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Congenital Heart disease 2024年第2期19卷 131-138页

作者： Dominique Vervoort Amy Verstappen Sreehari Madhavankutty Nair Chong Chin Eu Bistra Zheleva Institute of Health Policy Management and EvaluationUniversity of TorontoTorontoCanada division of Cardiac Surgery University of TorontoTorontoCanada Global Alliance for rheumatic and Congenital Hearts PhiladelphiaUSA Department of Health Services Government of KeralaKeralaIndia Ministry of Health PutrajayaMalaysia Children’s HeartLink MinneapolisUSA

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

关键词： Congenital heart disease pediatric heart disease global health health systems health policy

Schnitzler syndrome and Schnitzler-like syndromes

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Chinese Medical Journal 2022年第10期135卷 1190-1202页

作者： Cong-Qiu Chu division of Arthritis and rheumatic diseases Oregon Health&Science University and Rheumatology SectionVA Portland Health Care SystemPortlandOR 97239USA

Schnitzler syndrome is a rare disease of adult-onset with main features including chronic urticarial rash, recurrent fever, arthralgia or arthritis, monoclonal gammopathy of undetermined significance (MGUS), and marked systemic inflammation. Schnitzler syndrome is often underdiagnosed. Patients with Schnitzler syndrome may present to dermatologists and allergists for urticaria, hematologists for MGUS, or rheumatologists for arthritis. It is important to recognize Schnitzler syndrome for its remarkable response to interleukin (IL)-1 blockade. Besides, many cases of Schnitzler-like syndromes do not meet the diagnostic criteria of classical Schnitzler syndrome but display excellent response to IL-1 inhibitors. The overly produced IL-1 is the result of a somatic mosaic gain of function mutation ofNLRP3 (nucleotide-binding oligomerization domain [NOD]-like receptor [NLR] family pyrin domain containing 3) gene in some patients with Schnitzler-like syndromes. Inflammasome activation is evident in patients with classical Schnitzler syndrome although noNLRP3 gene mutation is identified. Collectively, Schnitzler syndrome and Schnitzler-like syndromes represent a spectrum of IL-1 mediated adult-onset autoinflammatory diseases.

关键词： Schnitzler syndrome Schnitzler syndrome-like conditions Interleukin-1 Chronic urticarial rash

Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients

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Chinese Medical Journal 2022年第6期135卷 658-664页

作者： Chun Li Yu Zuo Song Zhang Una E.Makris David R.Karp Zhanguo Li Department of Rheumatology and Immunology Peking University People's HospitalBeijing 100044China division of Rheumatology Department of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA division of Biostatistics Department of Clinical SciencesUT Southwestern Medical CenterDallasTXUSA Medical Service VA North Texas Health Care SystemDallasTXUSA division of rheumatic disease Department of Internal MedicineThe University of Texas Southwestern Medical CenterDallasTXUSA

Background:Antiphospholipid syndrome(APS)is an autoimmune prothrombotic condition with significant morbidity.The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis,venous thrombosis,and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies(aPLs)-positive carriers.Methods:This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital.Among 453 patients screened,297 patients had persistent positive aPL.We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients.And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations.The levels of circulating markers of neutrophil extracellular traps(NETs)(cell-free DNA and citrullinated histone H3[Cit-H3])were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.Results:Additional risk factors associated with arterial thrombosis among aPL-positive carriers included:smoking(odds ratio[OR]=6.137,95%confidence interval[CI]=2.408-15.637,P=0.0001),hypertension(OR=2.368,95%CI=1.249-4.491,P=0.008),and the presence of underlying autoimmune disease(OR=4.401,95%CI=2.387-8.113,Pdisease(OR=6.330,95%CI=3.355-11.940,Pdisease(OR=3.301,95%CI=1.407-7.744,P=0.006)is the additional risk,which demonstrated a significant association with APS pregnancy morbidity.Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases.Furthermore,control neutrophils that are conditioned with APS patients'sera have more

关键词： Antiphospholipid antibodies Antiphospholipid syndrome Arterial thrombosis Pregnancy risk Venous thrombosis

Complement-targeted therapy for autoimmune diseases

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Medical Review

Medical Review 2023年第6期3卷 521-525页

作者： Cong-Qiu Chu division of Arthritis and rheumatic diseases Oregon Health&Science UniversityPortlandOR 97239USA Rheumatology Section Veterans Affairs Portland Health Care SystemPortlandOR 97239USA

The success and safety seen in treating complement-mediated hemolysis conditions has sparked the development of targeted therapies for rare autoimmune diseases,with expansion to more common autoimmune conditions.Various classes of drugs,including small molecules,peptides,monoclonal antibodies,and small interfering RNA(siRNA),are undergoing development to specifically address complement activity.A dual approach targeting both complement and other immune components may be required for autoimmune diseases characterized by inflammation and complex pathogenic mechanisms.siRNA,which suppresses complement production,is emerging as a potent therapeutic tool.Combining a complement-blocking siRNA drug with a treatment that reduces autoantibodies could prove clinically feasible and impactful in managing these conditions.

关键词： complement autoimmune diseases siRNA dual target

Preventing rheumatoid arthritis:Lessons from that of type 1 diabetes

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Rheumatology & Autoimmunity 2023年第2期3卷 67-69页

作者： Cong-Qiu Chu division of Arthritis and rheumatic diseases Oregon Health&Science UniversityPortlandOregonUSA Innovent Biologics(USA) RockvilleMarylandUSA

It is widely recognized that treatment intervention in patients with rheumatoid arthritis(RA)at early stages is associated with improved outcomes.1 Hence,research efforts have been devoted to investigation of whether intervention starting at the preclinical stage will prevent the clinical onset of RA.2-5 In these studies,individuals at risk for RA were identified mainly by the detection of anti-citrullinated protein antibodies(ACPAs)and/or the rheumatoid factor(RF),which may precede the clinical symptoms of RA patients.

关键词： rheumatoid clinical patients

Blocking tumor necrosis factor paved the way for targeted therapeutics in inflammatory diseases

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Chinese Medical Journal 2021年第21期134卷 2525-2528页

作者： Cong-Qiu Chu division of Arthritis and rheumatic diseases Oregon Health&Science University and Rheumatology SectionVA Portland Health Care SystemPortlandOR 97239USA

Tumor necrosis factor(TNF)becomes a well-known name largely owing to the success of its antagonists in therapy of inflammatory diseases.[1,2]In 1975,in searching for cancer therapeutic agent.

关键词： inflammatory diseases targeted

Contribution of neutrophils in the pathogenesis of rheumatoid arthritis

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The Journal of Biomedical Research 2020年第2期34卷 86-93页

作者： Lingshu Zhang Yi Yuan Qiang Xu Zhengyu Jiang Cong-Qiu Chu division of Arthritis and rheumatic diseases Oregon Health&Science UniversityPortlandOR 97239USA Rheumatology Section VA Portland Healthcare SystemPortlandOR 97239USA Department of Rheumatology and Immunology the First Hospital of Jilin UniversityChangchunJilin 130021China

Neutrophils are major innate immune effector cells for host defense and have been a topic of active research for their participation in the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis(RA)due to recently discovered neutrophil extracellular trap(NET) formation. NET formation and other mechanisms leading to the release of neutrophil nuclear and cytoplasmic contents are implicated as a source of citrullinated antigens in RA. Further investigations are required to delineate what factors diverge neutrophils from host defense to autoimmune response in RA.

关键词： neutrophils rheumatoid arthritis NET formation

NOD2/CARD15突变的回肠储袋患者的自身免疫性疾病

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Gastroenterology Report 2016年第1期4卷 73-76,I0003页

作者： Darren N.Seril Qingping Yao Bo Shen division of Gastroenterology/Hepatology Albany Medical CollegeAlbanyNew YorkUSA Departments of rheumatic and Immunologic disease The Cleveland Clinic FoundationClevelandOhioUSA Department of Gastroenterology/Hepatology The Cleveland Clinic FoundationClevelandOhioUSA

Pouchitis is common in ulcerative colitis patients undergoing total proctocolectomy with ileal pouch-anal anastomosis,and chronic antibiotic-refractory pouchitis occurs in a subgroup of the patients.Auto-inflammatory diseases are characterized by systemic inflammation,manifesting as periodic fever,rash,arthritis,and serositis.We describe two cases with ulcerative colitis and an ileal pouch,who presented with extra-intestinal manifestations and genetic features atypical for inflammatory bowel disease alone.Case 1 had a spectrum of clinical manifestations including refractory pouchitis,intermittent fevers,polyarthralgia,and pericarditis.Case 2 presented with oral ulcers,migratory oligoarthritis,and periodic papular rash.Genetic testing in both cases revealed mutations of the NOD2/CARD15 gene,including the IVS8þ158 mutation commonly detected among patients with NOD2-associated auto-inflammatory disease.Both of the patients demonstrated clinical improvement of these diverse systemic complaints following treatment with immunosuppressive and anti-inflammatory therapies.

关键词： auto-inflammation ileal pouch pouchitis restorative proctocolectomy ulcerative colitis

Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives

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World Journal of Orthopedics 2014年第4期5卷 496-503页

作者： Charles J Malemud David E Blumenthal The Arthritis Research Laboratory Department of Medicine Division of Rheumatic Diseases Case Western Reserve University Cleveland OH 44106-5076 United States Department of Anatomy Case Western Reserve University Cleveland OH 44106-5076 United States School of Medicine Division of Rheumatology Veteran’s Administration Medical Center Cleveland OH 44106 United States

Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription(JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.

关键词： Clinical trials Protein kinase Signal transduction Small molecule inhibitor Rheumatoid arthritis

Immune tolerance of food is mediated by layers of CD4 + T cell dysfunction

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四川生理科学杂志 2022年第6期44卷 1039-1039页

作者： Sung-Wook Hong Center for Immunology University of Minnesota Medical School Minneapolis MN USA Department of Microbiology and Immunology University of Minnesota Medical School Minneapolis MN USA division of rheumatic and Autoimmune diseases Department of Medicine University of Minnesota Medical School Minneapolis MN USA Minnesota Supercomputing Institute University of Minnesota Minneapolis MN USA

Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food1,2.This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation.Here we addressed this conundrum by using a sensitive cell enrichment method to show that polyclonal CD4+T cells responded to food peptides,including a natural one from gliadin,by proliferating weakly in secondary lymphoid organs of the gut-liver axis owing to the action of regulatory T cells.

关键词： organs Immune lymphoid