treatment of DPN. Puerarin can improve the total effective rate, correct NCV that was decreased by diabetes, and improve the hemorheology *** was also relatively safe clinically. However,since the articles included in the study were not high-quality, more studies should be conducted to strengthen their findings.

关键词： Puerarin Diabetic neuropathies Treatment outcome Meta-analysis Randomized controlledtrials

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Most patients with non-hypertensive diseases at a critical care resuscitation unit require arterial pressure monitoring: a prospective observational study

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World Journal of Emergency medicine 2023年第3期14卷 173-178页

作者： Emily Engelbrecht-Wiggans Jamie Palmer Grace Hollis Fernando Albelo Afrah Ali Emily Hart Dominique Gelmann Iana Sahadzic James Gerding Quincy K.Tran Daniel J.Haase University of Maryland School of medicine Baltimore 21201USA The Research Associate program in Emergency medicine and Critical Care Department of Emergency MedicineUniversity of Maryland School of MedicineBaltimore 21201USA Department of Emergency medicine University of Maryland School of MedicineBaltimore 21201USA program in Trauma the R Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimore 21201USA

BACKGROUND:Blood pressure(BP)monitoring is essential for patient *** arterial BP(IABP)is more accurate than non-invasive BP(NIBP),although the clinical signifi cance of this diff erence is *** hypothesized that IABP would result in a change of management(COM)among patients with non-hypertensive diseases in the acute phase of ***:This prospective study included adults admitted to the Critical Care Resuscitation Unit(CCRU)with non-hypertensive disease from February 1,2019,to May 31,*** plans to maintain a mean arterial pressure>65 mmHg(1 mmHg=0.133 kPa)were recorded in real time for both NIBP and IABP measurements.A COM was defined as a discrepancy between IABP and NIBP that resulted in an increase/decrease or addition/discontinuation of a medication/*** and regression tree analysis identified significant variables associated with a COM and assigned relative variable importance(RVI)***:Among the 206 patients analyzed,a COM occurred in 94(45.6%[94/206])*** most common COM was an increase in current infusion dosages(40 patients,19.4%).Patients receiving norepinephrine at arterial cannulation were more likely to have a COM compared with those without(45[47.9%]vs.32[28.6%],P=0.004).Receiving norepinephrine(relative variable importance[RVI]100%)was the most signifi cant factor associated with a *** complications were identifi ed with IABP ***:A COM occurred in 94(45.6%)non-hypertensive patients in the *** vasopressors was the greatest factor associated with *** should consider IABP monitoring more often in non-hypertensive patients requiring norepinephrine in the acute resuscitation *** studies are necessary to confi rm the risk-to-benefi t ratios of IABP among these high-risk patients.

关键词： Non-hypertensive diseases Invasive arterial blood pressure Non-invasive blood pressure

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SynergyFinder Plus:Toward Better Interpretation and Annotation of Drug Combination Screening Datasets

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 587-596页

作者： Shuyu Zheng Wenyu Wang Jehad Aldahdooh Alina Malyutina Tolou Shadbahr Ziaurrehman Tanoli Alberto Pessia Jing Tang Research program in Systems Oncology Faculty of MedicineUniversity of HelsinkiHelsinki 00290Finland

Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The Synergy Finder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the Synergy Finder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated Synergy Finder R package includes five main innovations. 1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. 2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. 3)We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. 4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. 5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.s *** as a user-friendly interface to enable a more fexible and versatile analysis of drug combination data.

关键词： SynergyFinder Drug combination Synergy modeling Drug discovery Drug combination sensitivity analysis

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Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells

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World Journal of Gastroenterology 2005年第8期11卷 1122-1130页

作者： Elisabetta Ceni Tommaso Mello Mirko Tarocchi David W Crabb Anna Caldini Pietro Invernizzi Calogero Surrenti Stefano Milani Andrea Galli Gastroenterology Unit Farmacogenomic Foundation FioiGen Departments of medicine and of Biochemistry and Molecular Biology clinical Chemistry Laboratories Department of medicine Ospedale San Paolo

AIM: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of same epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferator-activated receptor γ (PPARγ), the mechanism by which TZD exert their anticancer effect is presently unclear. In this study, we analyzed the mechanism by which TZD inhibit growth of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma. METHODS: The effects of TZD in pancreatic cancer cells were assessed in anchorage-independent growth assay. Expression of PPARy was measured by reverse-transcription polymerase chain reaction and confirmed by Western blot analysis. PPARy activity was evaluated by transient reporter gene assay. Flow cytometry and DMA fragmentation,assay were used to determine the effect of TZD on cell cycle progression and apoptosis respectively. The effect of TZD on ductal differentiation markers was performed by Western blot. RESULTS: Exposure to TZD inhibited colony formation in a PPARγ-dependent manner. Growth inhibition was linked to G1 phase cell cycle arrest through induction of the ductal differentiation program without any increase of the apoptotic rate. CONCLUSION: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth by a PPAR-dependent induction of pacreatic ductal differentiation.

关键词： Thiazolidinediones Pancreatic cancer PPARγ Cancer growth Differentiation

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