31 results on '"Shunli Tang"'
Search Results
2. Bimekizumab for the treatment of moderate-to-severe plaque psoriasis: a meta-analysis of randomized clinical trials
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Yuqian Wang, Sheng Li, Juan Bai, Xiaoxuan Cai, Shunli Tang, Peiyi Lin, Qingmiao Sun, Jianjun Qiao, and Hong Fang
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, and is a promising drug for patients with moderate-to-severe plaque psoriasis. Objectives: This study aimed to assess the efficacy and safety of bimekizumab in treating patients with psoriasis and to determine the optimal maintenance dosing schedules of bimekizumab. Methods and design: Eligible trials were identified from PubMed, Cochrane Controlled Register of Trials, Embase, ClinicalTrials.gov, and Chinese medical databases. Only double-blind, randomized, active comparator, or placebo-controlled trials of bimekizumab treatment on patients with psoriasis were included in this study. Results: Five studies were identified, which included 2473 patients with moderate-to-severe plaque psoriasis. The results indicated that bimekizumab had better efficacy than placebo or active comparator for Psoriasis Area and Severity Index (PASI) 90 [risk ratio (RR) = 29.29, 1.52; 95% confidence interval (CI) = 10.30–83.30, 1.06–2.19], PASI 100 (RR = 59.87, 2.06; 95% CI = 15.06–237.99, 1.12–3.79), and Investigator’s Global Assessment scores of 0 or 1 (IGA 0/1) (RR = 21.55, 1.36; 95% CI = 9.25–50.19, 1.02–1.81). Faster onset of clinically meaningful responses was observed with bimekizumab compared with both active comparators (RR = 2.59; 95% CI = 1.32–5.10) and placebo (RR = 40.46; 95% CI = 13.19–124.13), with PASI 75 response observed at week 4 after one dose. Subgroup analysis showed no significant difference in the reduction of PASI scores between 320 mg q4w dosage and q8w dosage (RR = 1.00; 95% CI = 0.96–1.03). Rates of patients with adverse events (AEs) were comparable in the bimekizumab and active comparator groups (RR = 1.13; 95% CI = 1.01–1.26), and oral candidiasis was one of the most common treatment-emergent AEs. Conclusion: The results of this meta-analysis suggest that bimekizumab is more efficacious and has a rapid onset of action than active comparators and placebo in the treatment of moderate-to-severe plaque psoriasis. After 16 weeks of initial maintenance treatment, both bimekizumab maintenance dosing schedules (320 mg every 4 and 8 weeks) had similar efficacy.
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- 2023
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3. Risk factors of cardiovascular involvement in patients with Behcet's disease
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Yuqian Wang, Sheng Li, Shunli Tang, Xiaoxuan Cai, Juan Bai, Qingmiao Sun, Jianjun Qiao, and Hong Fang
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Behcet's disease ,Cardiovascular involvement ,Clinical characteristics ,Risk factors ,Vasculitis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Objectives: Behcet's disease (BD) is a multi-systemic inflammatory vasculitis which may be life-threatening if combined with cardiovascular problems. The aim of the study was to identify potential risk factors associated with cardiovascular involvement in BD. Methods: We reviewed the medical databases of a single center. All BD patients identified as fulfilling the 1990 International Study Group criteria or the International Criteria for Behcet's Disease criteria. Cardiovascular involvement, clinical manifestations, laboratory features, and treatments were recorded. The relationship between parameters and cardiovascular involvement was analyzed. Results: 111 BD patients were included: 21 (18.9%) had documented cardiovascular involvement (CV BD group) and 99 (81.1%) had no cardiovascular involvement (non-CV BD group). Compared with non-CV BD, the proportion of males and smokers were significantly increased in CV BD (p = 0.024 and p
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- 2023
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4. Biologic TNF-alpha inhibitors in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a systemic review
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Shan Zhang, Shunli Tang, Sheng Li, Yunlei Pan, and Yingguo Ding
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tnf-alpha inhibitors ,toxic epidermal necrolysis ,steven-johnson syndrome ,Dermatology ,RL1-803 - Abstract
Background: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) is one of severe cutaneous adverse reactions with low morbidity but high mortality. Different systemic immunomodulating treatments are proposed but still remain controversial. Tumor necrosis factor (TNF)-alpha is long thought to be a vital mediator of epithelial cell death in SJS-TEN, indicating a potential target for therapy. Objective: The aim of this systemic review is to evaluate the efficacy and safety of biologic TNF-alpha inhibitors in the treatment of SJS-TEN. Methods: We reviewed the published literature by searching from PubMed, EMBASE, Web of Science and ClinicalTrial.gov. A total of 27 articles fulfilling our inclusion criteria were found and analyzed. Results: There were 21 case reports, four case series and two randomized controlled trials (RCTs) on the biologic TNF-alpha inhibitors for SJS-TEN therapy, comprising 91 patients. TNF-alpha inhibitors were used as monotherapy, second-line therapy or combination therapy. Among them, 79 patients (86.8%) responded well and discharged with few side effects and complications. Conclusions: Biologic TNF-alpha inhibitors are a safe and effective treatment for SJS-TEN. But further, larger RCTs need to be conducted to provide more evidence for clinical application.
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- 2020
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5. Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification
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Changyi Yang, Shunli Tang, Dingxian Zhu, Yingguo Ding, and Jianjun Qiao
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anti-topoisomerase antibodies ,anticentromere antibodies ,anti-RNA polymerase antibodies ,systemic sclerosis ,clinical manifestations ,gene ,Medicine (General) ,R5-920 - Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by abnormalities in microcirculation, extracellular matrix accumulation, and immune activation. Autoantibodies are markers of immune abnormalities and provide diagnostic and predictive value in SSc. Anti-topoisomerase antibodies (ATAs), anticentromere antibodies (ACAs), and anti-RNA polymerase antibodies (ARAs) are the three classical specific antibodies with the highest availability and stability. In this review, we provide an overview of the recent progress in SSc research with respect to ATAs, ACAs, and ARAs, focusing on their application in distinguishing clinical phenotypes, such as malignancy and organ involvement, identifying genetic background in human leukocyte antigen (HLA) or non-HLA alleles, and their potential roles in disease pathogenesis based on the effects of antigen–antibody binding. We finally summarized the novel analysis using ATAs, ACAs, and ARAs on more detailed disease clusters. Considering these advantages, this review emphasizes that classical SSc-specific autoantibodies are still practical and have the potential for patient and risk stratification with applications in precise medicine for SSc.
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- 2020
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6. The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside
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Taoming Liu, Sheng Li, Shuni Ying, Shunli Tang, Yuwei Ding, Yali Li, Jianjun Qiao, and Hong Fang
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IL-17 family ,IL-23 ,IL-23/IL-17 axis ,psoriasis ,targeted therapy ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4+ helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.
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- 2020
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7. Insights Into the Characteristics of Sweet Syndrome in Patients With and Without Hematologic Malignancy
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Siting Zheng, Sheng Li, Shunli Tang, Yunlei Pan, Yuwei Ding, Jianjun Qiao, and Hong Fang
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Sweet syndrome ,hematologic malignancy ,treatment ,outcome ,mortality ,Medicine (General) ,R5-920 - Abstract
Background: Sweet syndrome is a neutrophilic dermatosis that could be associated with malignancy, especially hematologic malignancy. Few studies have systematically elaborated on this disorder and its features related with hematologic malignancy.Objective: This study aimed to describe the clinicopathological characteristics, treatment, and outcome of Sweet syndrome and to evaluate patient characteristics associated with hematologic malignancy.Methods: We retrospectively reviewed patients with Sweet syndrome at the Department of Dermatology, the First Affiliated Hospital of Zhejiang University from October 2010 to February 2019.Results: The study included 37 patients (16 men and 21 women), with a mean age of 53 years. Ten patients (27%) were classified as having malignancy-associated Sweet syndrome: nine with a hematologic malignancy including acute myeloid leukemia (4/9, 44%), myelodysplastic syndrome (4/9, 44%), and multiple myeloma (1/9, 11%) and one with a solid tumor diagnosed with liver carcinoma. The mean hemoglobin and platelet levels (P = 0.007 and P = 0.013, respectively), were significantly lower in patients with hematologic malignancy than in those with Sweet syndrome only. No significant difference in histopathology was found between patients with and without hematologic malignancy. Systemic corticosteroids were the most frequently used treatment (24/37, 65%). Higher mortality was found in patients with hematologic malignancy.Conclusion: It is important to assess Sweet syndrome patients who have laboratory evidence of lower hemoglobin and platelet levels for a hematologic malignancy.
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- 2020
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8. Clinical Features of Macrophage Activation Syndrome in Adult Dermatomyositis: A Single-Center Retrospective Cohort Study
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Dingxian Zhu, Shuni Ying, Changyi Yang, Juan Bai, Sheng Li, Shunli Tang, Chuanyin Sun, Liangshun You, Hong Fang, and Jianjun Qiao
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- 2023
9. Efficacy and safety of baricitinib in patients with refractory alopecia areata
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Yuqian Wang, Taoming Liu, Sheng Li, Shunli Tang, Peiyi Lin, Yuwei Ding, Qingmiao Sun, Dingxian Zhu, Jianjun Qiao, and Hong Fang
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Alopecia Areata ,Purines ,Humans ,Azetidines ,Dermatology ,General Medicine - Published
- 2022
10. Genetic and pharmacological targeting of GSDMD ameliorates systemic inflammation in macrophage activation syndrome
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Shunli Tang, Changyi Yang, Sheng Li, Yuwei Ding, Dingxian Zhu, Shuni Ying, Chuanyin Sun, Yu Shi, Jianjun Qiao, and Hong Fang
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Immunology ,Immunology and Allergy - Abstract
Macrophage activation syndrome (MAS), a potentially life-threatening complication of autoimmune/autoinflammatory diseases, is characterized by the excessive expansion and activation of macrophages and cytotoxic T lymphocytes in multiple organs. Most commonly, MAS occurs in patients with systemic juvenile idiopathic arthritis and in its adult equivalent, adult-onset Still's disease (AOSD). Gasdermin D (GSDMD) is a critical pore-forming effector protein that mediates pro-inflammatory cytokine secretion via releasing its N terminal fragments to form transmembrane pores. GSDMD has been implicated in various inflammatory diseases, however, its role in MAS remains elusive. Here, we unveiled that the serum levels of GSDMD-N were elevated in patients with AOSD compared to heathy controls. In addition, the emergence of MAS features in AOSD patients resulted in further elevation. The serum levels of GSDMD were positively correlated with ferritin and interleukin-18 (IL-18). Repeated toll-like receptor 9 stimulation with unmethylated cytosine-phosphate-guanine (CpG) induced MAS symptoms in wild-type mice, including body weight loss, pancytopenia and hepatosplenomegaly. Genetic deletion and pharmacological inhibition of GSDMD ameliorated MAS symptoms in mice with the concomitant reduction of splenic and hepatic macrophage infiltration and IL-18 production. Consistent with these in vivo results, bone marrow-derived macrophages obtained from GSDMD
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- 2022
11. Understanding of cytokines and targeted therapy in macrophage activation syndrome
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Shunli Tang, Siting Zheng, Jianjun Qiao, Dingxian Zhu, Sheng Li, Yuwei Ding, Chuanyin Sun, Hong Fang, and Yongxian Hu
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Adult ,musculoskeletal diseases ,medicine.medical_treatment ,Arthritis ,Disease ,Systemic inflammation ,Targeted therapy ,Pathogenesis ,Rheumatology ,medicine ,Humans ,business.industry ,Macrophage Activation Syndrome ,fungi ,medicine.disease ,Arthritis, Juvenile ,Anesthesiology and Pain Medicine ,Macrophage activation syndrome ,Immunology ,Cyclosporine ,Cytokines ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Complication ,Cytokine storm ,business ,Still's Disease, Adult-Onset ,hormones, hormone substitutes, and hormone antagonists - Abstract
Macrophage activation syndrome (MAS) is a potentially life-threatening complication of systemic autoinflammatory/autoimmune diseases, generally systemic juvenile idiopathic arthritis and adult-onset Still's disease. It is characterized by an excessive proliferation of macrophages and T lymphocytes. Recent research revealed that cytokine storm with elevated pro-inflammatory cytokines, including IFN-γ, IL-18, and IL-6, may be central to the pathogenesis of MAS. Though the mainstream of MAS treatment remains corticosteroids and cyclosporine, targeted therapies with anti-cytokine biologics are reported to be promising for controlling systemic inflammation in MAS.
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- 2021
12. Underlying Systemic Diseases in Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: A Systematic Review
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Changyi Yang, Shunli Tang, Sheng Li, Shuni Ying, Dingxian Zhu, Taoming Liu, Yuqi Chu, Hong Fang, and Jianjun Qiao
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Dermatology - Abstract
Background: Interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD) are uncommon presentations of reactive granulomatous dermatitis. Histologic lesions characterized by IGD/PNGD patterns have been associated with systemic diseases, causing an unmet need for revealing clinical correlates. Objective: The aim of this study was to unravel the systemic diseases beyond dermatitis of IGD/PNGD. Methods: This study analyzed data from case studies, case series, and retrospective cohorts by searching PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions on Sep 4, 2021. Results: One hundred ninety-six publications were included (458 cases in total, 216 with details). Systemic diseases associated with IGD/PNGD were classified into 5 groups. Autoimmune disorders (n = 103, 47.6%) including rheumatoid arthritis (n = 51, 23.6%), systemic lupus erythematosus (n = 20, 9.3%), and others were the most common across all underlying diseases, followed by drug eruption (n = 52, 24.1%) such as tumor necrotic factor inhibitor reaction (n = 18, 8.3%) and malignancies (n = 27, 12.5%) such as hematologic malignancy (n = 20, 9.3%). The rest were infectious diseases (n = 12, 5.6%) and accidental conditions (n = 3, 1.4%). Conclusion: IGD/PNGD might be associated with autoimmune disorders, drug eruption, malignancies, infectious diseases, and accidental conditions. Patients with IGD/PNGD need further follow-up.
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- 2022
13. Immune-Mediated Necrotizing Myopathy Initially Presenting as Erythema Nodosum
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Deren Fang, Shuni Ying, Yali Li, Jianjun Qiao, Hong Fang, Shunli Tang, Sheng Li, Dingxian Zhu, and Qingmiao Sun
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0301 basic medicine ,Erythema nodosum ,Necrosis ,biology ,Immune mediated necrotizing myopathy ,business.industry ,Immunology ,Autoantibody ,Context (language use) ,medicine.disease ,Inflammatory myopathy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,biology.protein ,medicine ,Immunology and Allergy ,Rituximab ,Antibody ,medicine.symptom ,business ,medicine.drug - Abstract
Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by severe diffuse proximal myofiber necrosis in the context of inflammatory myopathy. Autoantibodies of anti-signal recognition particle and anti-hydroxy-3-methylglutaryl-CoA reductase are two antibodies specific to IMNM. Erythema nodosum (EN) is often accompanied by various systemic diseases, such as autoimmune diseases. Herein, we report a female patient with signal recognition particle-associated IMNM, with EN as the first presentation. She showed significant clinical improvement after the initiation of glucocorticoids, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. This case indicates that IMNM can initially present as EN. IMNM and EN might have overlapping pathogeneses.
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- 2020
14. Digital Image Analysis-Based Evaluation of Claudin-1 and Claudin-7 Delocalization in Cutaneous Squamous Cell Carcinoma and in Its Precancerous State
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Lina Xu, Yunlei Pan, Shunli Tang, Juan Bai, Yinhua Wu, Jianjun Qiao, and Hong Fang
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Oncology ,endocrine system diseases ,Article Subject ,urologic and male genital diseases ,tissues ,digestive system ,digestive system diseases - Abstract
Accumulating evidence has revealed that delocalization of the transmembrane proteins, Claudin-1 and Claudin-7, to the cytoplasm and/or nucleus occurs in various tumors. However, their subcellular distribution in terms of the membrane, cytoplasm, and nucleus and relationship with signaling pathways have not been elucidated during carcinogenesis. We first determined the expression of these proteins in the membrane, cytoplasm, and nucleus using ImageJ software and automatically collected the immunohistochemical quantification of dysplasia (actinic keratosis (AK)), carcinoma in situ (CIS; Bowen’s disease (BD)), and invasive cutaneous squamous cell carcinoma (SCC) for digital image analysis (DIA). The activity of p-ERK, p-AKT, and p-mTOR and their correlation with subcellular Claudin-1 and Claudin-7 were also performed. Finally, we validated Claudin-1 and Claudin-7 delocalization at the cytoplasm and nucleus in cultured human normal keratinocytes and cutaneous SCC cells. Claudin-1 and Claudin-7 were delocalized as revealed by membranous, cytoplasmic, and nuclear staining in sun-exposed skin, AK, BD, and SCC. In BD, both membranous and cytoplasmic Claudin-1 (nuclear Claudin-1 decrease but no significant difference) were higher than AK, while Claudin-7 almost had the opposite situation. In SCC, cytoplasmic and nuclear Claudin-1 (membranous Claudin-1 no significant difference) was lower than in AK and sun-exposed skin, while Claudin-7 had higher membranous and cytoplasmic but lower nuclear expression. Moreover, p-AKT and p-mTOR (but not p-ERK) were downregulated in the SCC. Subcellular Claudin-1 and Claudin-7 were not only correlated with each other, but also correlated with p-ERK in BD and p-AKT and p-mTOR in SCC. Together, these results imply the delocalization of Claudin-1 and Claudin-7 and their correlation with MAPK/ERK and PI3K-AKT-mTOR signaling pathways in tumorigenesis and infiltration in cutaneous SCC.
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- 2022
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15. Adult-Onset Still Disease Presenting With Dermatomyositis-Like Persistent Pruritic Lesions
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Hong Fang, Chuanyin Sun, Siting Zheng, Jianjun Qiao, Sheng Li, Dingxian Zhu, Yunlei Pan, and Shunli Tang
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Adult ,medicine.medical_specialty ,Still's disease ,Still Disease ,Dermatology ,Disease ,Dermatomyositis ,Pathology and Forensic Medicine ,Diagnosis, Differential ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,business.industry ,Pruritus ,General Medicine ,Exanthema ,medicine.disease ,Rash ,Adult-Onset Still Disease ,Female ,medicine.symptom ,business ,Still's Disease, Adult-Onset - Abstract
Adult-onset Still disease (AOSD) is a rare autoinflammatory condition. The presence of an evanescent, salmon-pink, nonpruritic rash is one of the major diagnostic criteria for the disease. The rash occurs with fever and subsides with defervescence. The presence of dyskeratotic keratinocytes in the upper one-third layer of the epidermis is a distinctive histopathological feature of persistent pruritic lesions associated with AOSD. Here, we report 2 cases of AOSD characterized by persistent pruritic lesions resembling those observed in dermatomyositis. Identifying the clinical and histopathological manifestation of the cutaneous lesions is essential for the early diagnosis of AOSD and for differentiating this condition from those presenting with dyskeratotic cells in the epidermis.
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- 2019
16. Possible magnetic rotational band in 77Kr.
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Shuifa Shen, Chuangye He, Yupeng Yan, Weiliang Qian, Feipeng Wang, Guangyong Pan, Jun Chen, Jinlan Jiang, Jiejie Shen, Shunli Tang, Fumin Zou, Haibin Jiang, Tianjan Li, Lina Bao, Tingtai Wang, and Jiaming Jiang
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NUCLEAR energy ,HEAVY ion fusion reactions ,ACCELERATOR mass spectrometry ,MAGNETIC dipoles - Abstract
High-spin states of 77Kr are studied via the fusion-evaporation reaction 68Zn(16O, 2p5n)77Kr with the beam energy of 80 MeV provided by the Tandem accelerator at Japan Atomic Energy Agency (JAEA). The intensity of the beam is I x 1 pnA. In the present work, some new transitions are found to constitute the new band of the proposed level scheme. It is very similar to the M1 transition from the level energy, so it is proposed that this band is the M1 band. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Elevated carcinoembryonic antigen predicts rapidly progressive interstitial lung disease in clinically amyopathic dermatomyositis
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Dingxian Zhu, Sheng Li, Yunlei Pan, Shunli Tang, Changyi Yang, Jianjun Qiao, and Hong Fang
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Male ,medicine.medical_specialty ,Malignancy ,Logistic regression ,Severity of Illness Index ,Gastroenterology ,Dermatomyositis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,Rheumatology ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Risk factor ,Retrospective Studies ,030203 arthritis & rheumatology ,biology ,business.industry ,Incidence (epidemiology) ,Interstitial lung disease ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Carcinoembryonic Antigen ,Amyopathic dermatomyositis ,Disease Progression ,biology.protein ,Female ,Lung Diseases, Interstitial ,business - Abstract
Objectives The present study aimed to determine the correlation between serum carcinoembryonic antigen (CEA) level and the severity of interstitial lung disease (ILD) in clinically amyopathic DM (CADM) patients. Methods We performed a retrospective study including 41 Chinese CADM patients without malignancy. Serum CEA levels, clinical and laboratory findings were collected. Association tests between CEA levels and disease activity parameters were performed. Results Among the 41 patients, 16 (39.0%) developed rapidly progressive (RP)-ILD; of them, 14 (87.5%) had elevated serum CEA levels. Multivariate logistic regression analysis indicated that an elevated serum CEA level was an independent risk factor for RP-ILD. The incidence of elevated CEA level was significantly higher in patients with RP-ILD than in those without RP-ILD (87.5 vs 16.0%, P 8.75 μg/l than that in the group with a CEA level Conclusions An elevated serum CEA level is common in patients with CADM, and a higher serum CEA level is a powerful indicator of RP-ILD and poor prognosis in those patients.
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- 2021
18. Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification
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Jianjun Qiao, Yingguo Ding, Shunli Tang, Dingxian Zhu, and Changyi Yang
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0301 basic medicine ,systemic sclerosis ,Human leukocyte antigen ,Disease ,Review ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Allele ,skin and connective tissue diseases ,anti-RNA polymerase antibodies ,gene ,030203 arthritis & rheumatology ,Autoimmune disease ,lcsh:R5-920 ,clinical manifestations ,biology ,business.industry ,Autoantibody ,anticentromere antibodies ,General Medicine ,medicine.disease ,anti-topoisomerase antibodies ,disease stratification ,030104 developmental biology ,Immunology ,biology.protein ,Medicine ,Antibody ,Anti-topoisomerase antibodies ,lcsh:Medicine (General) ,business - Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by abnormalities in microcirculation, extracellular matrix accumulation, and immune activation. Autoantibodies are markers of immune abnormalities and provide diagnostic and predictive value in SSc. Anti-topoisomerase antibodies (ATAs), anticentromere antibodies (ACAs), and anti-RNA polymerase antibodies (ARAs) are the three classical specific antibodies with the highest availability and stability. In this review, we provide an overview of the recent progress in SSc research with respect to ATAs, ACAs, and ARAs, focusing on their application in distinguishing clinical phenotypes, such as malignancy and organ involvement, identifying genetic background in human leukocyte antigen (HLA) or non-HLA alleles, and their potential roles in disease pathogenesis based on the effects of antigen–antibody binding. We finally summarized the novel analysis using ATAs, ACAs, and ARAs on more detailed disease clusters. Considering these advantages, this review emphasizes that classical SSc-specific autoantibodies are still practical and have the potential for patient and risk stratification with applications in precise medicine for SSc.
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- 2020
- Full Text
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19. Risk of macrophage activation syndrome in patients with adult-onset Still's disease with skin involvement: A retrospective cohort study
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Sheng Li, Yuwei Ding, Yu Shi, Shunli Tang, Dingxian Zhu, Shuni Ying, Taoming Liu, Chuanyin Sun, Jianjun Qiao, Changyi Yang, Hong Fang, and Weiqian Chen
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Adult ,Adult-onset Still's disease ,medicine.medical_specialty ,Dermatology ,Disease ,medicine ,Humans ,In patient ,Aspartate Aminotransferases ,Retrospective Studies ,biology ,medicine.diagnostic_test ,business.industry ,Macrophage Activation Syndrome ,C-reactive protein ,Hazard ratio ,Retrospective cohort study ,Exanthema ,medicine.disease ,Macrophage activation syndrome ,Erythrocyte sedimentation rate ,Splenomegaly ,biology.protein ,business ,Still's Disease, Adult-Onset - Abstract
Small case series and case reports indicated that atypical persistent pruritic eruptions (PPEs), another type of skin lesions seen in adult-onset Still's disease (AOSD), imply a worse prognosis than typical evanescent rashes.To investigate clinical characteristics and macrophage activation syndrome (MAS) occurrence in AOSD with PPEs.A retrospective cohort study analyzed 150 patients with AOSD with rashes at the First Affiliated Hospital of Zhejiang University from January 2013 to December 2019.Patients with AOSD with PPEs had higher lactate dehydrogenase (492.00 U/L vs 382.00 U/L; P .001) and ferritin (6944.10 ng/ml vs 4286.60 ng/ml; P = .033), and lower fibrinogen (5.05 g/L vs 5.77 g/L; P = .014) than those with evanescent rashes. Patients with AOSD with PPEs had a higher incidence (17.4% vs 3.1%, P = .006) and cumulative event rate for MAS (P = .008) and tended to receive high-dose glucocorticoid (36% vs 20.3%; P = .036). Multivariate analysis indicated that PPEs (hazard ratio [HR], 5.519; 95% confidence interval [CI], 1.138-26.767; P = .034), aspartate aminotransferase of greater than 120 U/L (HR, 8.084; 95% CI, 1.728-37.826; P = .008), and splenomegaly (HR, 21.152; 95% CI, 2.263-197.711; P = .007) were independent risk factors for MAS.Single-center, retrospective nature, small sample size.PPEs indicated increased severity and MAS occurrence versus evanescent rashes. PPEs, aspartate aminotransferase of greater than 120 U/L, and splenomegaly were risk factors for MAS in AOSD with skin involvement.
- Published
- 2020
20. The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside
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Shunli Tang, Yuwei Ding, Shuni Ying, Hong Fang, Jianjun Qiao, Yali Li, Taoming Liu, and Sheng Li
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Mini Review ,Immunology ,Interleukin-23 ,Skin Diseases ,03 medical and health sciences ,0302 clinical medicine ,IL-23 ,Psoriasis ,medicine ,Immunology and Allergy ,Animals ,Humans ,Hidradenitis suppurativa ,Skin ,IL-17 family ,Inflammation ,business.industry ,IL-23/IL-17 axis ,Innate lymphoid cell ,Interleukin-17 ,Atopic dermatitis ,psoriasis ,medicine.disease ,targeted therapy ,Pemphigus ,030104 developmental biology ,Th17 Cells ,Pityriasis rubra pilaris ,Tumor necrosis factor alpha ,Interleukin 17 ,business ,lcsh:RC581-607 ,030215 immunology - Abstract
Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4+ helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.
- Published
- 2020
21. Insights Into the Characteristics of Sweet Syndrome in Patients With and Without Hematologic Malignancy
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Jianjun Qiao, Yuwei Ding, Shunli Tang, Yunlei Pan, Siting Zheng, Hong Fang, and Sheng Li
- Subjects
medicine.medical_specialty ,Malignancy ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Hematologic malignancy ,medicine ,In patient ,Multiple myeloma ,Original Research ,lcsh:R5-920 ,treatment ,business.industry ,Sweet Syndrome ,Significant difference ,Sweet syndrome ,Myeloid leukemia ,General Medicine ,medicine.disease ,mortality ,030220 oncology & carcinogenesis ,outcome ,Medicine ,hematologic malignancy ,Histopathology ,lcsh:Medicine (General) ,business - Abstract
Background: Sweet syndrome is a neutrophilic dermatosis that could be associated with malignancy, especially hematologic malignancy. Few studies have systematically elaborated on this disorder and its features related with hematologic malignancy. Objective: This study aimed to describe the clinicopathological characteristics, treatment, and outcome of Sweet syndrome and to evaluate patient characteristics associated with hematologic malignancy. Methods: We retrospectively reviewed patients with Sweet syndrome at the Department of Dermatology, the First Affiliated Hospital of Zhejiang University from October 2010 to February 2019. Results: The study included 37 patients (16 men and 21 women), with a mean age of 53 years. Ten patients (27%) were classified as having malignancy-associated Sweet syndrome: nine with a hematologic malignancy including acute myeloid leukemia (4/9, 44%), myelodysplastic syndrome (4/9, 44%), and multiple myeloma (1/9, 11%) and one with a solid tumor diagnosed with liver carcinoma. The mean hemoglobin and platelet levels (P = 0.007 and P = 0.013, respectively), were significantly lower in patients with hematologic malignancy than in those with Sweet syndrome only. No significant difference in histopathology was found between patients with and without hematologic malignancy. Systemic corticosteroids were the most frequently used treatment (24/37, 65%). Higher mortality was found in patients with hematologic malignancy. Conclusion: It is important to assess Sweet syndrome patients who have laboratory evidence of lower hemoglobin and platelet levels for a hematologic malignancy.
- Published
- 2020
22. Evaluation of Serum Proinflammatory Cytokine IL-17A and Tight Junction Protein Claudin-1 in Psoriasis.
- Author
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Lina Xu, Yunlei Pan, Shunli Tang, Juan Bai, Yinhua Wu, Jianjun Qiao, and Hong Fang
- Abstract
Objective: This study aimed to estimate serum IL-17A and Claudin-1 levels, investigate their correlation, and evaluate their diagnostic significance as potential blood-based biomarkers in psoriasis. Methods: Serum IL-17A and Claudin-1 concentrations were determined using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to determine differences in serum levels of IL-17A and Claudin-1, their bivariable correlation with psoriasis severity, as Psoriasis Area Severity Index (PASI), and their predictive abilities using receiver operating characteristic (ROC) curves. Results: Significantly higher IL-17A and lower Claudin-1 levels were found in psoriasis (p < 0.05). PASI did not correlate significantly with either IL-17A or Claudin-1 in psoriasis and their subtypes. The only significant correlation between serum IL-17A and Claudin-1 was shown in late-onset psoriasis (r = 0.630, p = 0.028). ROC curve analysis indicated the serum IL-17A, serum Claudin-1, and combination of IL-17A and serum Claudin-1 for predicting psoriasis with the areas under the curve (AUC) of 0.951 (p < 0.0001), 0.709 (p = 0.0119), and 0.949 (p < 0.0001), respectively. Moreover, the potential role in distinguishing between early-onset and late-onset psoriasis: we obtained serum IL-17A, serum Claudin-1, and their combination AUC of 0.590 (p = 0.3126), 0.741 (p = 0.0045), and 0.741 (p = 0.0067), respectively. However, none of the serum IL-17A, serum Claudin-1, and their combination was well-performed discriminating mild psoriasis from moderate-to-severe psoriasis with AUC of 0.553 (p = 0.5596), 0.518 (p = 0.8539), and 0.559 (p = 0.5225), respectively. Conclusion: These preliminary results suggest that the serum Claudin-1 as a potential biomarker and the relationship and possible regulatory interactions between IL-17A and Claudin-1 in psoriasis are distinguishable by age of onset. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
23. Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome
- Author
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Shunli Tang, Jing Wang, Fangying Xu, Wei Yin, Shuai Zhang, Dan Zhou, Yuan Zhou, Tao Zhu, Hong Deng, Zhenli Li, Xiaohong Xu, Maode Lai, Hui Li, Yimin Zhu, Xiaoyang Yin, Dandan Zhang, and Qiong Huang
- Subjects
Adult ,Male ,0301 basic medicine ,China ,Cancer Research ,DNA Copy Number Variations ,Colorectal cancer ,Down-Regulation ,Biology ,Germline ,03 medical and health sciences ,Tumor budding ,Risk Factors ,medicine ,Humans ,Copy-number variation ,Intestinal Mucosa ,Sequence Deletion ,Laser capture microdissection ,Genome, Human ,Epithelial Cells ,Exons ,General Medicine ,Middle Aged ,medicine.disease ,Primary tumor ,Fold change ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Case-Control Studies ,Vesicular Monoamine Transport Proteins ,Cancer cell ,Cancer research ,Female ,Stromal Cells ,Colorectal Neoplasms ,Genome-Wide Association Study - Abstract
Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10-5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17-0.62, 0.12-0.57 and 0.37-0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration.
- Published
- 2017
24. Association between serum ferritin and the severity of drug eruptions
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Hong Fang, Siting Zheng, Shunli Tang, Yunlei Pan, Jianjun Qiao, Dingxian Zhu, and Sheng Li
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Drug ,medicine.medical_specialty ,drug eruptions ,media_common.quotation_subject ,Clinical Biochemistry ,Severity of Illness Index ,Gastroenterology ,03 medical and health sciences ,severe cutaneous adverse drug reaction ,0302 clinical medicine ,White blood cell ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Serum ferritin ,Research Articles ,Aged ,Retrospective Studies ,media_common ,Aged, 80 and over ,Receiver operating characteristic ,biology ,business.industry ,ferritin ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,Area under the curve ,Hematology ,Middle Aged ,medicine.disease ,Confidence interval ,Drug eruption ,Ferritin ,Medical Laboratory Technology ,030104 developmental biology ,medicine.anatomical_structure ,ROC Curve ,030220 oncology & carcinogenesis ,Ferritins ,biology.protein ,Female ,business ,Research Article - Abstract
Background Early recognition and treatment for severe drug eruption are important in improving clinical outcomes. A few studies have reported laboratory parameters to evaluate the severity of drug eruptions. This study aimed to determine the association between serum ferritin and the severity of drug eruptions. Methods We retrospectively reviewed patients diagnosed with drug eruptions in our hospital from 2013 to 2018. Results We identified 85 patients (mean age 53.4 years), 20 in the severe cutaneous adverse drug reactions (SCADRs) group and 65 in the non‐SCADRs group. Serum ferritin level was higher in the SCADRs group compared with that in the CADRs group (P
- Published
- 2019
25. Expression and correlation of interleukin-36γ, claudin-1 and claudin-7 in psoriasis
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Lina Xu, Yunlei Pan, Shunli Tang, Jianjun Qiao, Siting Zheng, and Hong Fang
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Adult ,Male ,Adolescent ,Dermatology ,Severity of Illness Index ,Tight Junctions ,Correlation ,Young Adult ,Text mining ,Psoriasis ,Severity of illness ,Claudin-1 ,medicine ,lcsh:Dermatology ,Humans ,Young adult ,Claudin ,Aged ,business.industry ,Case-control study ,Interleukin ,lcsh:RL1-803 ,Middle Aged ,medicine.disease ,Infectious Diseases ,Case-Control Studies ,Immunology ,Claudins ,Female ,Epidermis ,business ,Interleukin-1 - Published
- 2019
26. Autoinflammatory Pathogenesis and Targeted Therapy for Adult-Onset Still's Disease
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Shunli Tang, Yunlei Pan, Siting Zheng, Hong Fang, Sheng Li, Shan Zhang, and Jianjun Qiao
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0301 basic medicine ,medicine.medical_treatment ,Arthritis ,Autoimmunity ,Disease ,Proinflammatory cytokine ,Targeted therapy ,Autoimmune Diseases ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,Humans ,Leukocytosis ,Molecular Targeted Therapy ,030203 arthritis & rheumatology ,business.industry ,Disease Management ,General Medicine ,medicine.disease ,Rash ,030104 developmental biology ,Immunology ,Etiology ,Cytokines ,Disease Susceptibility ,medicine.symptom ,business ,Still's Disease, Adult-Onset ,Biomarkers - Abstract
Adult-onset Still's disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology. AOSD is generally characterized by high spiking fever, arthralgia or arthritis, skin rash, leukocytosis, and hyperferritinemia. Traditionally, AOSD has been treated with non-steroidal anti-inflammatory drugs, corticosteroids, and immunosuppressants. An increasing number of studies have shown that proinflammatory cytokines, such as interleukin-1β, -18, -6, and tumor necrosis factor-α, play key roles in AOSD and may serve as therapeutic targets. In the current review, we provided insights into the roles of these cytokines in the pathogenesis of AOSD and also provided a commentary on the clinical studies of biologic therapy against AOSD.
- Published
- 2019
27. Biologic TNF-alpha inhibitors in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a systemic review
- Author
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Yingguo Ding, Shunli Tang, Yunlei Pan, Sheng Li, and Shan Zhang
- Subjects
Oncology ,medicine.medical_specialty ,Web of science ,Combination therapy ,Dermatology ,law.invention ,Etanercept ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Effective treatment ,Humans ,Randomized Controlled Trials as Topic ,030203 arthritis & rheumatology ,business.industry ,Tumor Necrosis Factor-alpha ,High mortality ,Antibodies, Monoclonal ,Stevens johnson ,medicine.disease ,Toxic epidermal necrolysis ,stomatognathic diseases ,Treatment Outcome ,Stevens-Johnson Syndrome ,Tumor necrosis factor alpha ,Dermatologic Agents ,business - Abstract
Background: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) is one of severe cutaneous adverse reactions with low morbidity but high mortality. Different systemic immunomodulating treatments are proposed but still remain controversial. Tumor necrosis factor (TNF)-alpha is long thought to be a vital mediator of epithelial cell death in SJS-TEN, indicating a potential target for therapy.Objective: The aim of this systemic review is to evaluate the efficacy and safety of biologic TNF-alpha inhibitors in the treatment of SJS-TEN.Methods: We reviewed the published literature by searching from PubMed, EMBASE, Web of Science and ClinicalTrial.gov. A total of 27 articles fulfilling our inclusion criteria were found and analyzed.Results: There were 21 case reports, four case series and two randomized controlled trials (RCTs) on the biologic TNF-alpha inhibitors for SJS-TEN therapy, comprising 91 patients. TNF-alpha inhibitors were used as monotherapy, second-line therapy or combination therapy. Among them, 79 patients (86.8%) responded well and discharged with few side effects and complications.Conclusions: Biologic TNF-alpha inhibitors are a safe and effective treatment for SJS-TEN. But further, larger RCTs need to be conducted to provide more evidence for clinical application.
- Published
- 2019
28. Histopathological diagnosis of persistent pruritic eruptions associated with adult-onset Still's disease
- Author
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Sha Zhou, Yanyan Wu, Yunlei Pan, Ruzeng Xue, Shunli Tang, Juan Bai, Su Wang, Xiuming Zhang, Hong Fang, Tingting Qu, Jianjun Qiao, Qingmiao Sun, Chuanyin Sun, Sheng Li, and Yinhua Wu
- Subjects
0301 basic medicine ,Adult ,Keratinocytes ,Male ,Adult-onset Still's disease ,medicine.medical_specialty ,Histology ,Neutrophils ,Biopsy ,Dermatomyositis ,Pathology and Forensic Medicine ,Diagnosis, Differential ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Dermis ,medicine ,Humans ,Lupus Erythematosus, Systemic ,In patient ,Lymphocytes ,Aged ,Retrospective Studies ,Skin ,Epidermis (botany) ,business.industry ,Pruritus ,General Medicine ,Exanthema ,Middle Aged ,medicine.disease ,Dermatology ,Rash ,Dyskeratosis ,Drug eruption ,030104 developmental biology ,medicine.anatomical_structure ,Early Diagnosis ,030220 oncology & carcinogenesis ,Female ,Drug Eruptions ,medicine.symptom ,Atrophy ,business ,Still's Disease, Adult-Onset - Abstract
Aims Persistent pruritic eruptions (PPEs), presenting with dyskeratotic keratinocytes histologically, are characteristic skin rash in patients with adult-onset Still's disease (AOSD). The lesions may be histologically similar to other entities that present with dyskeratosis. In the present study, we compared the histopathological features between PPEs and other entities presenting with dyskeratosis. Methods and results To investigate whether histopathological findings can be used to discriminate among PPEs and other entities presenting with dyskeratotic keratinocytes, cutaneous histopathological changes of PPEs associated with AOSD (n = 26) were compared with those of systemic lupus erythematosus (SLE) (n = 16), dermatomyositis (n = 19), and drug eruption (n = 16). Dyskeratosis was observed in the upper one-third of the epidermal layer in all 26 PPEs. The rate of dyskeratosis for PPEs was higher than that for SLE (18.8%) and dermatomyositis (15.8%). In drug eruptions, the dyskeratotic cells were distributed in all levels of the epidermis. Variable densities of neutrophils were found in the dermis in all PPEs. Conclusions Although this was a retrospective study conducted at a single centre, presentation of dyskeratotic keratinocytes in the upper one-third of the epidermal layer is a distinctive histopathological reactive pattern of PPEs. This pattern may be a useful histopathological marker for early diagnosis of AOSD.
- Published
- 2018
29. A genome-wide assessment of rare copy number variants in colorectal cancer
- Author
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Shunli Tang, Shuai Zhang, Xiaoyang Yin, Qiaonan Shan, Yongyong Shi, Dan Yu, Dandan Zhang, Yimin Zhu, Zhenli Li, Meifu Gan, and Maode Lai
- Subjects
Male ,medicine.medical_specialty ,Heredity ,DNA Copy Number Variations ,Nucleosome assembly ,colorectal cancer ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,nucleosome assembly ,Risk Factors ,Missing heritability problem ,mental disorders ,Databases, Genetic ,Epidemiology ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,rare CNVs ,Aged ,Oligonucleotide Array Sequence Analysis ,Genetics ,Gene Expression Profiling ,Age Factors ,Case-control study ,Computational Biology ,Reproducibility of Results ,food and beverages ,Middle Aged ,Heritability ,Phenotype ,Oncology ,Case-Control Studies ,Female ,genome-wide scan ,Colorectal Neoplasms ,Research Paper ,Genome-Wide Association Study - Abstract
// Zhenli Li 1, 2 , Dan Yu 1, 2 , Meifu Gan 3 , Qiaonan Shan 4 , Xiaoyang Yin 4 , Shunli Tang 4 , Shuai Zhang 1, 2 , Yongyong Shi 5 , Yimin Zhu 6 , Maode Lai 1, 2 , Dandan Zhang 1, 2 1 Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China 2 Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China 3 Department of Pathology, Taizhou Hospital, Linhai, Zhejiang, 317000, China 4 Zhejiang University School of Clinical Medicine, Hangzhou, Zhejiang, 310058, China 5 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200000, China 6 Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, 310058, China Correspondence to: Dandan Zhang, e-mail: dandanz@zju.edu.cn Maode Lai, e-mail: lmp@zju.edu.cn Keywords: colorectal cancer, rare CNVs, genome-wide scan, nucleosome assembly Received: April 03, 2015 Accepted: July 06, 2015 Published: July 20, 2015 ABSTRACT Colorectal cancer (CRC) is a complex disease with an estimated heritability of approximately 35%. However, known CRC-related common single nucleotide polymorphisms (SNPs) can only explain ~0.65% of the heritability. This “missing heritability” may be explained partially by rare copy number variants (CNVs). In this study, we performed a genome-wide scan using Illumina Human-Omni Express BeadChip, 694 sporadic CRC cases and 1641 controls were eventually included in our analysis after quality control. The global burden analysis revealed a 1.53-fold excess of rare CNVs in CRC cases compared with controls ( P < 1 × 10 −6 ), and the difference being more pronounced for genic rare CNVs and CNVs overlapped with coding regions (1.65-fold and 1.84-fold, respectively, both P < 1 × 10 −6 ). Interestingly, both the cases in the lowest and middle tertile of age carried a higher burden of rare CNVs comparing to the highest tertile. Furthermore, 639 CNV-disrupted genes exclusive to CRC cases were found to be significantly enriched in gene ontology (GO) terms concerning nucleosome assembly and olfactory receptor activity. Our study was the first to evaluate the burden of rare CNVs in sporadic CRC and suggested that rare CNVs contributed to the missing heritability of CRC.
- Published
- 2015
30. Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients
- Author
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Xiaoyang Yin, Zhenli Li, Dandan Zhang, Dan Yu, Ledong Wan, Maode Lai, Yimin Zhu, Shuai Zhang, Yiping Tian, Meifu Gan, Shunli Tang, and Hanyun Zhang
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Colorectal cancer ,Value (computer science) ,Kaplan-Meier Estimate ,Statistical significance ,Internal medicine ,Dual-specificity phosphatase ,Gene expression ,Biomarkers, Tumor ,Medicine ,Humans ,RNA, Messenger ,Pathological ,Survival analysis ,Aged ,Neoplasm Staging ,biology ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Lymphatic Metastasis ,biology.protein ,Dual-Specificity Phosphatases ,Mitogen-Activated Protein Kinase Phosphatases ,Female ,business ,Colorectal Neoplasms - Abstract
Dual specificity phosphatase 22 (DUSP22) is a novel dual specificity phosphatase that has been demonstrated to be a cancer suppressor gene associated with numerous biological and pathological processes. However, little is known of DUSP22 expression profiling in colorectal cancer and its prognostic value. Our study aims to investigate the role of DUSP22 expression in the prognosis of colorectal cancer. We detected the mRNA expression in 92 paired primary colorectal cancer tissues and the corresponding adjacent normal tissues by using QuantiGenePlex assay. The Friedman test was used to determine the statistical difference of gene expression. Kaplan-Meier survival analysis was performed. Mann-Whitney test and Kruskal-Wallis test were used to conduct data analyses to determine the prognostic value. Statistical significance was set at P 0.05. In 74 of 92 cases, DUSP22 mRNA was reduced in primary colorectal cancer tissues, compared to the adjacent normal tissues. The mRNA levels of DUSP22 were significantly lower in colorectal cancer tissues than in adjacent normal tissues (0.0290 vs. 0.0658; P 0.001). Low expression of DUSP22 correlated significantly with large tumor size (P = 0.013). No association was observed between DUSP22 mRNA expression and differentiation, histopathological type, tumor invasion, lymph node metastases, metastases, TNM stage, and Duke's phase (all P 0.05). Kaplan-Meier analysis indicated that DUSP22 expression had no significant relationship with overall survival in all patients (P 0.05). Interestingly, low expression level of DUSP22 in stage IV patients had a poor survival measures with a marginal P value (P = 0.07). Reduced DUSP22 expression was found in colorectal cancer specimens. Low expression level of DUSP22 in stage IV patients had a poor survival outcome. Further study is required for the investigation of the role of DUSP22 in colorectal cancer.
- Published
- 2015
31. Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome.
- Author
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Dandan Zhang, Zhenli Li, Xiaohong Xu, Dan Zhou, Shunli Tang, Xiaoyang Yin, Fangying Xu, Hui Li, Yuan Zhou, Tao Zhu, Hong Deng, Shuai Zhang, Qiong Huang, Jing Wang, Wei Yin, Yimin Zhu, and Maode Lai
- Subjects
COLON cancer ,DNA copy number variations ,LOCUS (Genetics) ,BIG data ,MICRODISSECTION ,TUMORS - Abstract
Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10
-5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17-0.62, 0.12-0.57 and 0.37-0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
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