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Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma:results from a retrospective multicenter trial

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Frontiers of Medicine 2023年第5期17卷 878-888页

作者： Elias A.T.Koch Anne Petzold Anja Wessely Edgar Dippel Markus Eckstein Anja Gesierich Ralf Gutzmer Jessica C.Hassel Harald Knorr Nicole Kreuzberg Ulrike Leiter Carmen Loquai Friedegund Meier Markus Meissner Peter Mohr Claudia Pföhler Farnaz Rahimi Dirk Schadendorf Max Schlaak Kai-Martin Thoms Selma Ugurel Jochen Utikal Michael Weichenthal Beatrice Schuler-Thurner Carola Berking Markus V.Heppt Department of dermatology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Comprehensive Cancer center Erlangen—European Metropolitan Area of Nürnberg(CCC ER-EMN) 91054ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Bavarian Cancer Research center(BZKF) Uniklinikum ErlangenÖstliche Stadtmauerstraße 3091054ErlangenGermany Department of dermatology Ludwigshafen Medical Center67059LudwigshafenGermany Institute of Pathology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg91054ErlangenGermany Department of dermatology University Hospital Würzburg97080WürzburgGermany Skin Cancer center Minden Department of DermatologyMühlenkreiskliniken AöRRuhr UniversityBochum Campus Minden32423MindenGermany Skin Cancer center Department of Dermatology and National Center for Tumor Diseases(NCT)University Hospital Heidelberg69120HeidelbergGermany Department of Ophthalmology Uniklinikum ErlangenFriedrich-Alexander-University Erlangen-Nürnberg(FAU)91054ErlangenGermany Department of dermatology and Venereology Skin Cancer Center at the Center of Integrated Oncology(CIO)Köln BonnUniversity Hospital of Cologne50937CologneGermany Department of dermatology Center for DermatooncologyUniversity Hospital Tübingen72056TübingenGermany Department of dermatology University Medical Center Mainz55131MainzGermany Skin Cancer center at the University Cancer center Dresden and National center for Tumor Diseases&Department of dermatology University Hospital Carl Gustav Carus01307DresdenGermany Department of dermatology Venereology and AllergologyGoethe University60590Frankfurt am MainGermany Department of dermatology Elbeklinikum21614BuxtehudeGermany Department of dermatology Saarland University Medical School66421Homburg/SaarGermany Department of dermatology and Allergy Munich University Hospital(LMU)81377MunichGermany Departmen

Metastases of uveal melanoma(UM)spread predominantly to the liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this analysis.Patients were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort A.Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词： uveal melanoma liver-directed therapy immune checkpoint blockade SIRT anti-PD-1 anti-CTLA-4

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Chinese herbal medicine Yougui Pill reduces exogenous glucocorticoid-induced apoptosis in anterior pituitary cells

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Neural Regeneration Research 2016年第12期11卷 1962-1968页

作者： Yong-zhi Ji Long Geng Hong-bo Zhou Hua-chen Wei Hong-duo Chen Department of dermatology Second Hospital of Jilin University Department of dermatology First Hospital of China Medical University Department of dermatology Mount Sinai Medical Center

Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill（YGP）, a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated m RNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated m RNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.

关键词： nerve regeneration Yougui Pill glucocorticoid apoptosis Bcl-2 cytochrome c caspase-3 caspase-9 mitochondrial membrane potential neural regeneration

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Efficacy and safety of ixekizumab in Chinese patients with plaque psoriasis

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Chinese Medical Journal 2023年第3期136卷 360-361页

作者： He Huang Min Chen Wenjuan Wu Tianhui Yang Hao Liu Zhengwei Zhu Wenjun Wang Sen Yang Xian Ding Hui Wang Yujun Sheng Yaohua Zhang Min Li Xuejun Zhang Department of dermatology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230031China Ferry Institute of dermatology HefeiAnhui 230000China Boao Super Hospital Dermatology Center QionghaiHainan 571437China Department of dermatology Dushu Lake Hospital Affiliated to Soochow University(Medical Center of Soochow UniversitySuzhou Dushu Lake Hospital)SuzhouJiangsu 215125China Department of dermatology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215006China Department of dermatology Institute of DermatologyHuashan HospitalFudan UniversityShanghai 200040China

To the Editor:Psoriasis is a common,chronic papulosquamous skin disease occurring worldwide,presenting at any age,and leading to a substantial burden for individuals and society.Interleukin(IL)-17A is considered the key effector cytokine inducing psoriatic inflammation and tissue damage.[1]Ixekizumab is a humanized monoclonal immunoglobulin G specifically binding to and inhibiting IL-17A.The efficacy and safety of ixekizumab in patients with psoriasis have been clearly demonstrated in several randomized clinical trials,namely UNCOVER-1,UNCOVER-2,UNCOVER-3,and UNCOVER-J.[2,3]However,the clinical research data on ixekizumab in Chinese psoriasis patients remain limited.

关键词： patients psoriasis clinical

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Cellular signaling in sinecatechins-treated external genital and perianal warts: unraveling the mechanism of action of a botanical therapy

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Virologica Sinica 2015年第3期30卷 214-217页

作者： Harrison P Nguyen Hung Q Doan Peter Rady Stephen K Tyring Department of dermatology Baylor College of Medicine Department of dermatology University of Texas Houston Health Science Center center for Clinical Studies

Dear Editor,Derived from green tea leaves,sinecatechins(Veregen)ointment,15%is a topical therapy that is FDA-approved to treat human papillomavirus(HPV)-induced external genital and perianal warts(EGW)in immunocompetent patients aged 18 years and older.In two phase 3 trials enrolling over 1,000 participants with EGW,a 16-week treatment regimen with sinecatechins ointment resulted in higher rates of complete clearance of all

关键词： genital papillomavirus clearance older regimen approved signaling transcriptase salient biopsy

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Herbal Medicines Prevent the Development of Atopic Dermatitis by Multiple Mechanisms

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Chinese Journal of Integrative Medicine 2019年第2期25卷 151-160页

作者： MAN Mao-qiang HU Li-zhi Peter M.Elias dermatology Service Veterans Affairs Medical Center Department of dermatology University of California San Francisco School of Basic Medical Sciences Tianjin Medical University

Atopic dermatitis(AD) is among the most common skin disorders in humans. Although a variety of regimens are available for the treatment of AD, preventive approaches are limited. Recent studies have demonstrated that certain naturally-occurring herbal medicines are effective in preventing the development of AD via divergent mechanisms, such as inhibiting cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or enhancement of epidermal permeability barrier function. Yet, they exhibit few adverse effects. Since herbal medicines are widely available, inexpensive and generally safe, they could represent an ideal approach for preventing the development of AD, in both highly developed and developing countries.

关键词： herbal medicines T cells cytokines permeability barrier dermatitis

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Glutathione S-transferase P1 IlelO5Val Polymorphism and Male Infertility Risk： An Updated Meta-analysis

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Chinese Medical Journal 2017年第8期130卷 979-985页

作者： Xue-Kun Huang Yong-Han Huang Juan-Hua Huang Jing-Yao Liang Department of Obstetrics and Gynaecology Reproductive Medicine Center The First People's Hospital of Foshan Foshan Guangdong 528000 China Department of dermatology Institute of Dermatology Guangzhou Medical University Guangzhou Guangdong 510095 China Department of dermatology Institute of Dermatology Guangzhou Institute of Dermatology Guangzhou Guangdong 510095 China

Background： Several studies concerning the association between glutathione S-transferase P1 （GSTP1） Ilel05Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a recta-analysis. Methods： The PubMed, EMBASE, China National Knowledge Infrastructure （CNKI）, and Wanfang databases were searched. Odds ratios （ORs） with 95% confidence intervals （C/s） were calculated to estimate the strength of the association. Results： A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 llel05Val polymorphism and male infertility in the overall population, but significant associations were lbund under the dominant （OR = 1.23, 95% CI = 1.04-1.46, F = 32.2%） and heterozygote （OR = 1.29, 95% C1 - 1.08-1.53, F = 26.8%） models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium （HWE）. Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model （OR = 1.25, 95% CI = 1.03-1.52, F = 44.1%）. Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found. Conclusions： The GS-FP1 lle105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.

关键词： Glutathione S-transferase PI Male Infertility： Polymorphism

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Non-invasive detection technology in port-wine stain treatment

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Chinese Medical Journal 2022年第21期135卷 2535-2537页

作者： Xue Wang Yangxue Fu Yan Liu Wenjia Nie Xingyu Su Xianbiao Zou Rusong Meng Yan Li Juan Tao Department of dermatology The First Affiliated HospitalMedical College of Shihezi UniversityShiheziXinjiang 832008China Department of dermatology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology(HUST)WuhanHubei 430022China Hubei Engineering Research center for Skin Repair and Theranostics WuhanHubei 430022China Department of dermatology of the Fourth Medical center of People’s Liberation Army General Hospital Beijing 100048China Department of dermatology Specialty Medical Center of the Air ForcePeople’s Liberation ArmyBeijing 100142China

Port-wine stain(PWS)is a type of disfiguring disease and its molecular pathogenesis remains ambiguous.The current gold standard treatment for PWS is pulsed dye laser(PDL);[1]meanwhile hematoporphyrin monomethyl ether-photodynamic therapy(HMME-PDT)has also been utilized for clinical use for 5 years.[2]Due to the vascular heterogeneity,it is difficult to predict and evaluate its efficacy with naked eyes.Therefore,a technology that is consistent,repeatable,and non-invasive will be required to provide accurate images and quantitative evaluation indicators.In this study,we have reviewed dermoscopy,reflectance confocal microscopy(RCM),high-frequency ultrasound(HFUS),optical coherence tomography(OCT),and laser speckle imaging(LSI),etc.in predicting efficacy,intra-operative monitoring,and objective evaluation of effectiveness of PWS treatment[Figure 1].

关键词： treatment laser Figure

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Clinical and genetic findings in 13 Chinese children with keratinopathic ichthyosis

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Pediatric Investigation 2023年第3期7卷 168-176页

作者： Zhou Yang Zhe Xu Rui He Xin Xiang Bin Zhang Lin Ma Department of dermatology Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Department of dermatology Shunyi Maternal and Children’s Hospital of Beijing Children’s HospitalBeijingChina

Importance:Keratinopathic ichthyosis(KPI)represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the KRT1,KRT2,or KRT10 genes.In KPI,the relationship between genotype and phenotype is complex.Objective:To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.Methods:Clinical data were collected from 13 children diagnosed with KPI,and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel,and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.Results:Genetic analysis identified missense mutations in either KRT1 or KRT10 in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis.A missense hotspot mutation in KRT2 was identified in one patient with superficial epidermolytic ichthyosis.Additionally,two truncation mutations in KRT10 were detected,leading to the development of generalized ichthyosiform erythroderma.Ear malformation and ectropion at birth,scalp involvement,and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.Interpretation:We analyzed the genotype-phenotype correlations in KPI,revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics.Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.

关键词： Epidermolytic ichthyosis Ichthyosis with confetti Keratinopathic ichthyosis KRT1 KRT10 KRT2

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Targeting autophagy and beyond:Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4688-4714页

作者： Jing Ye Jin Zhang Yanghui Zhu Lian Wang Xian Jiang Bo Liu Gu He Department of dermatology State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China PLaboratory of dermatology Clinical Institute of Inflammation and Immunology(CIl)Frontiers Science Center for Disease Related Molecular NetworkChengdu 610041China

AbstracBteclin-1 is the firstly-identified mammalian protein of the autophagy machinery,which functions as a molecular scaffold for the assembly of PI3KC3(class II phosphatidylinositol 3 kinase)complex,thus controlling autophagy induction and other cellular trafficking events.Notably,there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes,including tumor suppression and progression as well as resistance to cancer therapeutics and CSC(cancer stem-like cell)maintenance.More importantly,Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers.In this review,we provide a comprehensive survey of the structure,functions,and regulations of Beclin-1,and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology.Moreover,we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy,providing novel insights into a promising strategy for regulating Beclin-1 to improvecancer therapeutics in thefuture.

关键词： Beclin-1 PI3KC3 complex Autophagy Non-autophagy Cancer therapy

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The update of treatment strategies in pediatrics with generalized pustular psoriasis in China

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Pediatric Investigation 2023年第3期7卷 191-198页

作者： Yunliu Chen Xin Xiang Zhaoyang Wang Chaoyang Miao Zigang Xu Department of dermatology Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina

Generalized pustular psoriasis(GPP)is a severe subtype of psoriasis,commonly combined with systemic inflammation.Gene mutations have been found to be associated with GPP and vary by ethnicity.Systemic treatments are usually required for the severity and potential complications of GPP.However,there is no common consensus in China,especially among pediatric patients,whose data are scarce.Acitretin,methotrexate,and cyclosporine are widely used in pediatrics with GPP,while the adverse effects should be highlighted.The emergence of different biological agents brings us into a new era.This article discusses the genetic background of Chinese patients and demonstrates the evidence of treatment in pediatrics with GPP.

关键词： Generalized pustular psoriasis Pediatrics Treatment

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