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BackgroundAcrodermatitis continua of Hallopeau (ACH) is a rare, sterile pustular psoriasis variant refractory to many conventional treatments. The eruption typically occurs after local trauma or infection; other etiologies include neural, inflammatory, and genetic causes. Herein we reported a single case of a 64-year-old patient with ACH that was successfully treated with spesolimab for 19 weeks.Case summaryA 64-year-old Chinese male with no personal or known family history of psoriasis had recurrent episodes of redness, swelling, and pustules in the nail bed on seven fingers with progressive degeneration of the nails. The patient was monitored as to the evolution of the disease over half of a year before he referred his case to our attention. A diagnosis of ACH was made, allowing for the administration of local steroids and oral acitretin. However, after 3 months of acitretin treatment, no improvement was observed. In December 2023, this patient came to our inpatient department; his modified nail psoriasis severity index score was 32. Before starting treatment, a comprehensive set of laboratory and instrumental tests were all found to be negative. Moreover, whole-exome sequencing was performed in our patient, and it revealed no rare coding variant in IL36RN, CARD14, or AP1S3. Therefore, the patient was administrated with a dose of 900 mg spesolimab. After 10 days, the patient showed a significant decrease in discomfort and pain. In order to strengthen the therapeutic effect, he was given the second dose of 900 mg spesolimab after 4 weeks. After 19 weeks of spesolimab treatment, the patient’s nail lesions showed complete resolution, and no adverse effects were reported.ConclusionThe case report suggests that spesolimab may offer significant therapeutic benefits for ACH.

Background: Psoriatic arthritis (PsA) is an immune-mediated form of chronic inflammatory arthritis associated with psoriasis (PsO). It constitutes a significant comorbidity of PsO and is distinguished by the presence of widespread musculoskeletal inflammation. Objective: The aim of this study is to precisely detect asymptomatic PsA using ultrasound (US) examinations and to distinguish between various stages of PsO. Methods: All patients with moderate-to-severe PsO, who consented to undergo musculoskeletal US examinations during their hospitalization between September 2020 and January 2022, were enrolled in the study. We compared patients' demographic characteristics, comorbidities, disease duration, relevant laboratory parameters, and musculoskeletal US findings. Results: A total of 547 patients with PsO were included in the study, and 114 of them received a diagnosis of PsA. Furthermore, 16.45 % of patients with moderate to severe PsO displayed subclinical PsA. We observed a significantly higher frequency of abnormal US findings in patients with PsA compared to those without PsA, with a sensitivity of 95.61 % and a specificity of 79.22 %. Additionally, the incidence of enthesitis and synovitis varied significantly between PsA and non-PsA patients, and they were identified as independent variables predicting the presence of PsA. Furthermore, the interphalangeal joint, knee joint, and calcaneal tendon were the most frequently affected areas in PsA, as indicated by the observed US changes. Conclusion: Ultrasound examination proves to be a valuable tool for detecting subclinical PsA, facilitating early screening of the condition. Particular attention should be directed towards changes in the interphalangeal joint, knee joint, and calcaneal tendon when reviewing ultrasound images of asymptomatic patients.

BackgroundAcquired reactive perforating collagenosis (ARPC) poses a clinical challenge with an unclear pathogenesis. This disease has been frequently proven resistant to immunosuppressive treatments, significantly affecting the quality of life of patients. In this report, we highlight the efficacy of baricitinib as a viable option for maintenance therapy in ARPC.Case summaryAn 81-year-old woman presented to our hospital with recurrent pruritus and cup-like ulcerated lesions on her trunk and limbs persisting for 1 year. She exhibited limited response to oral antihistamines and topical steroids. Past medical history revealed a prolonged history of coronary heart disease and type 2 diabetes spanning several years to decades. Histopathological examination revealed cup-shaped depressions filled with necrotic inflammatory debris. In the dermis, a mixed inflammatory infiltrate composed of lymphocytes and histiocytes was observed. Van Gieson staining indicated the elimination of fibrous tissue extending from the dermis into the epidermis. Consequently, a diagnosis of ARPC was established. Due to the inadequate response to conventional treatments and the severe itching, we initiated baricitinib therapy for ARPC, resulting in gradual symptom improvement. Follow-up assessments showed no adverse reactions and normal laboratory findings.ConclusionThe case report suggests that baricitinib might offer significant therapeutic benefits for ARPC.

Abstract. Background:. Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. Methods:. This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. Results:. At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%-69%) and 45% (low vs. placebo, 95% CI 26%-64%), with both P values

Abstract Background Psoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles. Methods Plasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models. Results Males suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline. Conclusions Sex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.

Abstract Secukinumab is effective in treating patients with moderate‐to‐severe plaque psoriasis. However, most studies assessing its effectiveness in routine clinical settings in China are mostly single‐center studies with a limited sample size. The objective of this study was to assess secukinumab's efficacy, treatment patterns, and characteristics in patients with moderate‐to‐severe plaque psoriasis. This 24‐week, multicenter (n = 5) retrospective study analyzed the data of Chinese adult patients with moderate‐to‐severe plaque psoriasis who initiated secukinumab treatment between May 2019 and March 2020. The Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator's Global Assessment Modified 2011 (IGA mod 2011), and Dermatology Life Quality Index (DLQI) were assessed. Dermatologists documented the treatment dosage and modification reasons. Of the 244 secukinumab‐naïve patients, most were men (73.4%, 179/244) and weighed 60–90 kg (72.8%, 177/243). The mean (SD) age at secukinumab initiation was 38.1 (11.6) years, and the disease duration was 13.5 (7.9) years. Most patients (97.1%, 237/244) received secukinumab 300 mg. At weeks 4, 12, 16, and 24, the proportion of patients achieving PASI 75 (≥75% reduction from baseline) was 40.0%, 92.1%, 88.4%, and 88.9%, respectively; PASI 90 was 15.0%, 73.7%, 81.4%, and 68.3%, respectively; and PASI 100 was 8.7%, 40.8%, 58.1%, and 41.3%, respectively. During the same periods, BSA and IGA mod 2011 showed similar improvement trends. An increasing proportion of patients achieved DLQI of 0–1 (21.6%, 65.7%, 75.0%, and 80.3%, respectively). Treatment modification was highest at week 12. The average interval between two administrations after week 4 was 62.95 days. Secukinumab was highly effective in improving the PASI, IGA, BSA, and DLQI in Chinese patients with moderate‐to‐severe plaque psoriasis throughout the first 24 weeks. The treatment pattern for Chinese patients differs from that in the clinical guidelines.

Abstract Introduction Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening skin disease. The global Effisayil 1 study investigated the efficacy and safety of spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, in patients experiencing GPP flare. This analysis aimed to explore the efficacy and safety of spesolimab in the Chinese subgroup of Effisayil 1. Methods Effisayil 1 was a multicenter, randomized, double-blind, placebo-controlled phase II study. Eligible patients with a GPP flare were randomly assigned (2:1) to receive a single intravenous dose of spesolimab (900 mg) or placebo on day 1. On day 8, patients who had persistent symptoms that met a predefined criterion could receive open-label spesolimab. After day 8, patients with recurrent flares following clinical response could receive rescue treatment with open-label spesolimab. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation sub-score of 0 at week 1. The key secondary end point was a GPPGA total score of 0 or 1 at week 1. Results Eleven Chinese patients were randomized, with five patients receiving spesolimab and six receiving placebo. At week 1, 60.0% (3/5) of patients in the spesolimab group and 16.7% (1/6) of patients in the placebo group achieved a GPPGA pustulation sub-score of 0 (risk difference 43.3%; 95% CI –22.6, 86.2); 60.0% and 16.7% of patients in the spesolimab and placebo group, respectively, achieved a GPPGA total score 0 or 1 (risk difference 43.3%; 95% CI –22.6, 86.2). Overall, four patients in each group of the spesolimab and the placebo groups reported at least one adverse event (AE) by week 1, with two and three reporting drug-related AEs, respectively. One patient reported a serious AE that was not considered to be drug related. No death occurred during the study period. Conclusion In the Chinese subgroup of the Effisayil 1 study, more patients receiving spesolimab experienced lesion clearance than those on placebo at week 1, with an acceptable safety profile that was consistent with the global study population. Trial Registration NCT03782792.

BackgroundThe systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are both novel biomarkers and predictors of inflammation. Psoriasis is a skin disease characterized by chronic inflammation. This study aimed to investigate the potential association between SII, SIRI, and adult psoriasis.MethodsData of adults aged 20 to 80 years from the National Health and Nutrition Examination Survey (NHANES) (2003–2006, 2009–2014) were utilized. The K-means method was used to group SII and SIRI into low, medium, and high-level clusters. Additionally, SII or SIRI levels were categorized into three groups: low (1st-3rd quintiles), medium (4th quintile), and high (5th quintile). The association between SII-SIRI pattern, SII or SIRI individually, and psoriasis was assessed using multivariate logistic regression models. The results were presented as odds ratios (ORs) and confidence intervals (CIs). Restricted cubic spline (RCS) regression, subgroup, and interaction analyses were also conducted to explore the potential non-linear and independent relationships between natural log-transformed SII (lnSII) levels or SIRI levels and psoriasis, respectively.ResultsOf the 18208 adults included in the study, 511 (2.81%) were diagnosed with psoriasis. Compared to the low-level group of the SII-SIRI pattern, participants in the medium-level group had a significantly higher risk for psoriasis (OR = 1.40, 95% CI: 1.09, 1.81, p-trend = 0.0031). In the analysis of SII or SIRI individually, both SII and SIRI were found to be positively associated with the risk of psoriasis (high vs. low group OR = 1.52, 95% CI: 1.18, 1.95, p-trend = 0.0014; OR = 1.48, 95% CI: 1.12, 1.95, p-trend = 0.007, respectively). Non-linear relationships were observed between lnSII/SIRI and psoriasis (both p-values for overall < 0.05, p-values for nonlinearity < 0.05). The association between SII levels and psoriasis was stronger in females, obese individuals, people with type 2 diabetes, and those without hypercholesterolemia.ConclusionWe observed positive associations between SII-SIRI pattern, SII, SIRI, and psoriasis among U.S. adults. Further well-designed studies are needed to gain a better understanding of these findings.

Abstract. Background:. Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. Methods:. Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. Results:. A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%–11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%–12.5%) for males and 9.6% (95% CI, 7.7%–11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%–59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%–6.2%). Conclusion:. The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Abstract Introduction To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). Methods Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. Results Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. Conclusions Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

Abstract Pustular psoriasis (PP) is a chronic inflammatory disease associated with multiple complications, often with hyperthermia and hypoproteinemia, and its continued progression can be life-threatening. Toll-like receptor 7 (TLR7) induces dendritic cell (DC) production of inflammatory factors that exacerbate the inflammatory response in PP. A membrane-bound chemokine expressed on DCs, CXC motif chemokine ligand 16 (CXCL16) is overexpressed in PP lesions, and neutrophils express its receptor CXC chemokine receptor 6 (CXCR6). There are few studies on the PP immune microenvironment and it is unclear whether TLR7 and CXCL16 can be used as targets in PP therapy. Skin tissue (n = 5) and blood (n = 20) samples were collected from PP and healthy normal controls. The skin tissue transcriptome was analyzed to obtain the differentially expressed genes, and the immune microenvironment was deciphered using pathway enrichment. Tissue sequencing analysis indicated that TLR7, CXCL16, DCs, and neutrophils were involved in the PP process. The enzyme-linked immunosorbent assay, reverse transcription–PCR, and scoring table results demonstrated that TLR7 induced DC secretion of CXCL16, which enabled neutrophil activation of the secretion of the inflammatory factors interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The co-culture of neutrophils with DCs treated with TLR7 inhibitor or TLR7 agonist demonstrated that TLR7 regulated neutrophil activation, migration, and apoptosis. We constructed imiquimod-induced psoriasis-like skin lesions in wild-type, Cd11c-Cre Myd88 f/f , and Mrp8-Cre Cxcr6 f/f mice. The mouse models suggested that TLR7 might influence DC release of CXCL16 and neutrophil proinflammatory effects by interfering with the myeloid differentiation primary response gene 88 (MyD88) signaling pathway. In conclusion, the TLR7–MyD88–DC–CXCL16 axis is an important mechanism that promotes neutrophil migration to PP skin lesions and stimulates the inflammatory response.

Background: Although clinical trials and real-world data suggest that the risk of COVID-19 and its complications is not exacerbated in patients with psoriasis treated by biological agents, the evidence for this is still limited. Objectives: We aimed to assess the outcomes of COVID-19 among Chinese patients with psoriasis treated by IL-23 inhibitor, and to compare these variables in patients receiving other therapies. Methods: A cross-sectional cohort study was conducted to compare psoriasis treatment with IL-23 inhibitor to other treatment methods. All the patients received a questionnaire that contained questions about their psoriasis treatment, COVID-19 symptoms, and related risk factors. The prevalence of COVID-19 was calculated, and logistic regression analyses were performed to determine the association between treatment method and COVID-19 risk. The symptoms of COVID-19 and long COVID were described for each treatment group. Results: Between December 2022 and February 2023, 732 patients with psoriasis were included in the final analysis. 549 patients had a SARS-CoV-2 infection during the study period. Our results showed that individuals who worked outdoors had a decreased risk of COVID-19, as did those who had other allergic disease. With regard to the effect of the treatment regimens, IL-23 inhibitor treatment was associated with a decreased risk of COVID-19 compared to almost all the other treatments except acitretin. Fever was the most common symptom, but the maximum temperature and duration of fever were comparable among the treatment groups. Patients treated with IL-23 inhibitor were more likely to be asymptomatic after recovery compared to patients treated with methotrexate, narrow-bound ultra violet B, or TNF-α inhibitor. Conclusions: IL-23 inhibitor treatment may lower the risk of COVID-19 and long COVID. Thus, IL-23 inhibitor treatment might be beneficial and positively considered for patients with psoriasis who require systemic treatment during periods when there is a surge in COVID-19 cases.

BackgroundRandomized controlled trials indicated guselkumab, the first anti-interleukin-23 monoclonal antibody, is efficacious in plaque psoriasis. However, guselkumab's performance in real life is scarcely examined, especially in China.ObjectivesThis work aimed to assess the long-term effectiveness of guselkumab in actual clinical practice in China.MethodsA retrospective study was performed for plaque psoriasis cases administered guselkumab in Shanghai Skin Disease Hospital between January 2020 and September 2022.ResultsA total of 37 patients were included (29 men, 78.4%), with a mean follow-up period of 72.3 ± 26.7 weeks (range of 12–108 weeks). At baseline, clinical examination revealed a mean PASI of 12.3 ± 7.1, a mean BSA of 17.1 ± 18.1, and a mean DLQI of 7.7 ± 4.3. Twenty-two (62.9%) and 17 (48.6%) cases achieved PASI 90 and PASI 100 responses at week 28. From weeks 60 to 92, >80% of cases achieved PASI 90 and PASI 100 responses. Regarding safety, no cases of serious AEs were recorded. A total of nine cases (24.3%) had different abnormal results in HBV markers, and two were T-SPOT positive. There was no hepatitis B virus or tuberculosis outbreak in these patients.ConclusionThis real-life study confirmed the long-term efficacy and safety of guselkumab in daily clinical practice.

Abstract N6-methyladenosine (m6A) is a prevalent internal modification in eukaryotic RNAs regulated by the so-called “writers”, “erasers”, and “readers”. m6A has been demonstrated to exert critical molecular functions in modulating RNA maturation, localization, translation and metabolism, thus playing an essential role in cellular, developmental, and disease processes. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures generated by back-splicing. CircRNAs also participate in physiological and pathological processes through unique mechanisms. Despite their discovery several years ago, m6A and circRNAs has drawn increased research interest due to advances in molecular biology techniques these years. Recently, several scholars have investigated the crosstalk between m6A and circRNAs. In this review, we provide an overview of the current knowledge of m6A and circRNAs, as well as summarize the crosstalk between these molecules based on existing research. In addition, we present some suggestions for future research perspectives.

Introduction Psoriasis is an immune-related chronic skin disease, and interleukin-22 (IL-22) is involved in psoriasis pathogenesis through promoting proliferation and migration abilities of keratinocytes. Here, we analysed the role of circular RNA (circRNA) RAB3B, member RAS oncogene family (circRAB3B) in regulating the phenotypes of IL-22-induced HaCaT cells. Methods RT-qPCR was implemented to assess RNA abundance. Western blot assay was adopted to assess protein abundance. Cell proliferation capacity was examined by cell counting kit-8 (CCK8) assay and 5-ethynyl-2′-deoxyuridine (Edu) assay. Cell motility was assessed by transwell assays and wound healing assay. Flow cytometric analysis was utilized to evaluate cell cycle progression and apoptosis. The intermolecular binding relations were tested via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. CircRAB3B expression was reduced in psoriatic cutaneous specimens and IL-22-treated HaCaT cells. Results CircRAB3B overexpression hampered the proliferation, motility, and cell cycle progression and elevated the apoptotic rate of IL-22-treated HaCaT cells, and circRAB3B silencing exhibited opposite effects in IL-22-induced HaCaT cells. CircRAB3B acted as microRNA-1228-3p (miR-1228-3p) sponge in HaCaT cells, and miR-1228-3p overexpression largely overturned circRAB3B overexpression-induced effects in HaCaT cells. MiR-1228-3p interacted with phosphatase and tensin homolog (PTEN), and circRAB3B sponged miR-1228-3p to induce PTEN level. MiR-1228-3p accumulation-mediated effects were partly alleviated by PTEN overexpression in HaCaT cells upon IL-22 treatment. Conclusions CircRAB3B suppressed psoriasis progression partly through down-regulating miR-1228-3p and up-regulating PTEN.

Psoriasis is a chronic, inflammatory skin disease, frequently associated with dyslipidemia. Lipid disturbance in psoriasis affects both circulatory system and cutaneous tissue. Epidermal Langerhans cells (LCs) are tissue-resident DCs that maintain skin immune surveillance and mediate various cutaneous disorders, including psoriasis. However, the role of LCs in psoriasis development and their lipid metabolic alternation remains unclear. Here, we demonstrate that epidermal LCs of psoriasis patients enlarge with longer dendrites and possess elevated IL-23p19 mRNA and a higher level of neutral lipids when compared with normal LCs of healthy individuals. Accordantly, epidermal LCs from imiquimod-induced psoriasis-like dermatitis in mice display overmaturation, enhanced phagocytosis, and excessive secretion of IL-23. Remarkably, these altered immune properties in lesional LCs are tightly correlated with elevated neutral lipid levels. Moreover, the increased lipid content of psoriatic LCs might result from impaired autophagy of lipids. Bulk RNA-Seq analysis identifies dysregulated genes involved in lipid metabolism, autophagy, and immunofunctions in murine LCs. Overall, our data suggest that dysregulated lipid metabolism influences LC immunofunction, which contributes to the development of psoriasis, and therapeutic manipulation of this metabolic process might provide an effective measurement for psoriasis.

Psoriasis is a worldwide chronic inflammatory skin disease. The treatment of disease is usually designed according to its severity. In this research, RNA-seq was performed on 37 patients with psoriasis treated with guselkumab before and after treatment, and the patients were divided into fast responder and slow responder according to PASI score to analyze the differentially expressed genes (DEGs) between them. Moreover, The biological mechanism of psoriasis was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, and Gene Set Enrichment Analysis (GSEA) analysis. And then, this protein-protein interaction network was constructed and 17 DEGs including IL-1β, CXCL8, S100A12 and MMP9 were analyzed by GSVA. DEGs were detected by GO and KEGG analysis of target genes, which were primarily associated with immune response, neutrophil activation, neutrophil degranulation. GSEA reminded that fast responders were mainly involved in low-density neutrophils and abundant NK cells. And the GSVA showed that the DEGs were down-regulated after the early stage of the fast responder and the reverse in the slow responder by GSVA analysis. On the whole, these results indicated that these DEGs may serve as a psoriasis potential diagnostic and predictive biomarkers after been treated by guselkumab.

Abstract Background Identification and characterization of new traits with sound physiological foundation is essential for crop breeding and production management. Deep learning has been widely used in image data analysis to explore spatial and temporal information on crop growth and development, thus strengthening the power of identification of physiological traits. Taking the advantage of deep learning, this study aims to develop a novel trait of canopy structure that integrate source and sink in japonica rice. Results We applied a deep learning approach to accurately segment leaf and panicle, and subsequently developed the procedure of GvCrop to calculate the leaf to panicle ratio (LPR) of rice canopy during grain filling stage. Images of training dataset were captured in the field experiments, with large variations in camera shooting angle, the elevation and the azimuth angles of the sun, rice genotype, and plant phenological stages. Accurately labeled by manually annotating the panicle and leaf regions, the resulting dataset were used to train FPN-Mask (Feature Pyramid Network Mask) models, consisting of a backbone network and a task-specific sub-network. The model with the highest accuracy was then selected to check the variations in LPR among 192 rice germplasms and among agronomical practices. Despite the challenging field conditions, FPN-Mask models achieved a high detection accuracy, with Pixel Accuracy being 0.99 for panicles and 0.98 for leaves. The calculated LPR displayed large spatial and temporal variations as well as genotypic differences. In addition, it was responsive to agronomical practices such as nitrogen fertilization and spraying of plant growth regulators. Conclusion Deep learning technique can achieve high accuracy in simultaneous detection of panicle and leaf data from complex rice field images. The proposed FPN-Mask model is applicable to detect and quantify crop performance under field conditions. The newly identified trait of LPR should provide a high throughput protocol for breeders to select superior rice cultivars as well as for agronomists to precisely manage field crops that have a good balance of source and sink.

Abstract Background Plaque psoriasis is a refractory inflammatory skin disease. The common therapies used to treat plaque psoriasis in traditional Chinese medicine (TCM) and western medicine (WM) have distinct characteristics and advantages. Although a combination of TCM and WM therapies, adjusted to the clinical situation, is widely used, there are no systematic studies on the hierarchical selection of this treatment combination based on the severity of skin lesions. We therefore designed a randomized clinical trial to focus on the sequence of internal and external treatments of TCM in patients with mild-to-moderate plaque psoriasis and to optimize the integration of Chinese and western medicine for the treatment of patients with severe plaque psoriasis, thereby achieving high-level clinical evidence and establish treatment norms for the integrated use of Chinese and western medicines. Methods In this proposed multicenter, single-blinded, randomized controlled trial, 108 patients with mild-to-moderate plaque psoriasis will be randomly assigned to two groups in a 1:1 ratio to receive either internal or external TCM treatment, and 270 patients with severe plaque psoriasis will be randomly assigned to three groups in a 1:1:1 ratio to receive treatment with TCM or WM, or TCM + WM. All enrolled patients will receive 8 weeks of treatment. Follow-up assessments will be done 8 weeks after the treatment. The primary outcome of this study is the evaluation of efficacy and relapse rate, based on the Psoriasis Area and Severity Index, and the secondary outcome measures include determination of the affected body surface area, physician’s global assessment, pruritus scores (determined using a visual analog scale), TCM symptom score, Dermatology Life Quality Index, patient-reported quality of life score and incidence of serious adverse events. Discussion This study will provide high-level clinical evidence for internal and external TCM treatment optimization and will contribute to establishing norms for the integration of Chinese and western Medicines. Trial registration ClinicalTrials.gov, NCT03941431 . Registered on 8 May 2019.

Objective. To investigate the clinical efficacy and safety of acitretin and MTX with TLR7/MyD88/CXCL16 in the treatment of pustular psoriasis. Method. A total of 54 patients with pustular psoriasis were randomly divided into control group (n=14) and study group (n=40). MTX was used in the control group, and different doses of acitretin were used in the study group, which were divided into low-dose group (n=13), medium-dose group (n=13), and high-dose group (n=14). Symptom relief time, recurrence rate, GPPASI improvement rate, treatment response rate, BSA, DLQI score, and TLR7 and CXCL16 levels were compared among four groups. Result. The erythema, fever, and pustules disappeared in the low-dose group, the medium-dose group, and the high-dose group for a shorter time than control group, and it is shortest for the high-dose group. The low-dose, medium-dose, and high-dose groups had relatively lower recurrence rates at 1 month and 3 months (P

Generalized pustular psoriasis (GPP), the most grievous variant of psoriasis, is featured by dysregulated systemic inflammatory response. The cellular and molecular basis of GPP is poorly understood. Blood monocytes are key players of host defense and producers of inflammatory cytokines including IL-1β. How the immune response of monocytes is affected by metabolic internal environment in GPP remains unclear. Here, we performed a metabolomic and functional investigation of GPP serum and monocytes. We demonstrated a significant increase in IL-1β production from GPP monocytes. In GPP circulation, serum amyloid A (SAA), an acute-phase reactant, was dramatically increased, which induced the release of IL-1β from monocytes in a NLRP3-dependent manner. Using metabolomic analysis, we showed that GPP serum exhibited an amino acid starvation signature, with glycine, histidine, asparagine, methionine, threonine, lysine, valine, isoleucine, tryptophan, tyrosine, alanine, proline, taurine and cystathionine being markedly downregulated. In functional assay, under amino acid starvation condition, SAA-stimulated mature IL-1β secretion was suppressed. Mechanistically, at post-transcriptional level, amino acid starvation inhibited the SAA-mediated reactive oxygen species (ROS) formation and NLRP3 inflammasome activation. Moreover, the immune-modulatory effect of amino acid starvation was blocked by silencing general control nonderepressible 2 kinase (GCN2), suggesting the involvement of amino acid response (AAR) pathway. Collectively, our results suggested that decreased serum amino acids in GPP blunted the innate immune response in blood monocytes through AAR pathway, serving as a feedback mechanism preventing excessive inflammation in GPP.

Psoriasis is an immune-mediated chronic inflammatory skin disease primarily mediated by the activation of interleukin (IL)-17-producing T cells. Traditional Chinese Medicine (TCM) represents one of the most effective complementary and alternative medicine (CAM) agents for psoriasis, which provides treasured sources for the development of anti-psoriasis medications. Xiao-Yin-Fang (XYF) is an empirically developed TCM formula that has been used to treat psoriasis patients in Shanghai Changhai Hospital for over three decades. Imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was utilized to investigate the therapeutic effects of XYF by the assessment of disease severity and skin thickness. Flow cytometric assay was performed to explore the influence of XYF on skin-related immunocytes, primarily T cells. And, RNA sequencing analysis was employed to determine the alternation in gene expression upon XYF therapy. We discovered that XYF alleviated psoriasis-like skin inflammation mainly through suppressing dermal and draining lymph-node IL-17-producing γδT (γδT17) cell polarization. Moreover, XYF therapy ameliorated the relapse of psoriasis-like dermatitis and prohibited dermal γδT cell reactivation. Transcriptional analysis suggested that XYF might regulate various inflammatory signaling pathways and metabolic processes. In conclusion, our results clarified the therapeutic efficacy and inner mechanism of XYF therapy in psoriasis, which might promote its clinical application in psoriasis patients and facilitate the development of novel anti-psoriasis drugs based on the bioactive components of XYF.

Background: Although there have been many epidemiological studies, research focusing on psoriasis' health burden on a global scale is still lacking. Trends and variations in the global health burden of psoriasis are evaluated by time, age, gender, geographical location, and socioeconomic status, using disability-adjusted life years (DALYs) from the Global Burden of Disease Study.Methods: The health burden of psoriasis was evaluated by DALYs, which combined years lost to disability (a morbidity component) with years of life lost (a mortality component). The global and national DALYs number, crude DALYs rate, and age-standardized DALYs rate were obtained from the GBD 2017 study database. The corresponding human development index (HDI) was collected from the United Nations Development Programme.Results: From 1990 to 2017, the DALYs number and crude DALYs rate due to psoriasis increased by 73 and 22%, respectively. In comparison, the age-standardized DALYs rate showed a slight increase. Patients in the age range of 65–69 years bear a more significant psoriasis burden. Both males and females showed an increasing trend in burden caused by psoriasis over the past 27 years, with females bearing a more significant psoriasis burden than males. The health burden of psoriasis was substantially unequal in geography with a Gini coefficient of 0.27. The concentration indexes indicated a socioeconomic associated inequality in psoriasis burden with values of 0.22, accounting for 48.64% variance across countries (R2 = 0.4864, p < 0.001). Between-nation inequality in the distribution of psoriasis burden continued to decline throughout the past 27 years. Gini coefficients of psoriasis burden decreased from 0.280 in 1990 to 0.265 in 2017. The concentration indexes indicated the same trend with 0.236 in the 1990s and 0.223 in 2017.Conclusions: Global health progress in psoriasis together with inequality in the past few decades. Although the inequality of psoriasis burden has shown some improvement during the past 27 years, disparities still exist in age, gender, geographical location, as well as socioeconomic status. The findings of this study highlight the global importance of psoriasis and is important in policy planning for psoriasis services on a global scale.

Abstract is missing (Short Communication)

Juvenile generalized pustular psoriasis is a rare, severe type of psoriasis that can be life-threatening. Thus far, treatment for juvenile generalized pustular psoriasis has been challenging, and no standardized guidelines are available. Here, we describe two Chinese boys with juvenile generalized pustular psoriasis who were successfully treated with infusions of infliximab. During 12 months of follow-up, no recurrence or exacerbation was observed in either patient. Herpes zoster was observed as an adverse effect in one patient, following the initial infusion of infliximab; the other patient did not experience any adverse reaction. Although infliximab is effective therapy for patients with juvenile generalized pustular psoriasis, there is a need for close monitoring of adverse effects in these patients.

Acute generalized exanthematous pustulosis, characterized by subcorneal or superficial intraepidermal pustules, is induced by drugs in more than 90% of cases. Psoriasis is an autoimmune disease triggered by different conditions in genetically susceptible people. Generalized pustular psoriasis is an acute and severe clinical form of psoriasis, which usually occurs in patients with psoriasis undergoing aggravating factors. In this report the authors have reported a 40-year-old male patient with primary syphilis who developed generalized pustular dermatosis after the use of ceftriaxone. On the third day after ceftriaxone treatment, complete regression of the syphilis lesions was reached. While on the sixth day, erythematous pustular lesions accompanied with fever were observed on the whole body. A personal history of psoriasis and histopathological findings with psoriasiform changes and subcorneal pustule favored the diagnosis. After discontinuation of ceftriaxone, the patient’s condition slowly improved until he had plaque-type psoriasis 3 weeks later. A heterozygous c.115 + 6T>C missense substitution of IL36RN related to the pathogenesis of acute generalized exanthematous pustulosis/generalized pustular psoriasis was identified.

Background/Aims: Psoriasis is a common inflammatory skin disease of undetermined etiology and poor prognosis. The current therapies have focused on direct inhibition of local inflammation, e.g. through hormone treatments. However, neovascularization plays a critical role in the development of psoriasis but so far no therapies have been developed to suppress psoriasis-associated neovascularization. Methods: We treated AGR129 mice that had received human PN skin grafts with different doses of Ginsenoside Rh2 (GRh2). The acanthosis and papillomatosis index were evaluated. The percentage of T lymphocytes in the grafts was quantified by flow cytometry. The levels of vascularization in the grafts were quantified based on CD31-positive area. We examined the levels of VEGF-A in the skin treated with GRh2. We treated AGR129 mice that had received human PN skin grafts with different doses of soluble Flt-1 (sFlt1) and then evaluated the effects on the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density. Results: GRh2 dose-dependently decreased the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density in PN skin grafts in mice. GRh2 inhibited VEGF-A levels in the PN skin grafts. Treatment with sFlt1 mimicked the effects of GRh2 on the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density in PN skin grafts in mice. Conclusions: GRh2 may have an anti-psoriasis effect through neovascularization suppression.

Nonalcoholic fatty liver disease (NAFLD) has been found to be highly prevalent in psoriatic patients. Adult onset psoriasis could be divided into either early or late onset psoriasis. The associations between NAFLD and related metabolic comorbidities and age at onset of psoriasis have not yet been investigated. Our study was to evaluate the associations between prevalence of NAFLD and related metabolic conditions and early, late, and childhood onset psoriasis. A cross-sectional observational study was conducted on patients with moderate to severe plaque psoriasis. Data on clinical characteristics of NAFLD and related metabolic diseases (diabetes, hypertriglyceridemia, hyperuricemia, and metabolic syndrome) were collected. The prevalence of NAFLD in 439 patients (mean: 51±14 years, range: 18-85 years) was 55.8%. NAFLD was frequently identified in early onset patients (74.2%), and this diagnosis was particularly common in patients currently younger than 40 (85.3%). Diabetes was the least prevalent component of metabolic syndrome in early onset patients with metabolic syndrome but the most often found component in late onset ones. Patients with childhood onset psoriasis had the lowest frequencies of all metabolic comorbidities except hyperuricemia among the three groups. In the multivariate analyses, early onset was independently and positively associated with NAFLD, hypertriglyceridemia and hyperuricemia and independently and negatively associated with diabetes among early and late onset patients. The results suggested prevalence of NAFLD and related metabolic comorbidities was associated with age at onset of moderate to severe plaque psoriasis. Early onset of psoriasis was independently associated with greater odds of NAFLD, hypertriglyceridemia, hyperuricemia and smaller odds of diabetes compared to late onset. Early onset patients have metabolic syndrome mainly related to lipid disorders and abnormal glucose metabolism was not often involved.

BMP9, a member of the TGF-ß superfamily, reveals the great translational promise for it has been shown to have the strong effect of osteogenic activity in vitro and in vivo. However, the implantation of certain BMPs (bone morphogenetic proteins) into muscular tissues induces ectopic bone formation. BMPs induce osteoblastic differentiation in skeletal muscle, suggesting that myogenic stem cells, such as myoblasts, are the potential progenitors of osteoblasts during heterotopic bone differentiation. Here, we investigate the role of BMP9 during primary mouse myoblasts differentiation. We found BMP9 enhanced cell proliferation and reduced myogenic differentiation of primary mouse myoblasts. In addition, adenovirus-mediated overexpression of BMP9 delayed muscle regeneration after BaCl 2 -induced injury. ALK1 knockdown reversed the inhibition of myoblast differentiation induced by BMP9. Our data indicate that BMP9 inhibits myogenic differentiation in primary mouse myoblasts and delays skeletal muscle regeneration after injury. BMP9 prevents myogenic differentiation partly through ALK1-Smad1/5/8 signaling. [ABSTRACT FROM AUTHOR]

The article describes the case of a 26-year old man with progressive primary cutaneous nocardiosis. The patient was treated with isoniazid, rifampicin, pyrazinamide and ethambutol but had to stop antibiotic treatment because of elevated aminotransferase and aspartate aminotransferase levels. He tested positive for hepatitis B surface antigen and e antigen, hepatitis B core antibody and serum concentration of hepatitis B virus DNA. He was later treated with oral trimethoprim-sulfamethaxazole.