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Psoriasis: HELP
Articles from Liaoning Province
Based on 45 articles published since 2009
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These are the 45 published articles about Psoriasis that originated from Liaoning Province during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Oxidative stress in psoriasis and potential therapeutic use of antioxidants. 2016

Lin, Xiran / Huang, Tian. ·a Department of Dermatology , The First Affiliated Hospital of Dalian Medical University , Dalian , China ; · b Department of Dermatology , The Second Affiliated Hospital of Dalian Medical University , Dalian , China. ·Free Radic Res · Pubmed #27098416.

ABSTRACT: The pathophysiology of psoriasis is complex and dynamic. Recently, the involvement of oxidative stress in the pathogenesis of psoriasis has been proposed. Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage. In this article, the published studies on the role of oxidative stress in psoriasis pathogenesis are reviewed, focusing on the impacts of oxidative stress on dendritic cells, T lymphocytes, and keratinocytes, on angiogenesis and on inflammatory signaling (mitogen-activated protein kinase, nuclear factor-κB, and Janus kinase/signal transducer and activator of transcription). As there is compelling evidence that oxidative stress is involved in the pathogenesis of psoriasis, the possibility of using this information to develop novel strategies for treatment of patients with psoriasis is of considerable interest. In this article, we also review the published studies on treating psoriasis with antioxidants and drugs with antioxidant activity.

2 Review Impact of pregnancy and oestrogen on psoriasis and potential therapeutic use of selective oestrogen receptor modulators for psoriasis. 2016

Lin, X / Huang, T. ·Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian, China. · Department of Dermatology, Second Affiliated Hospital of Dalian Medical University, Dalian, China. ·J Eur Acad Dermatol Venereol · Pubmed #27072912.

ABSTRACT: Majority of female patients show improvement of psoriasis during pregnancy. This is demonstrated to be correlated with high levels of oestrogen. Even in male patient, oestrogen level is inversely correlated with the severity of psoriasis. However, a minority of female psoriatic patients still experience worsening during pregnancy. Oestrogen might improve psoriasis by suppressing the T-cell immune response, reducing the keratinocyte (KC) cytokine and chemokine production, restoring the balance of redox and enhancing the skin barrier. However, it might worsen the disease by stimulating KC proliferation and promoting angiogenesis. This complex role of oestrogen in the pathogenesis of psoriasis might explain why the two opposite effects of pregnancy coexist. Data shows that the number of improving patients with psoriasis in pregnancy is double the number of the worsening patients, suggesting that oestrogen may be potentially useful in the treatment of psoriasis. However, oestrogen is not considered suitable as a long-term treatment subject to negative side-effects. This review discusses current studies on taking selective oestrogen receptor mediators as a novel potential therapeutic option for psoriasis.

3 Review Topical calcipotriol/betamethasone dipropionate for psoriasis vulgaris: A systematic review. 2016

Yan, Ru / Jiang, Shibin / Wu, Yan / Gao, Xing-Hua / Chen, Hong-Duo. ·Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China. ·Indian J Dermatol Venereol Leprol · Pubmed #26924402.

ABSTRACT: Topical calcipotriol/betamethasone dipropionate ointment/gel has been commonly used for the treatment of psoriasis vulgaris. However, the efficacy of this combination needs to be consolidated. We aimed to assess the effects and safety profile of calcipotriol/betamethasone dipropionate for the treatment of psoriasis vulgaris, using evidence based approach. Randomized controlled trials on the treatment of psoriasis vulgaris with calcipotriol/betamethasone dipropionate were identified by searching PubMed, China National Knowledge Infrastructure and the Cochrane Library. The primary outcome measure was the Psoriasis Area and Severity Index (PASI) score. Ten randomized controlled trials involving 6590 participants were included. The methodologies of the studies were generally of moderate to high quality. These trials used topical calcipotriol/betamethasone dipropionate for 4 or 8 weeks, and were compared with topical calcipotriol or betamethasone. The results showed that calcipotriol/betamethasone dipropionate was more effective than controls. A four-week treatment with calcipotriol/betamethasone dipropionate did not show any significant difference between the once-daily or twice-daily regimen. The adverse events of calcipotriol/betamethasone dipropionate were tolerable and acceptable. The reports included in this review are heterogenous and have limitations. Topical application of calcipotriol/betamethasone dipropionate once daily is an efficacious treatment for psoriasis vulgaris and is associated with few side effects.

4 Review Co-signaling molecules in psoriasis pathogenesis: implications for targeted therapy. 2015

Lin, Xiran / Huang, Tian. ·Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, 222 Zhong Shan Lu, Dalian 116011, China. Electronic address: lxiran02@aliyun.com. · Department of Dermatology, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Lu, Dalian 116027, China. ·Hum Immunol · Pubmed #25636578.

ABSTRACT: Psoriasis is a T cell-dependent immune-mediated disease of the skin and joints. It is clear that co-stimulatory and co-inhibitory molecules (currently named co-signaling molecules collectively) synergize with TCR signaling to promote or inhibit T cell activation and function. In recent years, enthusiasm in the field of co-signaling research has been fueled by the success of co-stimulatory and co-inhibitory immunotherapy for the treatment of human diseases. This review outlines the involvement of several sets of co-signaling molecules in the immunopathogenesis of psoriasis. We then describe the relevant preclinical studies and summarize recent clinical findings on targeting these molecules for the treatment of psoriasis.

5 Review Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target? 2014

Huang, Tian / Lin, Xiran / Meng, Xianmin / Lin, Mao. ·Department of Dermatology, The Second Affiliated Hospital of Dalian Medical University, 476 Zhong Shan Lu, Dalian 116027, China. hyshi2010@yahoo.com. ·Acta Derm Venereol · Pubmed #24217655.

ABSTRACT: Psoriasis is a common chronic inflammatory disease of the skin. Its pathogenesis has not been completely elucidated. Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway has been identified as a key signaling pathway for important cellular functions. The data collected in this review suggest that overexpression of the PI3K/Akt/mTOR pathway may play an important role in the pathogenesis of psoriasis by mediating the immune-pathogenesis, the epidermal hyperplasia or/and the angiogenesis in the disease. Advances in understanding the pathogenesis of psoriasis has provided new insight into potential therapeutic targets, including the development of biological therapies, resulting in remarkable clinical responses in patients with severe psoriasis. More recently, small molecule oral preparations targeting intracellular signaling that may prove effective have been developed. Data suggest that PI3K/Akt/mTOR pathway may be a potential target for treatment of psoriasis.

6 Review Treatment of psoriasis with interleukin-12/23 monoclonal antibody: a systematic review. 2012

Wu, Yan / Chen, Jing / Li, Yuan-Hong / Ma, Guo-Zhang / Chen, John Z S / Gao, Xing-Hua / Chen, Hong-Duo. ·Department of Dermatology, No.1 Hospital of China Medical University, 155N.Nanjing Street, Shenyang 110001 P.R.China. ·Eur J Dermatol · Pubmed #22266126.

ABSTRACT: OBJECTIVE: To systematically review the efficacy and safety of interleukin-12/23 monoclonal antibody (IL-12/23 mAb) on psoriasis. METHODS: Relevant randomized controlled trials (RCTs) were identified by systematic literature searches in MEDLINE, OVID, EMBASE, Cochrane Library, and the metaRegister of Controlled Trials. The efficacy outcomes and adverse effects of included RCTs were critically assessed. RESULTS: A total of 3365 participants in 5 multicenter RCTs were included. The RRs of most efficacy outcomes showed significant differences between i) IL-12/23 mAb and placebo at week 12/16; ii) IL-12/23 mAb and etanercept at week 12; iii) IL-12/23 mAb in high dose and IL-12/23 mAb in low dose at week 24/28. Increasing treatment times did not obviously provide additional benefit to efficacy improvement. The adverse events of IL-12/23 mAb were similar to those of controls. Antibodies to IL-12/23 mAb were mostly undetected or shown at low titer. Treatment with IL-12/23 mAb did not influence related biochemical markers. CONCLUSIONS: IL-12/23 mAb was effective in the treatment of psoriasis on skin lesions, health-related quality of life and psoriatic arthritis in the short-term. The increase in treatment time points was not associated with additional efficacy and dose-dependence was observed with the ongoing treatment up to week 24/28. The adverse effects were minimal and tolerable.

7 Clinical Trial The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: A Phase 3, randomized, double-blind, placebo-controlled study. 2017

Zhang, JianZhong / Tsai, Tsen-Fang / Lee, Min-Geol / Zheng, Min / Wang, Gang / Jin, HongZhong / Gu, Jun / Li, RuoYu / Liu, QuanZhong / Chen, Jin / Tu, CaiXia / Qi, ChunMei / Zhu, Hua / Ports, William C / Crook, Tim. ·Peking University People's Hospital, Department of Dermatology, Beijing, China. Electronic address: rmzjz@126.com. · National Taiwan University Hospital, Department of Dermatology, Taipei, Taiwan. Electronic address: tftsai@yahoo.com. · Yonsei University College of Medicine, Department of Dermatology, Seoul, Republic of Korea. Electronic address: mglee@yuhs.ac. · Second Affiliated Hospital School of Medicine, Zhejiang University, Department of Dermatology, Hangzhou, Zhejiang, China. Electronic address: minz@zju.edu.cn. · Xijing Hospital, The Fourth Military Medical University, Department of Dermatology, Xi'an, Shaanxi, China. Electronic address: xjpfwanggang@163.com. · Peking Union Medical College Hospital, Department of Dermatology, Beijing, China. Electronic address: jinhongzhong@263.net. · Changhai Hospital, The Second Military Medical University, Department of Dermatology, Shanghai, China. Electronic address: gujun79@163.com. · Peking University First Hospital, Department of Dermatology, Beijing, China. Electronic address: mycolab@126.com. · Tianjin Medical University General Hospital, Department of Dermatology, Tianjin, China. Electronic address: liuquanzhong@medmail.com.cn. · Sichuan Provincial People's Hospital, Institute of Dermatology, Chengdu, Sichuan, China. Electronic address: chenjin99114@sina.com. · The Second Affiliated Hospital of Dalian Medical University, Department of Dermatology, Dalian, Liaoning, China. Electronic address: tucx2003@163.com. · Development China, GPD, Pfizer Investment Co. Ltd., Beijing, China. Electronic address: ChunMei.Qi@Pfizer.com. · Pfizer Development China, Shanghai, China. Electronic address: hua.zhu@pfizer.com. · Pfizer Inc., Groton, CT, USA. Electronic address: william.c.ports@pfizer.com. · Pfizer Ltd., Tadworth, United Kingdom. Electronic address: Tim.Crook@pfizer.com. ·J Dermatol Sci · Pubmed #28558978.

ABSTRACT: BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. OBJECTIVE: This study assessed tofacitinib efficacy and safety vs placebo in Asian patients with moderate to severe chronic plaque psoriasis. METHODS: Patients from China mainland, Taiwan, and Korea were randomized 2:2:1:1 to tofacitinib 5mg (N=88), tofacitinib 10mg (N=90), placebo→5mg (N=44), or placebo→10mg (N=44), twice daily (BID) for 52 weeks. Placebo-treated patients advanced to tofacitinib at Week 16. Co-primary efficacy endpoints: proportions of patients achieving Physician's Global Assessment (PGA) response ('clear' or 'almost clear') and proportion achieving ≥75% reduction from baseline Psoriasis Area and Severity Index (PASI75) at Week 16. RESULTS: At Week 16, more patients achieved PGA and PASI75 responses with tofacitinib 5mg (52.3%; 54.6%) and 10mg (75.6%; 81.1%) BID vs placebo (19.3%; 12.5%; all p<0.0001). Of patients with a Week 16 response, 73.6% and 75.0% maintained PGA response, and 76.8% and 84.9% maintained PASI75 to Week 52 with tofacitinib 5mg and 10mg BID, respectively. Over 52 weeks, 2.2-4.5% of patients across treatment groups experienced serious adverse events, and 1.1-6.8% discontinued due to adverse events. CONCLUSION: Tofacitinib demonstrated efficacy vs placebo at Week 16 in Asian patients with moderate to severe plaque psoriasis; efficacy was maintained through Week 52. No unexpected safety findings were observed. [NCT01815424].

8 Clinical Trial Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study. 2017

Cai, L / Gu, J / Zheng, J / Zheng, M / Wang, G / Xi, L-Y / Hao, F / Liu, X-M / Sun, Q-N / Wang, Y / Lai, W / Fang, H / Tu, Y-T / Sun, Q / Chen, J / Gao, X-H / Gu, Y / Teixeira, H D / Zhang, J-Z / Okun, M M. ·Peking University People's Hospital, Beijing, China. · Shanghai Changhai Hospital, Shanghai, China. · Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, China. · The first Affiliated Hospital of Fourth Military Medical University, PLA (Xijing Hospital), Xi'an, China. · Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. · The First Affiliated Hospital of Third Military Medical University, PLA (Southwest Hospital), Chongqing, China. · First Affiliated Hospital of Dalian Medical University, Dalian, China. · Peking Union Medical College Hospital, Beijing, China. · Peking University First Hospital, Beijing, China. · The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. · The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China. · Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China. · Qilu Hospital of Shandong University, Jinan, China. · Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China. · The First Hospital of China Medical University, Shenyang, China. · AbbVie Inc., North Chicago, IL, USA. · Fort HealthCare, Fort Atkinson, WI, USA. ·J Eur Acad Dermatol Venereol · Pubmed #27504914.

ABSTRACT: BACKGROUND: This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF-α inhibitor, adalimumab, for Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In the 12-week, double-blind, placebo-controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every-other-week (following a single 80 mg dose), or placebo every-other-week. In the subsequent 12-week, open-label, Period B, all patients received adalimumab 40 mg every-other-week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug. RESULTS: For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All-adalimumab Population), treatment-emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All-adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure). CONCLUSION: In these Chinese patients with moderate-to-severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.

9 Article A Novel Surfactant-Free O/O Paclitaxel Ointment for the Topical Treatment of Psoriasis. 2019

Yin, Xiaozhuo / Cao, Xiaolei / Li, Jiaqi / Cheng, Xu / Cheng, Gang / Zou, Meijuan / Piao, Hongyu. ·Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China. · Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China. Hy_piao@126.com. ·AAPS PharmSciTech · Pubmed #31165303.

ABSTRACT: Psoriasis is an autoimmune disorder disease with pink-colored plaques and excessive proliferation which is hard to be cured completely. The study focuses on the anti-psoriatic efficacy of O/O paclitaxel ointment which can promote the assembly of microtubules and lead to death of overproliferation cells of the psoriasis epidermal. A high-speed shearing method was adopted in preparing the ointment, in which propylene carbonate was used as the internal oil phase to solve paclitaxel completely. It was characterized by the appearance, particle size, rheological behavior, and in vitro release. The amount of paclitaxel retained in normal skin and psoriatic skin was 1.00 ± 0.50 versus 1.53 ± 0.48 μg/g for 0.03% PTX ointment, 1.30 ± 0.39 versus 2.77 ± 0.49 μg/g for 0.1% PTX ointment, and 2.22 ± 0.92 versus 6.65 ± 0.87 μg/g for 0.3% PTX ointment, respectively, which implied that paclitaxel could better retain in inflamed skin than in normal skin; also the amount of drug retained in the skin was proportional to drug content. Paclitaxel ointment displayed good topical tolerance after repeated application on normal mice skin. The therapeutic efficacy of paclitaxel ointment was evaluated with an imiquimod-induced psoriatic model. A significant improvement has been shown both in the phenotypic and histopathological features of psoriatic skin treated with the ointment. There was also a significant reduction in the epidermal thickness compared to the imiquimod group. The findings confirm that the O/O PTX ointment without any surfactant appears to be a promising approach for the treatment of psoriasis.

10 Article Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis. 2019

Niu, Xue-Li / Huang, Yu / Gao, Ya-Li / Sun, Yu-Zhe / Han, Yang / Chen, Hong-Duo / Gao, Xing-Hua / Qi, Rui-Qun. ·Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China. · NHC Key Laboratory of Immunodermatology, China Medical University, Shenyang, Liaoning 110001, China. · Key Laboratory of Immunodermatology, Ministry of Education, Shenyang, Liaoning 110001, China. · Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110001, China. ·Chin Med J (Engl) · Pubmed #30741833.

ABSTRACT: BACKGROUND: As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis. METHODS: WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC). RESULTS: Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased. CONCLUSIONS: IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.

11 Article Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris. 2019

Kuang, Ye Hong / Lu, Yan / Yan, Ke Xiang / Liu, Pan Pan / Chen, Wang Qing / Shen, Min Xue / He, Yi Jing / Wu, Li Sha / Qin, Qun Shi / Zhou, Xing Chen / Li, Jie / Su, Juan / zhiLv, Cheng / Zhu, Wu / Chen, Xiang. ·Department of Dermatology, XiangYa Hospital, Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, Hunan, China. · Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China. · Institute of medical science, Xiangya Hospital, Central South University, Changsha, Hunan, China. · Clinical Centre for Psoriasis, Dalian Skin Diseases Hospital, Dalian, Liaoning, China. · Department of Dermatology, XiangYa Hospital, Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, Hunan, China. Electronic address: zhuwu70@hotmail.com. · Department of Dermatology, XiangYa Hospital, Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, Hunan, China. Electronic address: chenxck@126.com. ·J Dermatol Sci · Pubmed #30563733.

ABSTRACT: BACKGROUND: Methotrexate is the first systemic therapeutics of psoriasis. It is reported that 40% of the patients achieved a PASI75 after 12 weeks with a small dose of methotrexate (15mg / w) treatment. So far there is not any large-scale exome sequencing been used to predict the efficacy of methotrexate in the treatment of psoriasis vulgaris. OBJECTIVE: To analyze the genetic polymorphism to predict methotrexate efficacy in Chinese patients with psoriasis vulgaris. METHODS: In this study, we used the whole exon high-throughput sequencing technology to detect the DNA sequence of 22 psoriasis vulgaris patients (11 responders, 11 non-responders) treated with methotrexate and captured approximately 236 variants with statistically significant in the whole exon sequencing, then in accordance with statistical differences and clinical relevance, we further selected 36 SNPs and 14 SNPs that have been reported in articles associated with the response of methotrexate. We used MassARRAY method to verify the 50 SNPs in 100 psoriatic patients treated with methotrexate. RESULTS: We found 3 SNPs, rs216195T>C in SMG6, rs1050301G>A in IMMT, rs2285421T>C in UPK1A which might associate with the drug response of methotrexate. CONCLUSION: We have searched 3 new SNPs that could predict the efficacy of methotrexate in psoriasis vulgaris to some extent, providing a theoretical basis for precision medicine of methotrexate in future.

12 Article Comparison of normal versus imiquimod-induced psoriatic skin in mice for penetration of drugs and nanoparticles. 2018

Sun, Lin / Liu, Zeyu / Lin, Zibei / Cun, Dongmei / Tong, Henry Hy / Yan, Ru / Wang, Ruibing / Zheng, Ying. ·State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region, People's Republic of China, yzheng@umac.mo. · Department of Pharmaceutical Sciences, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, 519041, People's Republic of China. · Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, People's Republic of China. · School of Health Sciences, Macao Polytechnic Institute, Macao Special Administrative Region, People's Republic of China. ·Int J Nanomedicine · Pubmed #30271151.

ABSTRACT: Background: As an immune-mediated skin disease, psoriasis encounters therapeutic challenges on topical drug development due to the unclear mechanism, and complicated morphological and physiological changes in the skin. Methods: In this study, imiquimod-induced psoriatic mouse skin (IMQ-psoriatic skin) was chosen as the in vitro pathological model to explore the penetration behaviors of drugs and nanoparticles (NPs). Results: Compared with normal skin, significantly higher penetration and skin accumulation were observed in IMQ-psoriatic skin for all the three model drugs. When poorly water-soluble curcumin was formulated as NPs that were subsequently loaded in gel, the drug's penetration and accumulation in both normal and IMQ-psoriatic skins were significantly improved, in comparison with that of the curcumin suspension. Interestingly, the NPs' size effect, in terms of their penetration and accumulation behaviors, was more pronounced for IMQ-psoriatic skin. Furthermore, by taking three sized FluoSpheres Conclusion: In conclusion, the alternation of the IMQ-psoriatic skin structure will lead to the enhanced penetration of drug and NPs, and should be considered in topical drug formulation and further clinical practice for psoriasis therapy.

13 Article Efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment in the treatment of mild to moderate psoriasis vulgaris: A randomized, single-blind, multicenter clinical trial. 2018

Xia, Lixin / Li, Ruoyu / Wang, Yun / Lin, Zhimiao / Zheng, Jie / Li, Xia / Lu, Qianjin / Zhang, Jing / Jin, Hongzhong / Fu, Lanqin / Zhang, Xibao / Liu, Yumei / Yang, Sen / Xiao, Fengli / Gao, Xing-Hua. ·Department of Dermatology of The First Hospital of China Medical University, Shenyang, Liaoning, China. · Department of Dermatology of Peking University First Hospital, Beijing, China. · Department of Dermatology of RuiJin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Department of Dermatology of The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. · Department of Dermatology of Peking Union Medical College Hospital, Beijing, China. · Department of Dermatology of Guangzhou Institute of Dermatology, Guangzhou, Guangdong, China. · Department of Dermatology of The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui. ·Dermatol Ther · Pubmed #30253049.

ABSTRACT: To assess the efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment and calcipotriol/betamethasone dipropionate ointment in the treatment of mild-to-moderate patients with psoriasis vulgaris. This was a randomized, single-blind, multicenter clinical trial. A total of 240 patients were randomized to receive twice-daily all-trans retinoic acid/Clobetasol Propionate Compound Ointment (treatment group) or once-daily calcipotriol/betamethasone dipropionate ointment (control group) for 4 weeks. The efficacy, safety, and cost-effectiveness were assessed at Weeks 2 and 4. After 4 weeks, both groups showed a significant clinical improvement compared to baseline (88.33% vs. 89.83%, respectively, p = .7112). But PASI 75 response in the treatment group was superior to the control group (44.12% vs. 28.57%, respectively, p = .0200), at Week 4. SSRI improvement rate in the treatment group was also superior to control group (67.11% vs. 59.43%, respectively, p = .0119) at Week 4. All-trans retinoic acid/Clobetasol Propionate Compound Ointment showed a significant clinical improvement in erythema, infiltration, and scales of skin lesions and PASI score compared to baseline. 1.67% of patients (treatment group) reported adverse reactions compared to 2.50% (control group) with no statistical significance. In addition, the cost-effectiveness assessment showed a higher cost-effectiveness of the treatment group compared to the control group in 4 weeks (199.25 vs. 801.51). All-trans retinoic acid/Clobetasol Propionate Compound Ointment was effective and safe in the treatment of psoriasis vulgaris with similar efficacy as calcipotriol/betamethasone dipropionate ointment and lower treatment costs.

14 Article Decryption of Active Constituents and Action Mechanism of the Traditional Uighur Prescription (BXXTR) Alleviating IMQ-Induced Psoriasis-Like Skin Inflammation in BALB/c Mice. 2018

Pang, Xiaobo / Zhang, Ke / Huang, Jian / Wang, Hangyu / Gao, Le / Wang, Tao / Sun, Yingnan / Chen, Long / Wang, Jinhui. ·School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. pangxiaobo126@126.com. · School of Pharmacy, Shihezi University (Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education), Shihezi 832001, China. xjzk1984@163.com. · School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. 13504051049@163.com. · Department of Medicinal Chemistry and Natural Medicine Chemistry (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin 150081, China. 13504051049@163.com. · School of Pharmacy, Shihezi University (Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education), Shihezi 832001, China. 18909932852@189.com. · School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. 13940164780@163.com. · School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. WangTao9492@163.com. · School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. 17614665295@163.com. · School of Pharmacy, Shihezi University (Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education), Shihezi 832001, China. xiaochenlong2@126.com. · School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. 15999290001@163.com. · School of Pharmacy, Shihezi University (Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education), Shihezi 832001, China. 15999290001@163.com. · Department of Medicinal Chemistry and Natural Medicine Chemistry (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin 150081, China. 15999290001@163.com. ·Int J Mol Sci · Pubmed #29933541.

ABSTRACT: Bai Xuan Xia Ta Re Pian (BXXTR) is a traditional Uighur medicine ancient prescription in China widely used in the treatment of psoriasis, presenting a high curative rate and few side effects. Given that the active constituents and action mechanism still remain unclear, the aim of this study is to explore the potential active constituents and mechanism of antipsoriasis of BXXTR. Psoriasis-like lesions model in BALB/c mice was induced by Imiquimod (IMQ), including five treatment groups: control group, IMQ-treated group, IMQ-ACITRETIN group (Positive control group), IMQ-BXXTR low dose group, IMQ-BXXTR medium dose group and IMQ-BXXTR high dose group. The Psoriasis Area and Severity Index (PASI) score, skin and ear thickness, and histologic section were collected. The differentially expressed genes were determined by using RNAseq technology and the relevant pathways were analyzed by KEGG database. The ELISA kit and western blot assays were used to detect the related protein expression levels. In addition, the chemical constituents of BXXTR were determined by UPLC-TOF-MS analysis and the potential active constituents were predicted by SEA DOCK and Gene Ontology (GO). The data demonstrated that BXXTR significantly alleviated IMQ-induced psoriasis. RNA-seq analysis showed that BXXTR induced the expression levels of 31 genes; the KEGG analysis suggested that BXXTR could significantly change IL-17-related inflammatory pathways. The ELISA kit confirmed that the expression level of IL-17A protein was significantly reduced. 75 compounds of BXXTR were determined by UPLC-TOF-MS analysis, 11 of 75 compounds were identified as potential active compounds by similarity ensemble approach docking (SEA DOCK) and Gene Ontology (GO). BXXTR reduced the severity of skin lesions by inhibiting IL-17-related inflammatory pathways. The results indicated that BXXTR could suppress psoriasis inflammation by multiple-constituents-regulated multiple targets synergistically. Collectively, this study could provide important guidance for the elucidation of the active constituents and action mechanism of BXXTR for the treatment of psoriasis.

15 Article Effect of γ-secretase inhibitor on Th17 cell differentiation and function of mouse psoriasis-like skin inflammation. 2018

Ma, Lei / Xue, Haibo / Qi, Ruiqun / Wang, Yanqin / Yuan, Libing. ·Department of Dermatology, Binzhou Medical University Hospital, 661 Second Huanghe Road, Binzhou, 256603, China. doctor_malei@hotmail.com. · Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, 661 Second Huanghe Road, Binzhou, 256603, China. xue_haibo@hotmail.com. · Department of Dermatology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Road, Shenyang, 110001, China. · Department of Dermatology, Binzhou Medical University Hospital, 661 Second Huanghe Road, Binzhou, 256603, China. · Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, 661 Second Huanghe Road, Binzhou, 256603, China. ·J Transl Med · Pubmed #29523162.

ABSTRACT: BACKGROUND: Th17 cells and its effective cytokine IL-17A play an important role in the pathogenesis of abnormal immune responses in psoriasis. Notch1 signaling has been implicated in Th17 cell differentiation and function. In this study, our aim was to evaluate the possible inhibitory effect of Notch1 signaling inhibitor, γ-secretase inhibitor DAPT, on psoriatic Th17 cell differentiation and function in a mouse model of psoriasis-like skin inflammation. METHODS: Mouse psoriasis-like skin inflammation model was established by topical 5% imiquimod (IMQ) application, and experimental mice were divided into control group, IMQ-treated group and IM + DAPT-treated group. DAPT and the equivalent amount of Dimethyl sulfoxide was intraperitoneally injected in IMQ + DAPT-treated group and the other two experimental groups respectively. Skin tissues of the three experimental groups were acquired and stained with haematoxylin and eosin (HE). Splenic single-cells and serum were collected to detect the percentage of Th17 cells, the mRNA expression levels of Notch1 and its target gene Hes-1, Th17-specific transcription factor RORγt and its effective cytokines IL-17A, as well as IL-17A serum concentration. In addition, splenic CD4 RESULTS: DAPT treatment alleviated the severity of IMQ-induced mouse psoriasis-like skin inflammation and decreased the scores of erythema, scaling and thickening. HE stain reveals obviously reduced epidermal hyperplasia and dermal inflammatory cells infiltration in IMQ + DAPT-treated mice. The increased expression of splenic Th17 cell percentage, along with Notch1, Hes-1, RORγt and IL-17A mRNA and IL-17A serum concentration in IMQ-treated mice were significantly decreased when experimental mice were treated by IMQ and DAPT combinedly. Data obtained from in vitro study in IMQ-treated mice also demonstrated that blocking Notch1 signaling by DAPT can result in a dose-dependent decrease of Th17 cell proportion, mRNA expression of Notch1, Hes-1, RORγt and IL-17A as well as IL-17A secretion in splenic CD4 CONCLUSION: These data suggest that Notch1 inhibition by DAPT can effectively alleviate the severity of mouse psoriasis-like skin inflammation by regulating the differentiation and function of Th17 cells, indicating that DAPT might be a potential therapeutic candidate for the treatment of psoriatic inflammation.

16 Article IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis. 2018

Hou, Yuzhu / Zhu, Linnan / Tian, Hongling / Sun, Hai-Xi / Wang, Ruoyu / Zhang, Lianfeng / Zhao, Yong. ·State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China. · Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China. wry1963@sohu.com. · Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. zhanglf@cnilas.org. · State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China. zhaoy@ioz.ac.cn. ·Protein Cell · Pubmed #29508278.

ABSTRACT: Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.

17 Article Dissection of a circulating CD3 2018

Niu, J / Zhai, Z / Hao, F / Zhang, Y / Song, Z / Zhong, H. ·Department of Dermatology, General Hospital of Shenyang Military, Shenyang, Liaoning, China. · Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China. · Department of Zhonghua Clinic in Liangjiang New Area, Chongqing, China. ·Clin Exp Immunol · Pubmed #29377068.

ABSTRACT: CD3

18 Article Efficacy and safety of total glucosides of paeony combined with acitretin in the treatment of moderate-to-severe plaque psoriasis: a double-blind, randomised, placebo-controlled trial. 2017

Yu, Chen / Fan, Xueli / Li, Zhenlu / Liu, Xiaoming / Wang, Gang. ·Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. · Department of Dermatology, Henan Provincial People's Hospital, Henan, China. · Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Liaoning, China. ·Eur J Dermatol · Pubmed #28400341.

ABSTRACT: Although acitretin has been widely used for the treatment of psoriasis, additional safer and more effective approaches, including traditional Chinese medicine, are needed. To investigate the efficacy and safety of total glucosides of paeony (TGP) combined with acitretin in the treatment of moderate-to-severe plaque psoriasis. A randomised, double-blind, placebo-controlled, multi-centre clinical study was conducted. In total, 108 patients with moderate-to-severe plaque psoriasis were randomly assigned to treatment with "TGP plus acitretin" (group A) or "placebo plus acitretin" (group B) for 12 weeks. After 12 weeks of therapy, the percentage of patients achieving a 50% reduction in Psoriasis Area and Severity Index was 90% in group A and 70.5% in group B (p<0.05). The rate of serum alanine aminotransferase elevation was 6.25% in group A and 20.4% in group B (p<0.05). TGP is conducive to enhancing anti-psoriatic efficacy and reducing liver damage due to acitretin. TGP combined with acitretin is a safe and effective treatment approach for moderate-to-severe plaque psoriasis.

19 Article Enhanced topical penetration, system exposure and anti-psoriasis activity of two particle-sized, curcumin-loaded PLGA nanoparticles in hydrogel. 2017

Sun, Lin / Liu, Zeyu / Wang, Lun / Cun, Dongmei / Tong, Henry H Y / Yan, Ru / Chen, Xin / Wang, Ruibing / Zheng, Ying. ·State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. · Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning, China. · School of Health Sciences, Macao Polytechnic Institute, Macao SAR, China. · State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. Electronic address: yzheng@umac.mo. ·J Control Release · Pubmed #28344018.

ABSTRACT: Psoriasis is an immune-mediated skin disorder, which is triggered by the aberrant activation of dendritic cells in skin. This activation is followed by the complex interaction between the immune cells in the skin and keratinocyte in the epidermis. To improve the conditions of poor aqueous solubility and chemical stability, overcome skin barriers, and enhance in vivo anti-psoriatic activity, curcumin (Cur) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were fabricated and administered by topical route to treat imiquimod (IMQ)-induced psoriasis-like mouse model. Spherical Cur-NPs with the mean particle sizes of 50nm and 150nm, respectively, were fabricated using a multi-inlet vortex mixer system, with both exhibiting significantly stronger anti-proliferation effect than Cur solution on HaCaT cells in vitro. Psoriatic skin was utilized in the in vitro skin penetration studies, and the results demonstrated that more drugs penetrated through or accumulated in the skin when administered as the Cur-NPs-loaded hydrogel compared to the drug suspension loaded hydrogel. To compare the nanosizing effect of these Cur-NPs, the mice with IMQ-induced psoriasis-like skin disease were treated with blank gel, Cur gel, 50nm sized NPs gel, 150nm sized NPs gel or tracrolimus cream (positive control), respectively. The results indicated that Cur-NPs hydrogel has a superior performance to Cur hydrogel on the IMQ-induced psoriasis-like mouse model in terms of morphological evaluation, biomarkers at mRNA, and protein levels. In conclusion, encapsulation of Cur into PLGA NPs, particularly for NPs of 50nm, could facilitate lipophilic Cur's dispersion, sustained-release, accumulation, and penetration across the skin and into the blood circulation, which significantly improves anti-psoriasis activity in mice.

20 Article Efficacy and safety of interleukin-17 antagonists in patients with plaque psoriasis: a meta-analysis from phase 3 randomized controlled trials. 2017

Wu, D / Hou, S-Y / Zhao, S / Hou, L-X / Jiao, T / Xu, N-N / Zhang, N. ·Second Departments of Rheumatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. · Intensive Care Unit, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China. ·J Eur Acad Dermatol Venereol · Pubmed #28107570.

ABSTRACT: BACKGROUND: The interleukin-17 (IL-17) cytokine pathway plays a key role in the development of psoriasis. Antibodies targeting IL-17 or blocking its receptor may be a new therapeutic approach for psoriasis. To assist treatment selection in daily practice, it is essential to understand the benefit and risk profile of IL-17 antagonists. OBJECTIVE: We performed a meta-analysis to evaluate the efficacy and safety of IL-17 antagonists in patients with psoriasis. METHODS: We searched a number of databases for relevant randomized controlled trials (RCTs) published before May 2016. The following outcomes were evaluated: Psoriasis Area and Severity Index (PASI) 75, 90, 100 response, Investigator's Global Assessment (IGA) score of 0 or 1 response, adverse events (AEs) and withdrawals. The meta-analysis was performed using Review Manager 5.2 software. RESULTS: Nine RCTs with 5951 patients were included. IL-17 antagonists achieved higher PASI 75, 90, 100 response rates and Dermatology Life Quality Index 0 or 1 response rates than placebo and a lower incidence of discontinuations due to lack of efficacy. In the safety analysis, no significant differences were found between the IL-17 antagonists and placebo in the proportion of patients with serious AEs, cardiovascular disease and discontinuations due to AEs. However, IL-17 antagonists were associated with a higher proportion of patients with any AEs and infections than placebo. CONCLUSION: IL-17 antagonists were effective, with an acceptable safety profile, for patients with plaque psoriasis. Vigilance because of the potential for infection will be necessary for IL-17 antagonists.

21 Article Influence of different types of contact hypersensitivity on imiquimod-induced psoriasis-like inflammation in mice. 2016

Bai, Shuang / Zhang, Zhenying / Hou, Suchun / Liu, Xiaoming. ·Department of Dermatology and Venereology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China. · Department of Dermatology and Venereology, The University of Hong Kong‑Shenzhen Hospital, Shenzhen, Guangdong 518053, P.R. China. ·Mol Med Rep · Pubmed #27221314.

ABSTRACT: It is currently believed that psoriasis and allergic contact dermatitis (ACD) are different diseases; however, they share clinical similarities. The involvement of T helper 17 (Th17) cells in these disorders provides a novel opportunity to investigate the relationship between them. The present study aimed to determine whether the same or overlapping inflammatory pathways are involved in the two diseases, and the influence of different types of ACD on psoriasis. Compound mouse models of Th1 or Th2‑type contact hypersensitivity (CHS) combined with imiquimod (IMQ)‑induced psoriasis‑like inflammation were established, in order to mimic the characteristics of ACD and psoriasis. Histopathology, immunohistochemistry and cytokine detection in blood serum and tissues were used to compare the differences between the mice treated with IMQ alone or IMQ combined with Th1 and Th2‑type CHS. As compared with the IMQ‑treated mice or IMQ-treated Th1‑type CHS mice, the mice with Th2‑type CHS treated with IMQ exhibited more serious psoriasis‑like inflammation with increased epidermal thickness and infiltrating cells in the derma. High mRNA expression levels of interleukin (IL)‑17, IL‑22, IL‑23, TNF‑α and RORγt were detected in back skin lesions. Additionally, high levels of IL‑17 and IL‑22 in blood serum were detected in IMQ‑treated mice combined with Th2‑type CHS. The mice treated with IMQ alone, and IMQ treatment combined with Th1‑type CHS had a comparable psoriasis‑like inflammatory response in the back skin. In conclusion, these data demonstrate that Th2‑type CHS exacerbated the IMQ‑treated psoriatic inflammation of mice via the IL‑23/IL‑17 axis. Th17 cells and associated pathways may link ACD and psoriasis. Therefore, patients with psoriasis should avoid contact with specific sensitizers, such as fragrance and rubber products, which may induce Th2 polarization.

22 Article Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease. 2016

Zhou, Fusheng / Cao, Hongzhi / Zuo, Xianbo / Zhang, Tao / Zhang, Xiaoguang / Liu, Xiaomin / Xu, Ricong / Chen, Gang / Zhang, Yuanwei / Zheng, Xiaodong / Jin, Xin / Gao, Jinping / Mei, Junpu / Sheng, Yujun / Li, Qibin / Liang, Bo / Shen, Juan / Shen, Changbing / Jiang, Hui / Zhu, Caihong / Fan, Xing / Xu, Fengping / Yue, Min / Yin, Xianyong / Ye, Chen / Zhang, Cuicui / Liu, Xiao / Yu, Liang / Wu, Jinghua / Chen, Mengyun / Zhuang, Xuehan / Tang, Lili / Shao, Haojing / Wu, Longmao / Li, Jian / Xu, Yu / Zhang, Yijie / Zhao, Suli / Wang, Yu / Li, Ge / Xu, Hanshi / Zeng, Lei / Wang, Jianan / Bai, Mingzhou / Chen, Yanling / Chen, Wei / Kang, Tian / Wu, Yanyan / Xu, Xun / Zhu, Zhengwei / Cui, Yong / Wang, Zaixing / Yang, Chunjun / Wang, Peiguang / Xiang, Leihong / Chen, Xiang / Zhang, Anping / Gao, Xinghua / Zhang, Furen / Xu, Jinhua / Zheng, Min / Zheng, Jie / Zhang, Jianzhong / Yu, Xueqing / Li, Yingrui / Yang, Sen / Yang, Huanming / Wang, Jian / Liu, Jianjun / Hammarström, Lennart / Sun, Liangdan / Wang, Jun / Zhang, Xuejun. ·Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, China. · BGI-Shenzhen, Shenzhen, China. · iCarbonX, Shenzhen, China. · Department of Biology, University of Copenhagen, Copenhagen, Denmark. · Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, China. · School of Biological Science and Medical Engineering, Southeast University, Nanjing, China. · Department of Dermatology, China-Japan Friendship Hospital, Beijing, China. · Department of Dermatology, No. 2 Hospital, Anhui Medical University, Hefei, China. · Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. · Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, China. · Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. · Department of Dermatology, Huashan Hospital and Collaborative Innovation Center of Complex and Severe Skin Disease, Fudan University, Shanghai, China. · Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. · Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. · Department of Dermatology, Peking University People's Hospital, Beijing, China. · Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · James D. Watson Institute of Genome Sciences, Hangzhou, China. · Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. · Princess Al-Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. · Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China. · Department of Medicine, University of Hong Kong, Hong Kong, China. · State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China. ·Nat Genet · Pubmed #27213287.

ABSTRACT: The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

23 Article Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population. 2016

Yin, Xianyong / Wineinger, Nathan E / Wang, Kai / Yue, Weihua / Norgren, Nina / Wang, Ling / Yao, Weiyi / Jiang, Xiaoyun / Wu, Bo / Cui, Yong / Shen, Changbing / Cheng, Hui / Zhou, Fusheng / Chen, Gang / Zuo, Xianbo / Zheng, Xiaodong / Fan, Xing / Wang, Hongyan / Wang, Lifang / Lee, Jimmy / Lam, Max / Tai, E Shyong / Zhang, Zheng / Huang, Qiong / Sun, Liangdan / Xu, Jinhua / Yang, Sen / Wilhelmsen, Kirk C / Liu, Jianjun / Schork, Nicholas J / Zhang, Xuejun. ·From the Institute of Dermatology, Department of Dermatology of The First Affiliated Hospital. Key lab of Dermatology Ministry of Education, Anhui Medical University, Hefei, China (Yin, Jiang, Wu, Cui, Shen, Cheng, Zhou, Chen, Zuo, Zhend, Fan, Wang, Sun, Yang, Zhang) · the Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, China (Yin, Zhang, Huang, Xu, Zhang) · the The Scripps Translational Science Institute, La Jolla, California, USA (Yin, Wineinger, Schork) · the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, USA (Yin, Schork) · Human Biology, J. Craig Venter Institute, La Jolla, California, USA (Yin, Schork) · the Department of Genetics, and Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, USA (Yin) · the Scripps Health, La Jolla, California, USA (Wineinger) · the Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, China (Wang) · the Peking University Sixth Hospital, Peking University Institute of Mental Health · Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Yue, Wang) · the Peking University Sixth Hospital, Peking University Institute of Mental Health · Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China (Yue, Wang) · the Human Genetics, Genome Institute of Singapore, Singapore (Norgren, Wang, Liu) · the Institute of Mental Health, Singapore (Norgren, Wang, Liu) · the Institute of Mental Health, Singapore (Lee) · the Saw Swee Hock School of Public Health, National University of Singapore, Singapore 138672, Singapore (Tai, Liu). ·J Psychiatry Neurosci · Pubmed #27091718.

ABSTRACT: BACKGROUND: Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. METHODS: We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. RESULTS: We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants ( LIMITATIONS: Our sample size was relatively small. The findings of 5 CONCLUSION: We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.

24 Article Juvenile generalized pustular psoriasis with IL36RN mutation treated with short-term infliximab. 2016

Pan, Junwei / Qiu, Li / Xiao, Ting / Chen, Hong-Duo. ·Department of Dermatology, No. 1 Hospital, China Medical University, 155 North Nanjing Street, Shenyang, 110001, China. ·Dermatol Ther · Pubmed #26627198.

ABSTRACT: A 8-year-old Chinese boy with generalized pustular psoriasis (GPP) refractory to cyclosporine and methylprednisolone was treated successfully with two infusions of infliximab 3.3 mg/kg. He remained in remission for 21 months. Direct sequencing of IL36RN gene showed a homozygous mutation, c.115 + 6T>C. Juvenile GPP is a rare severe form of psoriasis occasionally associated with life-threatening complications. Like acitretin, cyclosporine and methotrexate, infliximab has been reported to be effective for juvenile GPP in case reports. However, there is a lack of data in the optimal treatment course of infliximab for juvenile GPP. Prolonged administration of these medications may cause toxic or fatal complications. We suggest that short-term infliximab regimen should be recommended as a choice for acute juvenile GPP refractory to traditional systemic therapies. WBC count and CRP are sensitive parameters to reflect the disease activity and evaluate the effectiveness of treatment. Monitoring CD4 T lymphocyte count, preventing and correcting CD4 lymphocytopenia are important in the treatment course of juvenile GPP.

25 Article Down-regulation of the Th1, Th17, and Th22 pathways due to anti-TNF-α treatment in psoriasis. 2015

Luan, Li / Han, Shixin / Wang, Hua / Liu, Xiaoming. ·Department of Dermatology and Venereology, The Affiliated Zhongshan Hospital of DaLian University, 116001, China. · Department of Dermatology and Venereology, 1st Affiliated Hospital of DaLian Medical University, 116011, China. · Department of Dermatology and Venereology, 1st Affiliated Hospital of DaLian Medical University, 116011, China; Department of Dermatology and Venereology, Shenzhen Hospital of Hong Kong University, 518053, China. Electronic address: lxmdl_1956@126.com. ·Int Immunopharmacol · Pubmed #26585971.

ABSTRACT: BACKGROUND: Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis. OBJECTIVE: To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response. METHODS: This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α). RESULTS: At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines. CONCLUSION: The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis.

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