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Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu Huiyan Wang Chenyan Dai Haixiang Sun Jianwu Dai Yali Hu department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China department of Hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive *** we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so *** verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical *** 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January *** per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control *** ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)*** group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic *** incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were *** conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate

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Expert consensus on the diagnosis and therapy of endo-periodontal lesions

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International Journal of Oral Science 2024年第3期16卷 381-389页

作者： Bin Chen Yanan Zhu Minkui Lin Yangheng Zhang Yanfen Li Xiangying Ouyang Song Ge Jiang Lin Yaping Pan Yan Xu Yi Ding Shaohua Ge Faming Chen Zhongchen Song Shaoyun Jiang Jiang Sun Lijun Luo Junqi Ling Zhi Chen Lin Yue Xuedong Zhou Fuhua Yan department of Periodontology Nanjing Stomatological HospitalAffiliated Hospital of Medical SchoolInstitute of StomatologyNanjing UniversityNanjingChina department of Endodontics Nanjing Stomatological HospitalAffiliated Hospital of Medical SchoolInstitute of StomatologyNanjing UniversityNanjingChina Clinical Research center for Oral Tissue Deficiency Diseases of Fujian Province&Fujian Key Laboratory of Oral Diseases&Fujian Provincial Engineering Research center of Oral Biomaterial School and Hospital of StomatologyFujian Medical UniversityFuzhouChina department of Periodontology Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina School and hospital of Stomatology Zunyi Medical UniversityZunyiChina department of Stomatology Beijing TongRen HospitalCapital Medical UniversityBeijingChina department of Periodontics School and Hospital of StomatologyChina Medical UniversityShenyangChina department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityJiangsu Key Laboratory of Oral DiseasesNanjing Medical UniversityNanjingChina State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical Research center for Oral Diseases&department of Periodontics West China Hospital of StomatologySichuan UniversityChengduChina department of Periodontology School and Hospital of StomatologyShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration&Shandong Provincial Clinical Research Center for Oral Diseases JinanJinanChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesDepartment of periodontologySchool of StomatologyThe Fou

Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing *** etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical ***,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal *** compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

关键词： diagnosis periodontal lesions

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Thrombus migration in patients with acute ischaemic stroke undergoing endovascular thrombectomy

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Stroke & Vascular Neurology 2024年第2期9卷 126-133,I0006-I0395页

作者： ZeFeng Tan Lei Zhang Li'an Huang Hongyu Qiao Min Guan Bing Yang Pengfei Yang Yongwei Zhang Hongjian Shen Yu Zhou Bo Hong Huaizhang Shi Hongxing Han Xinyi Leng Yi Dong Changlin Lian Wenhuo Chen Anding Xu Jianmin Liu Neurology First People's Hospital of FoshanFoshanGuangdongChina department of Neurology Jinan University First Affiliated HospitalGuangzhouGuangdongChina Neurovascular center Changhai HospitalNaval Medical UniversityShanghaiChina department of Neurosurgery First Affiliated Hospital of Harbin Medical UniversityHarbinChina department of Neurology Linyi People's HospitalLinyiShandongChina Medicine&Therapeutics The Chinese University of Hong KongHong KongChina Neurology Huashan Hospital Fudan UniversityShanghaiChina Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujianChina Stroke center Jinan University First Affiliated HospitalGuangzhouGuangdongChina

Objective The impact of thrombus migration(TM)prior to endovascular thrombectomy(EVT)on clinical outcomes and revascularisation rates remains *** aimed to examine whether preinterventional TM modifies the treatment effects of direct EVT versus bridging EVT in acute large vessel occlusion *** All patients undergoing catheter angiography in the Direct Intra-arterial thrombectomy in order to Revascularise acute ischaemic stroke patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals:A Multicentre randomised clinical Trial were *** was determined by radiologists unaware of the study by analysing discrepancies between computed tomographic angiography at baseline and first-run digital subtraction angiography before *** primary outcome was the score on the modified Rankin scale(mRS)assessed at 90 *** Of 627 included patients,the TM rate was 11.3%(71/627).In the multivariable logistic regression model,baseline National Institutes of Health Stroke Scale score(adjusted OR 0.956,95%CI 0.916 to 0.999;p=0.043)and intravenous thrombolysis(adjusted OR 2.614,95%CI 1.514 to 4.514;pently associated with *** patients with TM were less likely to be completely recanalised than those without TM(21.27%vs 36.23%,p=0.040).The interaction of TM and the EVT treatment effect did not significantly affect mRS shift analysis(p=0.687)or mRS scores of 0 to 1(p=0.436).Conclusion Preinterventional TM does not modify the treatment effects of direct versus bridging EVT on functional outcomes in patients with acute ischaemic stroke with anterior large vessel *** leads to a lower complete recanalisation rate.

关键词： patients throm acute

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Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

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Asian Journal of Andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-Ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo Yu-Tian Dai Fu-Biao Li Hao-Cheng Lin Zhi-Chao Zhang department of Urology Peking University First HospitalBeijing 100000China department of Urology Peking University Third HospitalBeijing 100191China department of Urology Peking Union Medical College HospitalBeijing 100730China department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China departmentof Andrology Nanjing Drum Tower HospitalNanjing 210008China department of Andrology The First Hospital of Jilin UniversityChangchun 130021China Andrology center Department of UrologyPeking University First HospitalBeijing 100034China

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 ***-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and *** improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,Pents regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,*** Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,*** quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both Pent satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month ***-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

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Biological function of miRNA-145-5p in angiotensin II induced renal inflammation

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BIOCELL 2024年第4期48卷 601-611页

作者： BIN LI YUCHENG SHENG XIAOYING XU SHENGCUN WANG HONGYAN SONG JINGYUAN LI HAONAN JI QINGHUA WANG XIAODI ZHOU LONGJU QI department of Pediatrics Affiliated Hospital of Nantong UniversityNantong226001China department of Science and Education Affiliated Nantong Hospitalof Nantong UniversityNantong226001China Laboratory Animal center Nantong UniversityNantong226001China department of Gynecology and Obstetrics and department of Oncology Hai’an Hospital Affiliated to Nantong UniversityNantong226600China

Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative ***,the therapeutic promise of miR-145-5p in addressing renal pathologies has been *** investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inﬂammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and ***,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)***:AngII incubation induced an upregulation of miR-145-5p and inﬂammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ***,inhibition of miR-145-5p heightened the levels of inﬂammatory factors and cell cycle regulators induced by AngII *** expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII ***,ectopic miR-145-5p expression demonstrated a reduction in inﬂammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall ***:MiR-145-5p exhibited inhibitory effects on the inﬂammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.

关键词： miR-145-5p Kidney Angiotensin II Cell cycle Inflammation

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Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca^(2+)/CaMK2b Pathway

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Neuroscience Bulletin 2024年第4期40卷 421-438页

作者： Yu Xia Lu Ding Changlin Zhang Qi Xu Ming Shi Tianshun Gao Feng-Quan Zhou David Y.B.Deng Scientific Research center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China department of Gynecology The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Pelvic Floor Disorders center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Big Data center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Sir Run Run Shaw hospital Zhejiang University School of MedicineHangzhou310016China Orthopaedic and Neurological Repair center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological ***,the mechanism underlying astrocyte over-proliferation after SCI is ***2c(glutamate ionotropic receptor type 2c)plays an essential role in cell *** bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after *** of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in *** screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage *** of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation ***,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.

关键词： IL1α Grin2c Astrocyte Spinal cord injury

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Randomised study of bailout intracranial angioplasty following thrombectomy for acute large vessel occlusion(ANGEL-REBOOT):protocol of a multicentre randomised controlled trial

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Stroke & Vascular Neurology 2024年第2期9卷 181-188页

作者： Feng Gao Xu Tong Baixue Jia Ming Yang Yuesong Pan Zeguang Ren William Scott Burgin Liping Liu Xingquan Zhao Yilong Wang Yongjun Wang Zhongrong Miao Interventional Neuroradiology Department of NeurologyBeijing Tiantan HospitalBeijingChina China National Clinical Research center for Neurological Diseases Beijing Tiantan HospitalBeijingChina department of Neurosurgery University of South FloridaTampaFloridaUSA department of Neurology Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA Comprehensive Stroke center Tampa General HospitalTampaFloridaUSA department of Neurology Beijing Tiantan HospitalBeijingChina

Rationale Unsuccessful thrombectomy of acute large vessel occlusions(LVOs)has been associated with unfavourable *** randomised controlled trials(RCTs)have reported a failure rate of 12%–41%for thrombectomy *** factors contribute to failed thrombectomy,including technical difficulties in accessing the occlusion,unsuccessful thrombus retrieval,thrombotic reocclusion and pre-existing intracranial atherosclerotic *** some studies have explored balloon dilation or permanent stenting as rescue intracranial angioplasty for failed thrombectomy in individual cases,there is currently no evidence from RCTs on this specific *** To evaluate the potential superiority of bailout angioplasty over standard treatment in cases of unsuccessful recanalisation(eTICI 0 to 2a)or residual severe stenosis(>70%)after thrombectomy in acute LVO patients within 24 hours of stroke *** This study is a multicentre,prospective,randomised,controlled clinical trial designed by *** compares bailout angioplasty with standard therapy and follows an open-label treatment approach while maintaining a blinded outcome assessment(PROBE design).Our objective is to allocate 348 patients in a 1:1 ratio to either receive bailout angioplasty as an intervention or standard therapy as a control,following unsuccessful *** The main measure of interest is the modified Rankin Scale(mRS)Score,which will be assessed in a blinded manner at 90(±14)days following *** primary effect size will be determined using ordered logistic regression to calculate the common OR,representing the shift on the six-category mRS Scale at the 90-day ***,the safety outcomes will be evaluated,including symptomatic intracranial haemorrhage within 18–36hours,severe procedure-related complications and mortality within 90(±14)days,among *** The ANGEL-REBOOT study aims to generate substantial evidence regarding the efficacy

关键词： angioplasty throm intracranial

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Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su Institute of Translational Medicine Shanghai UniversityShanghai 200444China Organoid Research center Shanghai UniversityShanghai 200444China National center for Translational Medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

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Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation

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Neuroscience Bulletin 2024年第2期40卷 255-267页

作者： Yuan Zhang Fanglei Ye Xiaolong Fu Shen Li Le Wang Yutian Chen Hongmin Li Shaojuan Hao Kun Zhao Qi Feng Peipei Li department of Otology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Shandong Provincial hospital Shandong First Medical UniversityJinan 250000China department of Neurology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China The department of Endovascular Surgery The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China department of Integrated Traditional and Western Nephrology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Province Research center of Kidney Disease Zhengzhou 450052China

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and *** regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear *** distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related ***,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains ***,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune *** particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic *** hope this review will provide new perspectives and a basis for future research on cochlear inflammation.

关键词： Macrophage Mitochondria Innate immunity Cochlea Infammation

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Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115

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Cellular & Molecular Immunology 2024年第3期21卷 275-291页

作者： Zhi-Dong Zhang Chang-Rui Shi Fang-Xu Li Hu Gan Yanhong Wei Qianhui Zhang Xin Shuai Min Chen Yu-Lin Lin Tian-Chen Xiong Xiaoqi Chen Bo Zhong Dandan Lin department of Gastrointestinal Surgery Medical Research InstituteFrontier Science Center of Immunology and MetabolismZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan430071China department of Virology College of Life SciencesWuhan UniversityWuhan430072China TaiKang center for Life and Medical Sciences Wuhan UniversityWuhan430071China Wuhan Research center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan430071China department of Rheumatology and Immunology Zhongnan Hospital of Wuhan UniversityWuhan430071China Cancer center Renmin Hospital of Wuhan UniversityWuhan430060China

STING(also known as MITA)is an adaptor protein that mediates cytoplasmic DNA-triggered signaling,and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe ***,we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram(DSF).Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1^(–/–)mice and STING^(N153S/WT) bone marrow chimeric *** addition,knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α,IFN-γand proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus(SLE)who exhibit high concentrations of dsDNA in peripheral ***,knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1^(–/–)***,knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or *** together,these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

关键词： STING/MITA Disulfiram RNF115 SLE Autoimmunity

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