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Impact of pretransplant asplenia vaccination on anti-A/B antibody titers in prospective ABO incompatible kidney transplant recipients

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Rheumatology & Autoimmunity 2023年第1期3卷 26-34页

作者： Elisa Bongetti Mauro S.Sandrin William R.Mulley Department of nephrology Monash HealthClaytonVictoriaAustralia Department of Surgery Austin Health/Northern HealthThe University of MelbourneHeidelbergVictoriaAustralia

Background:Asplenia vaccination is employed before ABO-incompatible(ABOi)transplantation in case splenectomy is *** vaccines have been reported,in different patient groups,to increase anti-A/B titers,through cross-reactivity to shared polysaccharide *** investigated the impact of pretransplant asplenia vaccinations on anti-A/B antibody titers in prospective ABOi renal transplant ***:Published asplenia vaccine microbial structures were reviewed to assess expression of A/B *** patients who underwent ABOi transplantation at Monash Medical centre with anti-A/B titers taken either side of asplenia vaccination were included in a retrospective cohort study between 2007 and *** with paired titers without intervening vaccination were included as *** titers were compared within ***:A and B antigens were found to be expressed by vaccine specific pneumococcal ***-nine ABOi renal transplant recipients received vaccination including at least one pneumococcal *** most common donor to recipient combination was A1 to *** median pre-and postvaccination anti-A/B titers were 1:32 and there was no significant change in titers following vaccination(median change in titer 0 dilutions,range–2 to 3,P=0.43).The same findings were apparent in the control group(n=20).There was no significant change in titer by donor blood group or vaccine *** transplants were canceled or delayed by a rise in anti-A/B titers ***:Pneumococcal vaccination had no clinically relevant impact on anti-A/B titers before ABOi transplantation in this *** results provide reassurance regarding the safety of asplenia vaccination before ABOi transplantation.

关键词： ABO blood-group system asplenia kidney transplantation molecular mimicry splenectomy vaccination

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Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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药物分析学报:英文版 2023年第7期13卷 817-829页

作者： Jiayun Chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu Qiuyan Guo Guangqing Cheng Chen Wang Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ *** on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain *** study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental *** scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during *** could restore neutrophils’chemotaxis and immune function in the septic *** inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during *** also promoted the differentiation and activity of splenic B cells in mice with *** results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the ***,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

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Endoplasmic reticulum stress is involved in podocyte apoptosis induced by saturated fatty acid palmitate

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Chinese Medical Journal 2012年第17期125卷 3137-3142页

作者： TAO Jian-ling WEN Yu-bing SHI Bing-yang ZHANG Hong RUAN Xiong-zhong LI Hang LI Xue-mei DONG Wen-ji LI Xue-wang Division of nephrology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China Institute of Basic Medical Sciences Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China centre for nephrology University College London Medical School London NF3 2PF United Kingdom

Background Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum （ER） stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy. Methods Podocyte apoptosis was detected by 4＇,6-diamidio-2-phenylindole （DAPI） stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 （GRP78）, indicators of ER-associated apoptosis C/EBP homologous protein （CHOP）, and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain. Results Palmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L （10 hours, 13 hours, and 15 hours compared with 0 hour, P 〈0.001） and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours （compared to control, P 〈0.001）. Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control （P 〈0.001）, with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour （P 〈0.001）, with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control. Conclusion Palmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent pro

关键词： diabetic nephropathy endoplasmic reticulum stress free fatty acid podocyte proteinuria

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T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein Ⅰ

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Cellular & Molecular Immunology 2019年第8期16卷 685-693页

作者： David Salem Rebecca Subang Masataka Kuwana Jerrold S.Levine Joyce Rauch Division of Rheumatology Department of MedicineResearch Institute of the McGill University Health CentreMontrealQCCanada Department of Allergy and Rheumatology Nippon Medical SchoolGraduate School of MedicineTokyoJapan Section of nephrology Department of MedicineUniversity of Illinois at ChicagoChicagoILUSA Section of nephrology Department of MedicineJesse Brown Veterans Affairs Medical CenterChicago IL USA

Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in *** to numerous molecularly distinct self-antigens emerge in a sequential manner over several years,leading to disease *** the earliest autoantibodies to appear are those targeting phospholipid-binding proteins,particularlyβ2-glycoprotein Ⅰ.Notably,mice immunized with β2-glycoprotein Ⅰ and lipopolysaccharide develop a strong T cell response to β2-glycoprotein Ⅰ that is associated with autoantibody production and renal disease,similar to that seen in human *** we hypothesized that mice with murine systemic lupus erythematosus,whether induced or spontaneous,should have T cells that recognizeβ2-glycoprotein *** evaluated the response of splenic T cells from mice with induced(C57BL/6 and C3H/HeN)and spontaneous(MRL/lpr)systemic lupus erythematosus to peptides spanning the entire sequence of humanβ*** found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope(peptide 31;LYRDTAVFECLPQHAMFG)in domain Ⅲ ofβ2-glycoprotein I.β2GPI-reactive CD4^(+)T cells from the two models differed primarily in cytokine production:T cells from mice with induced SLE expressed IFN-γ,while T cells from MRL/lpr mice expressed both IL-17 and IFN-γ,indicating that IL-17-expressing T cells are not necessary for generating aβ2GPI-reactive T cell *** data suggest that the generation of aβ2-glycoprotein Ireactive T cell response is shared by both induced and spontaneous models of systemic lupus erythematosus and that this T cell response may mediate epitope spread to autoantibodies in both models.

关键词： β2-glycoprotein I T cells systemic lupus erythematosus autoantibodies MHC class II haplotypes

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Treatment of STING-associated vasculopathy with onset in infancy

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Rheumatology & Autoimmunity 2023年第2期3卷 125-128页

作者： Xiaozhen Zhao Junmei Zhang Caifeng Li Department of Rheumatology Beijing Children's HospitalCapital Medical UniversityNational Centre for Children's HealthBeijingChina Department of nephrology and Rheumatology Children's Hospital Affiliated to Zhengzhou UniversityZhengzhouChina Department of nephrology and Rheumatology Henan Children's Hospital Zhengzhou Children's HospitalZhengzhouChina

To the Editor:Gain-of-function mutations in TMEM173,which encodes the protein stimulator of interferon(IFN)genes(STING),can reportedly cause an autoinflammatory syndrome termed STING-associated vasculopathy with onset in infancy(SAVI).1-3 SAVI is characterized by cutaneous necrotic lesions,growth failure,systemic inflammation,and interstitial lung disease.1,4 Therapeutic management is challenging and difficult:steroids are only partially effective,and patients respond poorly to immunosuppressants.

关键词： interferon inflammation lung

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Lipids-induced Apoptosis Is Aggravated by Acyl-coenzyme A:Cholesterol Acyltransferase Inhibitor

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Chinese Medical Sciences Journal 2010年第2期25卷 76-84页

作者： Jian-ling Tao Xiong-zhong Ruan Hang Li Xue-mei Li Xue-wang Li Department of nephrology Peking Union Medical College Hospital Chinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100730 China centre for nephrology University College London Medical School Royal Free Campus London NW3 2PF UK

Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in endoplasmic reticulum(ER),in order to further understand the mechanism of lipids-induced apoptosis in advanced *** Human vascular smooth muscle cells(VSMCs) and phorbol 12-myristate 13-acetate(PMA) differentiated THP-1 macrophages were *** thymidine incorporation was applied to detect cell *** was assessed by lactate dehydrogenase(LDH) release.4',6-diamidino-2-phenylindole(DAPI) staining,caspase-3,-7 assay,and Annexin-V/propidium iodide(PI) staining were used to detect *** performance liquid chromatography was used in intracellular free cholesterol and cholesterol ester *** free cholesterol was *** Different lipids had different effects on proliferation and cytotoxicity of VSMCs.25-hydroxycholesterol(25OHC) had biphasic effects on the proliferation of *** low concentration,it stimulated cell proliferation,but turned to proliferation inhibition as concentration reached 15 μg/mL.25OHC and acetylated low density lipoprotein(AcLDL) could respectively induce apoptosis in human VSMCs and PMA differentiated THP-1 macrophages,which was aggravated by ACATI,accompanied by increase of intracellular free cholesterol *** was also an increase of cholesterol content in ER with AcLDL-induced apoptosis in THP-1 *** Lipids could induce apoptosis,accompanied by increase of intracellular free cholesterol content,which could be augmented by ACATI,suggesting that insults resulting in ER free cholesterol rise might be the initiator of apoptosis.

关键词：游离胆固醇酰基辅酶A 细胞凋亡诱导凋亡酶抑制剂脂质血管平滑肌细胞 DAPI染色

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Diabetic patients with chronic kidney disease: Non-invasive assessment of cardiovascular risk

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World Journal of Diabetes 2021年第7期12卷 975-996页

作者： Nejc Piko Sebastjan Bevc Robert Ekart Tadej Petreski Nina Vodošek Hojs Radovan Hojs Department of Dialysis Clinic for Internal MedicineUniversity Medical Centre MariborMaribor 2000Slovenia Department of nephrology Clinic for Internal MedicineUniversity Medical Centre MariborMaribor 2000Slovenia Medical Faculty University of MariborMaribor 2000Slovenia

The prevalence and burden of diabetes mellitus and chronic kidney disease on global health and socioeconomic development is already heavy and still *** mellitus by itself is linked to adverse cardiovascular events,and the presence of concomitant chronic kidney disease further amplifies cardiovascular *** culmination of traditional(male gender,smoking,advanced age,obesity,arterial hypertension and dyslipidemia)and non-traditional risk factors(anemia,inflammation,proteinuria,volume overload,mineral metabolism abnormalities,oxidative stress,etc.)contributes to advanced atherosclerosis and increased cardiovascular *** decrease the morbidity and mortality of these patients due to cardiovascular causes,timely and efficient cardiovascular risk assessment is of huge *** risk assessment can be based on laboratory parameters,imaging techniques,arterial stiffness parameters,ankle-brachial index and 24 h blood pressure *** methods include epigenetic markers,soluble adhesion molecules,cytokines and markers of oxidative *** this review,the authors present several non-invasive methods of cardiovascular risk assessment in patients with diabetes mellitus and chronic kidney disease.

关键词： Diabetes mellitus Diabetes complications Chronic kidney disease Atherogenesis Atherosclerosis Cardiovascular risk

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Histological evolution of IgG4 related disease

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Rheumatology & Autoimmunity 2022年第4期2卷 244-246页

作者： Subrahmanian Sathiavageesan Anila Abraham Department of nephrology Sundaram HospitalTrichyTamilnaduIndia Global Clinical Research Scholar Training Harvard Medical SchoolBostonMassachusettsUSA centre for Renal and Urological Pathology ChennaiTamilnaduIndia

To the Editor,IgG4‐related disease(IgG4‐RD)is a multisystem auto‐immune disorder with propensity to involve the *** clinical presentation,1 diagnostic classification criteria 2 and grading of disease activity(Responder Index)3 of IgG4‐RD have been well established,however there is scarce data on histological evolution of this disease entity ensuing immunosuppressive *** is a concern that the dense fibrotic lesions of IgG4‐RD could remain obstinate,notwithstanding immunosuppressive therapy,4 thereby leaving the affected organ with permanent *** present the case of a 57‐year‐old man with multi‐system IgG4‐RD in whom the dense lympho‐plasmocytic intersti-tial inflammation and the typical whorl‐like storiform fibrosis observed in initial kidney biopsy showed a near complete resolution following 4 months of immuno-suppressive therapy.

关键词： IgG4 kidney inflammation

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The Effect of Sacubitril/Valsartan in a Dialysis Patient with Severe Heart Failure*

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Case Reports in Clinical Medicine 2021年第7期10卷 197-202页

作者： Pingping Kong Yanna Dou Xiaoyang Wang Jing Xiao Zhanzheng Zhao The nephrology centre Department of the First Affiliated Hospital of Zhengzhou Zhengzhou China nephrology Institute of Zhengzhou University Zhengzhou China

Heart failure (HF) is a major comorbidity in patients with end-stage renal disease (ESRD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality [1]. The purpose of this report is to describe the efficacy and safety of sacubitril/valsartan for an ESRD patient on hemodialysis therapy conmbined with heart failure with reduced ejection fraction (HFrEF). A 35-year-old woman was undergoing hemodialysis due to ESRD and suffering from heart failure with reduced ejection fraction. Because of worsening heart failure and hypertension, she was prescribed with sacubitril/valsartan at a dose of 50 mg twice a day, spironolactone at a dose of 20 mg three times a day and metoprolol at a dose of 23.75 mg once daily. There was a symptomatic improvement with the heart failure and reduction in NT-proBNP level, accompanied by a decrease of blood pressure after using sacubitric/valsartan. In conclusion, it is safe and effective to take sacubitril/valsartan in this hemodialysis patient with severe heart failure.

关键词： End Stage Renal Disease Sacubitril/Valsartan Hemodialysis Heart Failure Reduced Ejection Fraction

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The Schlager mouse as a model of altered retinal phenotype

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Neural Regeneration Research 2020年第3期15卷 512-518页

作者： Lakshini Y.Herat Aaron L.Magno Márcio G.Kiuchi Kristy L.Jackson Revathy Carnagarin Geoffrey A.Head Markus P.Schlaich Vance B.Matthews Dobney Hypertension centre School of Biomedical Science-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Research centre Royal Perth HospitalPerthAustralia Dobney Hypertension centre School of Medicine-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Neuropharmacology Laboratory Baker Heart and Diabetes InstituteMelbourneAustralia Department of Cardiology and Department of nephrology Royal Perth HospitalPerthAustralia

Hypertension is a risk factor for a large number of vision-threatening eye *** this study,we investigated for the first time the retinal neural structure of the hypertensive BPH/2J mouse(Schlager mouse)and compared it to its control counterpart,the normotensive BPN/3J *** BPH/2J mouse is a selectively inbred mouse strain that develops chronic hypertension due to elevated sympathetic nervous system *** compared to the BPN/3J strain,the hypertensive BPH/2J mice showed a complete loss of outer layers of the neural retina at 21 weeks of age,which was indicative of a severe vision-threatening disease potentially caused by *** elucidate whether the retinal neural phenotype in the BPH/2J strain was attributed to increased BP,we investigated the neural retina of both BPN/3J and BPH/2J mice at 4 weeks of *** preliminary results showed for the first time that the BPH/2J strain develops severe retinal neural damage at a young *** findings suggest that the retinal phenotype in the BPH/2J mouse is possibly due to elevated blood pressure and may be contributed by an early onset spontaneous mutation which is yet to be identified or a congenital defect occurring in this *** characterization of the BPH/2J mouse strain is likely to i)elucidate gene defects underlying retinal disease;ii)understand mechanisms leading to neural retinal disease and iii)permit testing of molecules for translational research to interfere with the progression of retinal *** animal experiments were performed with the approval of the Royal Perth Hospital Animal Ethics Committee(R535/17-18)on June 1,2017.

关键词： blood pressure eye hypertension mice neural regeneration retina Schlager mouse sympathetic nervous system

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