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Molecular basis of ataxia telangiectasia and related diseases

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Acta Pharmacologica Sinica 2005年第8期26卷 897-907页

作者： Lindsay g Ball Department of Microbiotogy and Lmmunology University of Saskatchewan S7n 5E5 SK Canada Saskatoon

Ataxia telangiectasia (AT) is a rare human disease characterized by extreme cellular sensitivity to radiation and a predisposition to cancer, with a hallmark of onset in early childhood. Several human diseases also share similar symptoms with AT albeit with different degrees of severity and different associated disorders. While all AT patients contain mutations in the AT-mutated gene (ATM), most other AT-like disorders are defective in genes encoding an MRN protein complex consisting of Mre11, Rad50 and Nbs1. Both ATM and MRN function as cellular sensors to DNA double-strand breaks, which lead to the recruitment and phosphorylation of an array of substrate proteins involved in DNA repair, apoptosis and cell-cycle cbeckpoints, as well as gene regulation, translation initiation and telomere maintenance. ATM is a member of the family of phosphatidylinositol 3-kinase-like protein kinases (PIKK), and the discovery of many ATM substrates provides the underlying mechanisms of heterologous symptoms among AT patients. This review article focuses on recent findings related to the initial recognition of double-strand breaks by ATM and MRN, as well as a DNA-dependent protein kinase complex consisting of the heterodimer Ku70/Ku80 and its catalytic subunit DNA-PKcs, another member of PIKK. This possible interaction suggests that a much greater complex is involved in sensing, transducing and co-ordinating cellular events in response to genome instability.

关键词： ataxia telangiectasia DNA damage DNA repair cdc genes phosphotransferases

Crescentic glomerulonephritis in children:a single centre experience

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世界儿科杂志:英文版 2016年第2期12卷 225-230页

作者： Sare gülfemÖzlü AysunÇaltık Özlem Aydoğ Mehmet Bülbül gülay Demircin EvrimÇakıcı Nilüfer Arda AyşeÖner Department of Pediatric Nephrology Dr Sami Ulus Childrens and Maternity HospitalAnkaraTurkey Department of Pathology Sami Ulus Childrens and Maternity HospitalAnkaraTurkey

Background:Crescentic glomerulonephritis(CsgN)is characterized by crescents in 50%or more of glomeruli and clinically by a sudden and progressive decline in renal ***:We evaluated the etiology,clinical features,prognostic factors and long-term outcome of *** January 2000 and December 2010,45 children(26 girls,19 boys)with biopsy-proven CsgN(>50%crescents)were investigated ***:The mean age of the patients was 130.86±33.77 *** mean duration of symptoms prior to diagnosis was 26±12 days(4-40 days).Most of the children had hypertension(62.2%),macroscopic hematuria(73.3%),oligoanuria(44.4%),edema(51.1%)and purpuric rash(40%)at *** final clinical status of the patients was complete remission(n=21),partial remission(n=5)or chronic kidney disease(n=19).Adverse outcomes were significantly associated with a long duration between the onset of symptoms and treatment(P=0.038),the presence of oligoanuria(P=0.006),a severe decreased glomerular filtration rate(gFR75%)(P=0.03),and the ratio of fi brous crescents(P=0.015).Conclusion:The outcome of CsgN in children continues to be poor,and it should be treated as a renal emergency.

关键词： glomerulonephritis renal biopsy renal failure

Updates in immunotherapy for hepatocellular carcinoma

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Hepatoma Research 2019年第10期5卷 19-31页

作者： Leonardo g.da Fonseca Flair JoséCarrilho Medical Oncology São Paulo Clínicas Liver Cancer GroupHospital das Clínicas ComplexInstituto do Cancer do Estado de São PauloUniversity of São Paulo School of MedicineSão PauloSP 05403-000Brazil Department of gastroenterology São Paulo Clínicas Liver Cancer GroupHospital das Clínicas ComplexInstituto do Cancer do Estado de São PauloUniversity of São Paulo School of MedicineSão PauloSP 05403-000Brazil

Hepatocellular carcinoma(HCC)carries an unfavorable prognosis and novel therapeutic strategies are *** now,only few systemic agents have improved survival in patients with advanced stage *** changed the landscape in several tumor types by producing unprecedented clinical outcomes with a favorable safety *** presents a particular immune-suppressive microenvironment and HCC develops in a background of chronic inflammation in the vast majority of *** this regard,immunotherapy may be a suitable *** research focused on therapies involving immune cells and anti-tumor immune response for HCC has shown encouraging preliminary *** checkpoint inhibitors,such the anti-PD-1/PD-L1 monoclonal antibodies,have provided durable responses in patients with advanced stage disease,although the pioneers phaseⅢtrials did not confirm survival superiority over the available *** vaccines,adoptive cellular therapies and combinations of local modalities with immunotherapy are promising approaches under active research.

关键词： Hepatocellular carcinoma immunotherapy immunosuppression prognosis immunology antibody vaccine

Drug-eluting stents: is it the beginning of the end for coronary artery bypass surgery?

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Chinese Medical Journal 2004年第9期117卷 1377-1387页

作者： Shahzad g Raja Department of Cardiac Surgery Royal Hospital for Sick Children Yorkhill NHS TrustGlasgow G3 8SJScotland

Myocardial revascularization therapy of coronary artery disease is one of the most important medical advances of the past 50 years. Coronary revascularization by either bypass surgery or coronary angioplasty relieves angina and may improve the prognosis in patients with coronary artery disease. Randomized comparisons reveal no difference in survival free from myocardial infarction (MI ) between surgery and balloon angioplasty. Stenting significantly improved the long-term outcome, while surgery is still associated with fewer reinterventions during follow-up. However, subsequent improvements in both percutaneous and surgical techniques may now limit the validity of any conclusions that have been drawn from the earlier studies. In fact, the lines of demarcation for patients suited for bypass or angioplasty are becoming blurry with each passing day.

关键词： coronary arteriosclerosis · percutaneous coronary interventions · drug-eluting stents

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Corrosion and cavitation erosion resistance enhancement of cast Ni–Al bronze by laser surface melting

作者： (英)亚当·斯密(adam Smith)

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Journal of Iron and Steel Research International 2022年第2期29卷 359-369页

作者： Q.N.Song Y.Tong H.L.Li H.N.Zhang N.Xu g.Y.Zhang Y.F.Bao W.Liu Z.g.Liu Y.X.Qiao Engineering Research Center of Dredging Technology of Ministry of Education Hohai UniversityChangzhou213022JiangsuChina College of Mechanical and Electrical Engineering Hohai UniversityChangzhou213022JiangsuChina College of Materials Science and Engineering Jiangsu University of Science and TechnologyZhenjiang212003JiangsuChina

Laser surface melting (LSM) was applied on a cast Ni–Al bronze (NAB), which was a crucial material for marine ship propellers. A 720 μm-thick LSM layer with fine equiaxed and dendritic microstructures was obtained. After immersion for 30 days, the corrosion rate of cast NAB was reduced by 25% after LSM. Preferential corrosion occurred and deep corrosion pits appeared at α + κIII microstructure for the cast NAB. LSM NAB underwent general corrosion, and a much more protective film formed on the surface because of the homogenized microstructure. The mass loss of the cast NAB was approximately 2.1 times larger than that of LSM NAB after cavitation erosion (CE) in 3.5 wt.% NaCl solution for 5 h. For the two materials, the mechanical impact effect was dominantly responsible for CE damage. Therefore, the improved hardness and homogenized microstructure contributed to the improved CE resistance of LSM NAB. CE destructed the film, shifted the open circuit potential toward a more negative value, and raised the current density by an order of magnitude. Corrosion at the cast eutectoid microstructure and the dendrites of LSM NAB facilitates the degradation under the cavitation attack. CE-corrosion synergy was largely caused by corrosion-enhanced-CE.

关键词： Laser surface melting Ni-Al bronze Microstructure Corrosion Cavitation erosion Synergy

Rationale for creation of capillary breaking layers in cold regions subgrade by pressure injection of waterproofing compounds

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Research in Cold and Arid Regions 2021年第5期13卷 366-371页

作者： D.A.Razuvaev A.L.Lanis M.g.Chakhlov Siberian Transport University Dusi Koval'chuk Street191Novosibirsk 630049Russian

In the presents work,the authors have carried out a field study of moisture transfer processes in highway subgrades in a cold region during freezing and laboratory experiments on freezing samples of silicified soils used as a capillary *** study showed that the creation of a capillary barrier from an injected solution,blocking the access of groundwater to the freezing zone,will reduce the amount of heaving to permissible *** on the results of laboratory studies,an exponential dependence of the relative deformation due to frost heaving on the relative height of soil silicatization in the freezing zone has been *** creating a capillary barrier in the already existing subgrade,the authors have proposed designs of injection-silicified soils and substantiated the use of such soils.

关键词： capillary barrier subgrade soil injection silicified soil cold regions

The evolution of lower extremity reconstruction

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Plastic and Aesthetic Research 2022年第1期9卷 182-195页

作者： Brogan g.A.Evans David L.Colen Division of Plastic and Reconstructive Surgery Department of SurgeryYale School of MedicineNew HavenCT 06510USA

Reconstruction of the lower extremity is a complex task that has evolved greatly in both technique and indication over the past *** advances in treating traumatic lower extremity injuries focused on primary amputation to avoid the high mortality of *** introduction of antibiotics improved surgical debridement and local reconstructive options,enhancing the viability of lower extremities with simple and proximal *** the advent of microvascular surgery,free tissue transfer techniques provided a means to reconstruct more distal and complex *** these surgical techniques have continued to evolve,so too have indications for reconstruction,patient management and post-operative care-now with a greater emphasis on patient quality of life and limb *** purpose of this article is to outline the evolution of lower extremity reconstruction,and how the standard of practice has changed over time.

关键词： Lower extremity lower extremity reconstruction limb salvage free flap perforator flap vascularized bone flap orthoplastic surgery

Chromophobe renal cell carcinoma: Novel molecular insights and clinicopathologic updates

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Asian Journal of Urology 2022年第1期9卷 1-11页

作者： Reza Alaghehbandan g.Przybycin Christopher Virginie Verkarre Rohit Mehra Department of Pathology Faculty of MedicineUniversity of British ColumbiaRoyal Columbian HospitalVancouverBCCanada Robert J Tomsich Pathology and Laboratory Medicine Institute Cleveland ClinicClevelandOHUSA Department of Pathology Georges Pompidou European HospitalAP-HPParis UniversityINSERM UMR 970PARCCParisFrance Department of Pathology University of Michigan Medical SchoolAnn ArborMIUSA Michigan Center for Translational Pathology Ann ArborMIUSA Rogel Cancer Center Michigan MedicineAnn ArborMIUSA

Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic *** are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and *** ChRCCs carry a favorable clinical *** alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid *** with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ***53 and PTEN are the two most frequently mutated genes in *** major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic *** eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene ***,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.

关键词： Renal cell carcinoma Chromophobe Immunohisto-chemistry RNA in situ hybridization Next-generation sequencing Oncocytic tumors Molecular