Objective:Erythroderma is an uncommon and severe skin disorder with many underlying causes and identifying its etiology can facilitate further treatments.This study was performed to evaluate the clinical profile and e...Objective:Erythroderma is an uncommon and severe skin disorder with many underlying causes and identifying its etiology can facilitate further treatments.This study was performed to evaluate the clinical profile and etiology of erythroderma.Methods:We collected the data on 136 patients diagnosed with erythroderma with respect to the epidemiological,clinical,biological,and histological data,treatments,and outcomes in The First Affiliated Hospital of Ningbo University from 2011 to 2021.The analyses of qualitative data were performed with the chi-square test or Fisher’s exact test.The groups of quantitative data were compared using a t-test or analysis of variance.Results:The patients’mean age in this study was 65.00±16.51 years,with a male:female ratio of 5.8:1.0.Acute onset occurred in 27 patients(19.9%)and was associated with drug reactions(P=0.002).The mean length of stay was 19.18±9.75 days.Clinical characteristics were dominated by pruritus(135,99.3%),fever(44,32.4%),edema(82,60.3%),nail changes(14,10.3%),arrhythmia(16,11.8%),and superficial lymphadenopathy(57,41.9%).Combined with biopsy,history inquiry and laboratory testing,this study found that most common causative factor was pre-existing dermatoses(107,78.7%),followed by drug reactions(15,11.0%),malignancies(8,5.9%),and undetermined etiology(6,4.4%).Among the pre-existing dermatoses,eczema was the most common etiology(33.9%).We also found that psoriasis,solar dermatitis,hypereosinophilic syndrome,atopic dermatitis,scabies,pemphigus foliaceus,and pityriasis rubra pilaris were causes of erythroderma.In the drug-induced group,anticonvulsants were the most frequently implicated drug.Compared to other cause diseases,patients with psoriasis had a significant higher rate of fever(P=0.022),nail changes(P<0.001),arthralgia(P<0.001),and infection(P=0.007).Eosinophilia and an increased immunoglobulin E concentration were associated with hypereosinophilic syndrome(P=0.005)and eczema(P=0.032),respectively compared to other cause diseases.The infection rate was s展开更多
Transient receptor potential vanilloid 1(TRPV1)channel plays an important role in a wide range of physiological and pathological processes,and a comprehensive understanding of TRPV1 gating will create opportunities fo...Transient receptor potential vanilloid 1(TRPV1)channel plays an important role in a wide range of physiological and pathological processes,and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention.Recent incredible advances in cryo-electron microscopy(cryo-EM)have yielded high-resolution structures of all TRPV subtypes(TRPV1-6)and all of them share highly conserved six transmembrane(TM)domains(S1-S6).As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist(capsaicin or resiniferatoxin),TM helices S1 to S4 form a bundle that remains quiescent during channel activation,highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels.Here,however,we argue that the structural dynamics rather than quiescence of S1-S4 domains is necessary for capsaicin-mediated activation of TRPV1.Using fluorescent unnatural amino acid(flUAA)incorporation and voltage-clamp fluorometry(VCF)analysis,we directly observed allostery of the S1-S4 bundle upon capsaicin binding.Covalent occupation of VCF-identified sites,single-channel recording,cell apoptosis analysis,and exploration of the role of PSFL828,a novel non-vanilloid agonist we identified,have collectively confirmed the essential role of this coordinated S1-S4 motility in capsaicin-mediated activation of TRPV1.This study concludes that,in contrast to cryo-EM structural studies,vanilloid agonists are also required for S1-S4 movement during TRPV1 activation.Redefining the gating process of vanilloid agonists and the discovery of new non-vanilloid agonists will allow the evaluation of new strategies aimed at the development of TRPV1 modulators.展开更多
基金the Medical Health Science and Technology Project of Zhejiang Province(No.2022PY022)We thank the patients in this study。
文摘Objective:Erythroderma is an uncommon and severe skin disorder with many underlying causes and identifying its etiology can facilitate further treatments.This study was performed to evaluate the clinical profile and etiology of erythroderma.Methods:We collected the data on 136 patients diagnosed with erythroderma with respect to the epidemiological,clinical,biological,and histological data,treatments,and outcomes in The First Affiliated Hospital of Ningbo University from 2011 to 2021.The analyses of qualitative data were performed with the chi-square test or Fisher’s exact test.The groups of quantitative data were compared using a t-test or analysis of variance.Results:The patients’mean age in this study was 65.00±16.51 years,with a male:female ratio of 5.8:1.0.Acute onset occurred in 27 patients(19.9%)and was associated with drug reactions(P=0.002).The mean length of stay was 19.18±9.75 days.Clinical characteristics were dominated by pruritus(135,99.3%),fever(44,32.4%),edema(82,60.3%),nail changes(14,10.3%),arrhythmia(16,11.8%),and superficial lymphadenopathy(57,41.9%).Combined with biopsy,history inquiry and laboratory testing,this study found that most common causative factor was pre-existing dermatoses(107,78.7%),followed by drug reactions(15,11.0%),malignancies(8,5.9%),and undetermined etiology(6,4.4%).Among the pre-existing dermatoses,eczema was the most common etiology(33.9%).We also found that psoriasis,solar dermatitis,hypereosinophilic syndrome,atopic dermatitis,scabies,pemphigus foliaceus,and pityriasis rubra pilaris were causes of erythroderma.In the drug-induced group,anticonvulsants were the most frequently implicated drug.Compared to other cause diseases,patients with psoriasis had a significant higher rate of fever(P=0.022),nail changes(P<0.001),arthralgia(P<0.001),and infection(P=0.007).Eosinophilia and an increased immunoglobulin E concentration were associated with hypereosinophilic syndrome(P=0.005)and eczema(P=0.032),respectively compared to other cause diseases.The infection rate was s
基金supported by the Natural Science Foundation of Jiangsu Province(BK20202002)the National Natural Science Foundation of China(81603409,31900808,81902480,21977021,31570832,31971146,and 31971042)+4 种基金Innovation and Entrepreneurship Talent Program of Jiangsu ProvinceState Key Laboratory of Utilization of Woody Oil Resource(2019XK2002)the Natural Science Foundation of Hunan Province(2018JJ1012)Hunan“Huxiang”High-level Talent Program(2021)“Xing Yao”Leading Scholars of China Pharmaceutical University(2021)。
文摘Transient receptor potential vanilloid 1(TRPV1)channel plays an important role in a wide range of physiological and pathological processes,and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention.Recent incredible advances in cryo-electron microscopy(cryo-EM)have yielded high-resolution structures of all TRPV subtypes(TRPV1-6)and all of them share highly conserved six transmembrane(TM)domains(S1-S6).As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist(capsaicin or resiniferatoxin),TM helices S1 to S4 form a bundle that remains quiescent during channel activation,highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels.Here,however,we argue that the structural dynamics rather than quiescence of S1-S4 domains is necessary for capsaicin-mediated activation of TRPV1.Using fluorescent unnatural amino acid(flUAA)incorporation and voltage-clamp fluorometry(VCF)analysis,we directly observed allostery of the S1-S4 bundle upon capsaicin binding.Covalent occupation of VCF-identified sites,single-channel recording,cell apoptosis analysis,and exploration of the role of PSFL828,a novel non-vanilloid agonist we identified,have collectively confirmed the essential role of this coordinated S1-S4 motility in capsaicin-mediated activation of TRPV1.This study concludes that,in contrast to cryo-EM structural studies,vanilloid agonists are also required for S1-S4 movement during TRPV1 activation.Redefining the gating process of vanilloid agonists and the discovery of new non-vanilloid agonists will allow the evaluation of new strategies aimed at the development of TRPV1 modulators.
