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Abstract Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile. Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Abstract. Background:. Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. Methods:. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Results:. Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P

Abstract Introduction Ixekizumab, a monoclonal antibody against interleukin-17A, demonstrated effectiveness in the treatment of psoriasis in a Chinese real-world study that was consistent with previous randomized controlled trials. Here, we report further analyses from this study to explore the effectiveness of ixekizumab for treating patients with psoriasis and the involvement of special body areas (scalp, nail, joint, palmoplantar, or genital areas). Methods A multicenter, prospective, observational, single-arm, post-marketing surveillance study was conducted in patients aged ≥ 18 years with moderate-to-severe plaque psoriasis and prescribed with ixekizumab in 26 Chinese hospitals. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were compared between patients with versus without psoriasis in special body areas in the overall study population and across subgroups by body area. Results In total, 612 patients were included. At baseline, most patients (93.6%) had psoriasis involvement in at least one special body area. Overall, patients with psoriasis in special body areas reported a worse quality of life (QoL) than those without. Patients with versus without psoriasis in special body areas achieved a comparable mean reduction from baseline in PASI score (10.9 vs. 9.2 at week 2, and 16.9 vs. 14.7 at week 12, respectively) and DLQI score (6.0 vs. 4.4 at week 2, and 9.9 vs. 7.5 at week 12, respectively); a similar proportion of patients also achieved PASI 50 at week 2, and PASI 75 and PASI 90 at week 12, and a DLQI (0/1) at weeks 2 and 12. Several significantly different results were reported between subgroups, the majority of which favored patients with special body area involvement. Conclusion Most patients had psoriasis involvement in a special body area which was associated with worse QoL. Ixekizumab is similarly effective in reducing disease severity and improving QoL in patients with plaque psoriasis across different special body areas.

Abstract Introduction In vitro and pre-marketing clinical data have shown the healing properties of a postbiotic extract from Aquaphilus dolomiae (ADE-G2). The effectiveness and tolerability of an ADE-G2-based cream were therefore evaluated for the management of minor skin impairment and wound healing in a large population of subjects in routine clinical practice. Methods A real-world, international, pre-post comparative study was conducted in infants, children, and adults with various types of superficial skin impairment who used the study product daily for around 3 weeks according to their dermatologist’s advice. Immediate and follow-up changes in dermatologic signs and symptoms were assessed through clinical scoring. User satisfaction, overall product effectiveness, and tolerability were also evaluated. Analyses were performed in the whole study population and in subject subgroups according to skin impairment type and age. Results Overall, 1317 subjects (83.1% adults, 72.0% female) were included. Dermatologists reported effectiveness and “good” or “very good” tolerability of the cream in 93.8% (1221/1302) and 98.5% (1278/1297) of subjects, respectively. Immediate symptom relief after the first application was reported by 88.3% (849/962) of subjects. After several weeks of regular use (16.7 ± 11.6 days), dermatologic signs and symptoms significantly improved in the whole study population and in the subgroups, with mean decreases in severity scores ranging from –34.5% to –92.5% (p 95%) were “very satisfied” or “satisfied” with the cream and found that skin healing was rapid and of good quality. Conclusion The ADE-G2-based cream proved to be effective and well tolerated in real-life conditions for the management of minor skin impairment in a large and varied cohort of subjects. This product, used as a standalone or adjunctive regimen, can help accelerate the healing of various types of superficial skin impairment.

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.

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.

Abstract Background Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. Objective This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. Methods A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. Results The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670–0.773) and validation cohort (AUC, 0.715; 95% CI 0.665–0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. Conclusions This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .

Psoriasis is a chronic inflammatory skin disease characterized by skin infiltration of immune cells and abnormal epidermal thickening. The initial pathogenesis has not been fully elucidated. Non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs) and circular RNAs (circRNAs), comprise the majority of genome transcripts and are important influencers of gene transcription and post-transcription modulations. Emerging roles of ncRNAs in psoriasis were identified recently. This review summarizes the existing studies of psoriasis-related lncRNAs and circRNAs. A considerable proportion of the studied lncRNAs and circRNAs regulate keratinocyte mobility, such as keratinocyte proliferation and differentiation. Some lncRNAs and circRNAs are tightly related to keratinocyte inflammation reactions. Other reports demonstrated that they are also implicated in modulating immune cell differentiation, proliferation, and activation. This review might illuminate future psoriasis research and highlight that lncRNAs and circRNAs might act as therapeutic targets.

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.

BackgroundFatty liver disease (FLD) is a common comorbidity of psoriasis and is often referred to as non-alcoholic fatty liver disease (NAFLD). However, the role of inflammation or insulin resistance (IR) in FLD is inconclusive. The study aims to explore whether FLD in psoriasis patients is more related to insulin resistance or systemic inflammation level.MethodsData for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation Cohort, a prospective cohort that examines psoriasis characteristics in the Chinese population. IR was assessed using the triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) indicators. Systemic non-specific inflammation was assessed using the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII).ResultsThe analysis included a total of 647 patients. Subsequent logistic regression analysis revealed that NLR, dNLR, and SII were not significantly associated with FLD in psoriasis patients, while TyG and TyG-BMI showed significant associations with FLD. Subgroup analysis indicated that in the majority of subgroups, TyG and TyG-BMI were significantly associated with FLD, particularly TyG-BMI. Excluding individuals with methotrexate and acitretin resulted in consistent findings with the main analysis. Further analysis revealed a significantly higher diagnosis rate of metabolic-associated fatty liver disease (MAFLD) compared to NAFLD.ConclusionsMetabolic factors play a crucial role in FLD in patients with psoriasis, and TyG and TyG-BMI are potential predictors of FLD. Therefore, MAFLD can be recommend as a term to describe FLD in psoriasis patients.Trial registrationhttps://www.chictr.org.cn/showproj.html?proj=58256, identifier ChiCTR2000036186. A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population. Registered 31 August 2020.

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 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.

BackgroundPsoriasis is a chronic inflammatory skin disease with effects that extend beyond the skin. Insulin resistance (IR) has been associated with psoriasis, but it remains unclear how indicators related to the triglyceride glucose (TyG) index, which were associate with IR, are associated with the condition.ObjectiveThe purpose of this study was to investigate the association between psoriasis and three TyG-related indicators: triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), and triglyceride glucose-waist circumference (TyG-WC).MethodsData from adults aged 20 to 80 years in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006 and 2009 to 2014 were utilized. Institutional Review Board approval and documented written consent was obtained from participants by NHANES (Protocol #2005–06). The patients were divided into three groups based on TyG-BMI, TyG-WC, and TyG-WHtR: Q1 (1st quintile), Q2 (2nd-3rd quintiles), and Q3 (4th-5th quintiles). Differences between the groups were further explored. Multivariate logistic regressions were used to investigate the correlation between these three indicators and psoriasis, with results expressed as odds ratios (OR) and 95% confidence intervals (CI). Subgroup analysis and supplementary analysis was further conducted to explore potential influencing factors.ResultsThe study included 9,291 participants, of which 260 had psoriasis. Compared Q2 and Q3 of TyG-BMI, TyG-WC, and TyG-WHtR to Q1, there were significantly associate with psoriasis. Among the three indicators, TyG-WC consistently had the highest OR values in Models 1 and 2 (Model 1: Q3 OR (95% CI) = 2.155 (1.442-3.220); Model 2: Q3 OR (95% CI) = 2.029 (1.341-3.069)). While in Model 3, the TyG-BMI shows more significant relationship with psoriasis (Model 3 of TyG-BMI: Q3 OR (95% CI) = 1.948 (1.300-3.000)). Similar results were observed in the majority of subgroups and in supplementary analysis.ConclusionThis study identified a stable and strong positive association between TyG-related indicators (TyG-BMI, TyG-WC, and TyG-WHtR) and psoriasis. This association persisted even after adjusting for multiple factors. It is suggested that high IR is significantly associated with psoriasis.

Background: In recent years, biologics targeting key cytokines and Janus kinase (JAK) inhibitors have demonstrated favorable efficacy and safety outcomes for atopic dermatitis (AD) therapy. To evaluate the short-term efficacy and safety of AD therapy involving biologics, JAK inhibitors, and their combination with topical corticosteroids (TCS) for patients with AD, we conducted this systematic review and meta-analysis. Using eligible randomized clinical trials (RCTs) of 12 or 16 weeks of treatment with systemic medications and 4 weeks of topical treatment for AD. Methods: PubMed, Web of Science, ScienceDirect, and the Cochrane Library were searched from inception up to October 25, 2023. English-language randomized clinical trials (RCTs) of 12 or 16 weeks of treatment with systemic medications and 4 weeks of topical treatment for AD were included. Titles, abstracts, and articles were screened in duplicate. Of 7261 citations, 37 studies were included. The data were analyzed using Review Manager 5.4 and the outcomes were measured by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), the pruritus Numerical Rating Scale (NRS), as well as instances of adverse events (AE), and serious AE (SAE), which were presented as risk ratio (RR) with a 95 % confidence interval (CI). The efficacy of the biological therapies was analyzed with the percentage of patients who have achieved EASI 75, EASI 90, IGA 0/1 and pruritus NRS4, while the safety of treatments was evaluated in terms of the number of patients who had ≥1 AE and who had at least one SAE. Results: A total of 37 studies with 43 cohorts that examined 9 medications and placebo and involved 18172 participants were included. Compared with the placebo, all biologics and JAK inhibitors were associated with a higher response rate in efficacy outcomes, while systematic administration was presented by dupilumab 200 mg subcutaneously every 2 weeks with superior improvement in EASI 90 (RR 9.50, 95 % CI 2.31–39.03) and IGA0/1 (RR 17.00, 95 % CI 2.33–123.78), upadacitinib 30 mg once daily in EASI 75 (RR 5.14, 95 % CI 4.20–6.31) and Pruritus NRS4 (RR 5.73, 95 % CI 4.44–7.39), and external use was presented by ruxolitinib 1.5 % twice daily orally in EASI 75 (RR 4.14, 95 % CI 3.06–5.61) and Pruritus NRS4 (RR 4.08, 95 % CI 2.86–5.81), and most of doses led to a better safety profile. Most doses of baricitinib, dupilumab, tralokinumab, and upadacitinib in combination with TCS demonstrated good efficacy as compared with the control groups (placebo + TCS). However, patients receiving baricitinib at a dosage of 2 mg daily (RR 1.23, 95 % CI 1.02–1.49) and 4 mg daily (RR 1.39, 95 % CI 1.22–1.58) in combination with TCS, exhibited a higher incidence of one or more SAE as compared with those taking placebo + TCS. Conclusion: Our research has revealed that ruxolitinib and dupilumab are effective and safe treatments for mild to moderate AD and moderate to severe AD, respectively. Additionally, the combination of dupilumab and TCS demonstrates greater efficacy and safety compared to baricitinib, tralokinumab, and upadacitinib with TCS as a background treatment for moderate to severe AD. We suggest that the use of topical JAK inhibitors could be a potential alternative to TCS when used in combination with systemic medications, as a novel approach to treat AD. Insufficient different data sources caused by partial interventions were only mentioned in a few articles and low event rates in safety analyses may lead to the results being biased. Further studies directly comparing existing and novel treatments are needed and will be included in forthcoming updates of this review. Our findings could form a useful foundation for developing a new generation of treatment guidelines for AD.

BackgroundPsoriasis is a chronic skin disease affecting approximately 3.2% of the population. The 308 nm light emitting diode (LED) is a novel, portable, and cost-effective light source, may have potential in the treatment of localized psoriasis patients in a home setting.ObjectiveTo compare the clinical and dermoscopic responses in localized psoriatic patients undergoing localized phototherapy with 308 nm LED light and excimer laser.MethodsTwenty-two patients with mild-to-moderate psoriasis and symmetrical skin lesions were included in this prospective, randomized, left-to-right body trial. The target lesions were randomly treated with either LED light or excimer laser twice a week for 12 weeks. The responses were evaluated by the local psoriasis severity index (LPSI) scores, and dermoscopic features of the target lesions were examined and analyzed.ResultsOut of the 22 included psoriasis patients, 10 successfully completed the 12 weeks study. Both treatment sides showed similar clinical improvement in terms of clinical response, as evidenced by a LPSI 50 rate of 70% on the LED side and 80% on the excimer side, p > 0.05. Furthermore, the dermoscopic features also exhibited comparable improvement.ConclusionThe efficacy and safety of 308 nm LED light therapy are comparable to 308 nm excimer laser therapy. Moreover, given the portability and cost-effectiveness of 308 nm LED light, it holds great promise as a home phototherapy in the treatment of psoriasis.

BackgroundPsoriasis is a chronic and refractory skin disease. The emergence of biologics provides more options for the treatment of psoriasis, but the COVID-19 pandemic poses challenges for the management of psoriasis.ObjectivesThe purpose of this study was to investigate the effect of different biologics on the stabilization of psoriasis during COVID-19 infection in China.MethodsThis is a single-center, observational, retrospective, case–control study. Using our database, we conducted a remote dermatologic study by means of questionnaire follow-up or telephone follow-up to collect general information of patients, information related to COVID-19 infection and conditions of psoriasis for comparison and further analysis between groups.ResultsOur study ultimately included 274 patients for analysis. We found that the patients in this collection had mild symptoms of COVID-19 infection, and only 13 of them needed to go to the hospital for medical treatment. Further studies found that in biologics, relative to tumor necrosis factor-α inhibitors (TNF-αi), interleukin-17 inhibitors (IL-17i) and interleukin-23 inhibitors (IL-23i) are both protective factors in flare-up of psoriasis [IL-17i: OR (95% CI) = 0.412 (0.189–0.901); IL-23i: OR (95% CI) = 0.291 (0.097–0.876)]. In addition, we also found that the proportion of people with increased psoriasis developing long COVID-19 increased, and we speculated that increased psoriasis may be a potential risk factor for long COVID-19.ConclusionOur study showed that the use of IL-17i and IL-23i was a protective factor for psoriasis compared with TNF-αi, and could keep the psoriasis stable.

Due to the lack of drilling data in the Zhu 1 Depression of the Pear River Mouth Basin, the Enping 17 Sag is taken as an example in this paper to solve the problem of comprehensive identification of underground distribution of high-quality source rocks. Based on the analysis of the geological background, sedimentary characteristics and petrophysical characteristics of source rocks, seismic inversion is guided by the constraints of the petrophysical characteristics of the source rocks in different sedimentary environments. According to the statistics of the relationship between the lithofacies of drilled source rocks and the inversion resistance, a semi-quantitative prediction of the spatial distribution of favorable source rocks is made by geological modeling, and the rationality of prediction method and results is analyzed in combination with the recognition of the geochemical origin type and source of crude oil, to discuss the geological and geophysical identification method of the underground distribution of high-quality source rocks with lack of drilling data. The more reductive the depositional environment of source rocks in the Paleogene Wenchang Formation, the lower the impedance value of high-quality source rocks, and the greater the impedance difference between poor source rocks or non-source rocks. The third, fourth and fifth members of Wenchang Formation are the main source rocks of the Enping 17 Sag, which can be supported by the study of crude oil biomarkers. In the small sags of the Pearl River Mouth Basin with basically clear petroleum geological background conditions, establishing the quantitative and semi-quantitative relationship between the lithofacies of source rocks and the inversion impedance value is helpful to quickly clarify the development interval and scale of main source rocks. This method has a good prospect of popularization and application.

Abstract RNA modifications have become hot topics recently. By influencing RNA processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune cell abnormality in human diseases is also a research focus and progressing rapidly these years. Studies have demonstrated that RNA modifications participate in the multiple biological processes of immune cells, including development, differentiation, activation, migration, and polarization, thereby modulating the immune responses and are involved in some immune related diseases. In this review, we present existing knowledge of the biological functions and underlying mechanisms of RNA modifications, including N 6-methyladenosine (m6A), 5-methylcytosine (m5C), N 1-methyladenosine (m1A), N 7-methylguanosine (m7G), N 4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, and adenosine-to-inosine (A-to-I) RNA editing, and summarize their critical roles in immune cell biology. Via regulating the biological processes of immune cells, RNA modifications can participate in the pathogenesis of immune related diseases, such as cancers, infection, inflammatory and autoimmune diseases. We further highlight the challenges and future directions based on the existing knowledge. All in all, this review will provide helpful knowledge as well as novel ideas for the researchers in this area.

Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred treatment for AIBD involves the use of glucocorticoids or traditional immunosuppressants. Additionally, the utilization of biological agents such as rituximab, omalizumab, and dupilumab is on the rise. However, effectively managing AIBD remains a challenge. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway has been implicated in various inflammatory diseases. In recent years, a range of drugs known as JAK inhibitors, which target this pathway, have been developed. Several studies have explored the efficacy and safety of JAK inhibitors for treating AIBD. Consequently, this review begins by examining the role of the JAK/STAT pathway in AIBD, summarizing the application of different JAK inhibitors in AIBD treatment, and emphasizing the importance of disease management in treating AIBD with JAK inhibitors. Furthermore, it highlights the need for a better understanding of the JAK/STAT pathway’s role in AIBD, as well as the effectiveness and safety of JAK inhibitors for treating this disease.

Ustekinumab is a biological therapy that has been approved for treating moderate-to-severe psoriasis. Although injection site reactions, nasopharyngitis, headaches, and infections are the common adverse events associated with ustekinumab, the development of bullous pemphigoid (BP) is also thought to be related to ustekinumab. Given that psoriasis itself can be complicated by BP, it is worthwhile to investigate the relationship between ustekinumab, psoriasis, and BP. Here we report a case of a male patient who developed BP twice after psoriasis treatment with ustekinumab. The patient’s psoriasis and BP were brought under control by discontinuing ustekinumab and administering methotrexate, minocycline, and topical corticosteroids. Because of the increasing use of biologics in patients with psoriasis, BP should be considered a potential adverse event associated with ustekinumab.

To reduce the erosion of the loess slope under the condition of rainstorms, the loess cured by guar gum is used to protect the slope surface. The engineering properties and erosion resistance of the guar gum-reinforced loess are studied by conducting the direct shear test, penetration test, slope scour test in simulated rainstorm, and the curing mechanism of guar gum is studied by contrasting the microstructure characteristics of plain loess and reinforced loess. The results show that the guar gum can effectively enhance the shear strength and the anti-permeability of loess. The cohesion and internal friction angle of the reinforced loess show the same trend, and they increase first and then decrease with the increasing guar gum content, and increase with the increasing curing age. The saturated permeability coefficient decreases with the increasing guar gum content and curing age. Compared with plain loess, the cohesion and internal friction angle of 7 d cured loess with 1.0% guar gum content increases by 53.7% and 5.6%, and the saturated permeability coefficient decreases by 78.3%. The slope protection effect of the guar gum-reinforced loess under rainstorm scour condition is obvious. Compared with the slope without protection, the cumulative scour amount of the slope decreases by 64.4%, and the average slope flow rate increases by 55.2%. The strengthening mechanism of guar gum on loess mainly lies in the high viscosity hydrogel produced by its hydration reaction to fill the pores and cement loess particles. This study provides test support for the application and promotion of the guar gum-reinforced loess in slope protection engineering.

The use of immune checkpoint inhibitors (ICIs) targeting the T cell inhibitory pathways has revolutionized cancer treatment. However, ICIs might induce progressive atopic dermatitis (AD) by affecting T cell reactivation. The critical role of T cells in AD pathogenesis is widely known. T cell co-signaling pathways regulate T cell activation, where co-signaling molecules are essential for determining the magnitude of the T cell response to antigens. Given the increasing use of ICIs in cancer treatment, a timely overview of the role of T cell co-signaling molecules in AD is required. In this review, we emphasize the importance of these molecules involved in AD pathogenesis. We also discuss the potential of targeting T cell co-signaling pathways to treat AD and present the unresolved issues and existing limitations. A better understanding of the T cell co-signaling pathways would aid investigation of the mechanism, prognosis evaluation, and treatment of AD.

Abstract Psoriasis is a complex long-lasting inflammatory skin disease with high prevalence and associated comorbidity. It is characterized by epidermal hyperplasia and dermal infiltration of immune cells. Here, we review the role of keratinocytes in the pathogenesis of psoriasis, focusing on factors relevant to genetics, cytokines and receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, and proteins with other different functions. The critical role of keratinocytes in initiating and maintaining the inflammatory state suggests the great significance of targeting keratinocytes for the treatment of psoriasis.

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.

Background and purposeAcupuncture is widely used in clinical practice for the treatment of vascular diseases. However, the protocol, efficacy, and mechanism of acupuncture in animal models of vascular dementia are still controversial. Based on the above problems, we initiated this comprehensive study.MethodsTo analyze the literatures included in this study, 4 databases were searched and the SYRCLE's Risk of bias tool was employed. To perform the subgroup analysis of different acupuncture methods and the Review Manager 5.3 was applied. Meanwhile, the pairwise and network meta-analysis were conducted using Addis 1.16.8. The outcomes included escape latency, number of crossings, time spent in the target quadrant, and swimming speed.ResultsForty-two studies with a total of 1,486 animals were included in this meta-analysis. According to the results from subgroup analysis, GV20 + ST36 (Baihui + bilateral Zusanli) combined with 14-day manual acupuncture can obtain best improvement of the rats cognitive function among all acupuncture regimens (MD: −23.41; 95%CI: −26.66, −20.15; I2 = 0%; P < 0.001). The heterogeneity of other acupuncture treatments was significantly higher than that of GV20 + ST36, because the treatment courses were not uniform. Pair-wise and network comparisons are highly consistent. The major results of the network meta-analysis were as follows, In comparison to the impaired group, the acupuncture group showed significantly reduced escape latency (MD: −25.87; 95%CI: −30.75, −21.12), increased number of original platform crossings (MD: 2.63; 95%CI: 1.94, 3.34) and time spent in the target quadrant (MD: 7.88; 95%CI: 4.25, 11.44). The overall results of the network meta-analysis are as follows: the normal and sham-operated groups performed the best, followed by medicine and acupuncture, while no effect was found in the impaired group treated with non-acupoint and palliative.ConclusionsAcupuncture significantly improves cognitive function in rats with vascular dementia. Compared to other acupuncture plans, (GV20 + ST36, MA) and 14 -day manual acupuncture can be used to obtain better results. The main mechanism of acupuncture in the treatment of vascular dementia is reduced oxidative stress, neuronal inflammation, and apoptosis, as well as the increased synaptic plasticity and neurotransmitters.Systematic review registrationhttps://inplasy.com/inplasy-2021-11-0036/, identifier: INPLASY2021110036.

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.

Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures lacking 5′–3′ polarity and a polyadenine tail. Over recent years, a growing body of studies have been conducted to explore the roles of circRNAs in human diseases. Systemic lupus erythematosus (SLE) is a severe autoimmune disorder characterized by the presence of autoantibodies and excessive inflammation, which impact multiple organs. Recent advances have begun to shed light on the roles of circRNAs in SLE, providing fresh insights into the pathogenesis of SLE and the latent capacity for translation into clinical applications. Here, we briefly introduce these “star molecules” and summarize their roles in SLE. In addition, we outline the limitations of the current studies and raise prospects for future research.

In order to study the mechanism and product compositions of oil cracking, crude oil samples from the Zhuhai Formation of the Baiyun Sag of Pearl River Mouth Basin were carried out for the high-temperature, high-pressure pyrolysis with different heating rates with the pressure close to the conditions of underground. The underground fluid was also considered to be included with a semi-open condition for the pyrolysis, the gas yields and gas composition characteristics were then analyzed. Results showed that crude oils start to crack at 365 ℃, and the cracking yield increases with the increase of temperature. At a heating rate of 20 ℃/h, the final yields (at 550 ℃) of pyrolysis gas, hydrocarbon gas and non-hydrocarbon gas were 580.13, 394.25, and 185.88 mg/g, while at a heating rate of 60 ℃/h, these values increased to 707.68, 485.77, 221.91 mg/g, respectively. The composition of hydrocarbon gases at different heating rates also varied, and these variations were assumed to be related to the difference of cracking mechanisms of crude oils at different temperatures of pyrolysis. According to the composition characteristics of pyrolytic gas products, most of the gases from crude oil cracking has a relative higher content of high molecular weight hydrocarbon gas, thus these compounds can be used as an auxiliary index to distinguish crude oil cracked gas from kerogen cracked gas.

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.

IntroductionTobacco smoking is associated with the onset and severity of psoriasis, and understanding the prevalence of tobacco smoking among patients with psoriasis is critical due to its high physical and mental influence and heavy disease burden. However, evidence on the association between tobacco smoking and psoriasis severity is still limited in China.ObjectivesThe objective of this study was to examine the prevalence of tobacco smoking and explore the association between tobacco smoking and diseases severity among patients with psoriasis.MethodsA total of 4,529 patients with psoriasis in 200 selected hospitals were recruited in China between January 2020 and September 2021. Detailed information covering demographic feature, tobacco smoking, and psoriasis history were collected through an electronic questionnaire, and clinical data were extracted from the health information system (HIS). SAS 9.4 was used for data analysis, and a p-value of 13, when compared with patients with PASI score < 3.0. Similarly, the OR of current tobacco smoking prevalence was 1.8 [95% CI: (1.5–2.2)] for PASI score (3.0–7.0), 1.9 for PASI score (7.1–13.0), and 3.1 for PASI score >13, when compared with patients with PASI score

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.

Background: Psoriasis is a common immune-mediated skin disease that involves T-cell-mediated immunity. Invariant natural killer T (iNKT) cells are a unique lymphocyte subpopulation that share properties and express surface markers of both NK cells and T cells. Previous reports indicate that iNKT cells regulate the development of various inflammatory diseases. IL-17 is a key cytokine in the pathogenesis of psoriasis and a key therapeutic target. Secukinumab is a fully human IgG1κ antibody that targets IL-17A, thereby antagonizing the biological effects of IL-17.Objective: To explore the expression of iNKT cells in psoriasis patients and the effect of secukinumab on them.Methods: We examined the frequencies of iNKT cells, Tregs, naïve and memory CD4+and CD8+T cells in the PBMCs as well as their cytokine production in a cohort of 40 patients with moderate-to-severe plaque psoriasis and 40 gender- and age-matched healthy controls. We further collected peripheral blood of another 15 moderate-to-severe plaque psoriasis patients who were treated with secukinumab and evaluated the proportion of iNKT cells in the PBMCs at baseline and week 12.Results: The frequencies of conventional CD4+ T cells, CD8+ T cells, and Tregs in the PBMCs were comparable between psoriasis patients and healthy controls, but the frequencies of Th17 cells, Tc1 cells and Tc17 cells were increased in psoriasis patients. The frequency of peripheral iNKT cells and CD69+iNKT cells was significantly decreased in psoriasis patients. Both iNKT2 cells and iNKT17 cells were increased in psoriasis patients, but the ratio of iNKT2 cells vs iNKT17 cells was significantly reduced in psoriasis patients. After receiving secukinumab, the proportion of iNKT cells in the PBMCs of patients was increased, while the proportion of iNKT17 cells was decreased.Conclusion: Dysregulated iNKT cells may be involved in the pathogenesis of psoriasis and secukinumab may play a regulatory role on iNKT cells.

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

Psoriasis is a chronic inflammatory disease characterized by erythematous scaly plaques, accompanied by systemic damage that leads to the development of multiple comorbidities. In particular, the association between psoriasis and cardiometabolic comorbidities, including cardiovascular diseases (CVDs), obesity, diabetes mellitus, and metabolic syndrome, has been verified in a considerable number of clinical trials. Moreover, the increased risk of cardiometabolic comorbidities positively correlates with psoriasis severity. Biologic therapy targeting inflammatory pathways or cytokines substantially improves the life quality of psoriasis patients and may affect cardiometabolic comorbidities by reducing their incidences. In this review, we focus on exploring the association between cardiometabolic comorbidities and psoriasis, and emphasize the benefits and precautions of biologic therapy in the management of psoriasis with cardiometabolic comorbidities. The pathogenic mechanisms of cardiometabolic comorbidities in psoriasis patients involve common genetic factors, lipid metabolism, insulin resistance, and shared inflammatory pathways such as tumor necrosis factor-α and interleukin-23/Th-17 pathways.

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: Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4+ T cells (Th17) and repressed regulatory T (Treg) cells. IL-21 is a Th17-related cytokine and plays an important role in the pathogenesis of psoriasis. However, the mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood.Methods: IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immumohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-10 in the culture supernatants was measured by cytometric bead array (CBA). The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). CD4+ T cells were isolated from the peripheral blood mononuclear cells (PBMCs) from the psoriasis patients and healthy individuals and then treated with or without IL-21 for 3 days. The proportions of Th17 and Treg cells were determined by flow cytometric analysis.Results: IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of psoriasis patients. IL-21 promoted CD4+ T cells proliferation and Th17 cells differentiation and inhibiting Treg cells differentiation by upregulating RORγt expression and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22. The proportion of Treg cells was negatively correlated with that of Th17 cells in psoriasis patients.Conclusion: Our results suggest that IL-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations.

The loess slope in east Gansu presents a large degree of anisotropy which should be considered both in the slope stability analysis and in the reinforcement design. To investigate the mechanical anisotropy presented in the loess soil, the undisturbed loess specimens are taken from the field with different sampling directions (α, defined as the angle between the normal direction of specimen and sedimentation direction). The direct shear tests are conducted on specimens of different α, and it is found that the anisotropy has slight influence on the friction angle (φ), while the specimen with α=0° presents the smallest cohesion and the specimen with α=90° has the largest cohesion. The anisotropy behaviors have also been observed from the one-dimensional consolidation test and tension test. After that, the principle of point safety factor and the degree of reinforcement demand are introduced, and the method of quantitative reinforcement of anisotropic loess slope is proposed. The proposed approach is then implemented in the Fast Lagrangian Analysis of Continua in 3D (FLAC3D), and the point safety factor and the degree of reinforcement demand are investigated on slope with different slope ratios. It is found that the proposed approach could effectively be used to analyze the slope involving anisotropy through the comparison with the conventional limit equilibrium method. Meanwhile, the reinforcement zone and the reinforcement demanding of anisotropy slope are obtained, and relevant reinforcement design in practice is proposed.

Background/Aims: Autosomal-dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder caused by mutations in the PKD1 and PKD2 genes. Currently, long-range PCR followed by nested PCR and sequencing (LRNS) is the gold standard approach for PKD1 testing. However, LRNS is complicated by the high structural and sequence complexity of PKD1, which makes the procedure for amplification and analysis of PKD1 difficult. Methods: Here in, we modified the PCR conditions and designed primers for efficient and specific amplification of both the long-range and individual exons of PKD1. Results: Using the modified system, seven long-range fragments were specifically amplified using two distinct sets of conditions, and all individual exon PCR assays were easily performed using a touch-down PCR method. Seven pathogenic or likely pathogenic variants, including two novel truncated frameshift indels and two novel likely pathogenic missense mutations, were identified in eight unrelated patients with or without histories of ADPKD disease (one variant was observed in two unrelated patients). Using combined bioinformatics tools, two indeterminate missense variants were identified in two sporadic patients. Conclusion: Four novel PKD1 variants were identified in this study. We demonstrated that the modified LRNS method achieves high sensitivity and specificity for detecting pathogenic variants of ADPKD.

Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV). α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A) is an ω-oxidase that inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD) maps of these two genes were built with Haploview using data on CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51); rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95% CI 1.10-3.68). To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30-2.04) was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37-2.09). The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS development.