Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

A Building Extraction Method for High-Resolution Remote Sensing Images with Multiple Attentions and Parallel Encoders Combining Enhanced Spectral Information.

Accurately extracting pixel-level buildings from high-resolution remote sensing images is significant for various geographical information applications. Influenced by different natural, cultural, and social development levels, buildings may vary in shape and distribution, making it difficult for the network to maintain a stable segmentation effect of buildings in different areas of the image. In addition, the complex spectra of features in remote sensing images can affect the extracted details of multi-scale buildings in different ways. To this end, this study selects parts of Xi'an City, Shaanxi Province, China, as the study area. A parallel encoded building extraction network (MARS-Net) incorporating multiple attention mechanisms is proposed. MARS-Net builds its parallel encoder through DCNN and transformer to take advantage of their extraction of local and global features. According to the different depth positions of the network, coordinate attention (CA) and convolutional block attention module (CBAM) are introduced to bridge the encoder and decoder to retain richer spatial and semantic information during the encoding process, and adding the dense atrous spatial pyramid pooling (DenseASPP) captures multi-scale contextual information during the upsampling of the layers of the decoder. In addition, a spectral information enhancement module (SIEM) is designed in this study. SIEM further enhances building segmentation by blending and enhancing multi-band building information with relationships between bands. The experimental results show that MARS-Net performs better extraction results and obtains more effective enhancement after adding SIEM. The IoU on the self-built Xi'an and WHU building datasets are 87.53% and 89.62%, respectively, while the respective F1 scores are 93.34% and 94.52%.

Smart Use of Skin Biopsy Punch in Treating Keloids: A Single-Center Retrospective Study.

BACKGROUND: Treatment of scarring has long been a problem due to high incidence and recurrence. Despite many existing treatment therapies, the efficacy remains unstable. OBJECTIVES: To determine the efficacy and safety of skin biopsy punch in combination with corticosteroid injection (BPCI) in treating keloids. APPROACH: This was a retrospective study. In total, 16 patients with keloids received BPCI. Changes in scar appearance, accompanied symptoms, and Vancouver Scar Scale (VSS) were analyzed. Patient satisfaction, VAS scores, and adverse effects were also evaluated. RESULTS: Scar appearance, accompanied symptoms, and VSS scores improved significantly after the treatment. The total effective rate was 93.75% at an 18-month follow-up on average. The mean reduction rate of VSS score was 58.44% (p < 0.0001), especially in height and pliability (84.44% and 78.19%, p < 0.0001). The recurrence rate in this study was 12.5% (n = 2) at an 18-month follow-up on average. Mild adverse effects of pain, pruritus, hypopigmentation, and telangiectasia were recorded. CONCLUSIONS: This study demonstrated BPCI might be an effective and safe therapy in keloids with a low long-time recurrence rate and well tolerance for patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Regulatory mechanisms of mitochondrial dynamics and its emerging role in renal pathophysiology].

Mitochondria are dynamically changing organelles that maintain stable mitochondrial morphology, number, and function through constant fusion and division, a process known as mitochondrial dynamics, which is an important mechanism for mitochondrial quality control. Excessive fusion and division of mitochondria can lead to a homeostatic imbalance in mitochondrial dynamics, causing mitochondrial dysfunction, leading to cellular damage, and even death. The physiological functions of the kidney are mainly powered by mitochondria, and homeostatic imbalance in mitochondrial dynamics affects mitochondrial function and is closely related to renal diseases such as acute kidney injury and diabetic nephropathy. This article reviews the regulation of mitochondrial kinetics, how imbalances in mitochondrial kinetic homeostasis affect mitochondrial injury, and the impact of mitochondrial injury on renal pathophysiology, in order to improve understanding and knowledge of the role of mitochondria in renal disease.

Lipidomic profiling reveals metabolic signatures in psoriatic skin lesions.

Psoriasis is a chronic immune-mediated inflammatory disease. Lipids play an important role in regulating the inflammatory response. However, the alteration of lipids involved in psoriasis particular in skin lesions remain unclear. Here, we performed the lipidomics to investigate lipid profiling in the skin lesions of the imiquimod-induced psoriasis-like dermatitis and psoriasis patients. The findings showed that ceramides phosphate (CerP) and ceramides were enriched in psoriatic lesions compared with controls from both psoriasis patients and psoriasis-like mouse model. Psoriasis patients were classified into two subtypes, the CC1 and CC2, by consensus clustering of these lipid signatures. The CC1 was characterized by the higher levels of CerP, uric acid, and more severe psoriasis, compared with CC2 subtype. Interestingly, ceramide-1-phosphate (C1P), dramatically enriched in CC1 subtype, facilitated imiquimod-induced psoriasis-like inflammatory responses. Mechanistically, C1P induced the expression of inflammatory factors and activated DNA replication and cell cycle signaling pathways in the primary keratinocytes. Inhibiting the production of C1P with ceramide kinase inhibitor effectively alleviated the imiquimod-induced psoriasis-like inflammation. Taken together, we described the landscape of lipids alteration and established lipids classification based on pattern of abundance of lipids in psoriatic skin lesions. Suppression of C1P pathway is a novel potential strategy for psoriasis treatment.

Adenosine 5'monophosphate-activated protein kinase activation reduces the risks of psoriasis and its comorbidities: a mendelian randomisation study in the UK Biobank.

OBJECTIVE: Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank(UKB). METHODS: To avoid immortal-time-biases in pharmacoepidemiologic studies, Mendelian randomisation was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with HbA1c, serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 407 159 participants were analyzed, including 9,126 EOP and 3,324 LOP. The AMPK-genetic-risk-score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022-1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062-1.395) in male psoriasis patients. CONCLUSIONS: AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Bardoxolone methyl inhibits the infection of rabies virus via Nrf2 pathway activation in vitro.

BACKGROUND: Rabies is a widespread, fatal, infectious disease. Several antivirals against rabies virus (RABV) infection have been reported, but no approved, RABV-specific antiviral drugs that inhibit RABV infection in the clinic after symptom onset are available. Therefore, more effective drugs to reduce rabies fatalities are urgently needed. Bardoxolone methyl (CDDO-Me), an FDA-approved compound that has long been known as an antioxidant inflammatory modulator and one of the most potent nuclear factor erythroid-derived 2-like 2 (Nrf2) activators, protects myelin, axons, and CNS neurons by Nrf2 activation. Therefore, we investigated the potency of its anti-RABV activity in vitro. METHODS: The mouse neuroblastoma cell line Neuro2a (N2a) and three RABV strains of different virulence were used; the cytotoxicity and anti-RABV activity of CDDO-Me in N2a cells were evaluated by CCK-8 assay and direct fluorescent antibody (DFA) assay. Pathway activation in N2a cells infected with the RABV strains SC16, CVS-11 or CTN upon CDDO-Me treatment was evaluated by western blotting (WB) and DFA assay. RESULTS: CDDO-Me significantly inhibited infection of the three RABV strains of differing virulence (SC16, CVS-11 and CTN) in N2a cells. We also examined whether CDDO-Me activates the Nrf2-associated pathway upon infection with RABV strains of differing virulence. Nrf2, phosphorylated sequestosome (SQSTM1), SQSTM1, hemoglobin oxygenase (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) expression in N2a cells increased to varying degrees with CDDO-Me treatment, accompanied by Kelch-like ECH-associated protein 1 (Keap1) dissociation, upon infection with SC16, CVS-11 or CTN. The activation of SQSTM1 phosphorylation was significantly associated with the degradation of Keap-1 in CDDO-Me-treated N2a cells upon RABV infection. Furthermore, N2a cells pretreated with the Nrf2-specific inhibitor ATRA showed a significant decrease in HO-1 and NQO1 expression and a decrease in the anti-RABV efficacy of CDDO-Me. These inhibitory effects were observed upon infection with three RABV strains of differing virulence. CONCLUSION: CDDO-Me inhibited RABV infection via Nrf2 activation, promoting a cytoprotective defense response in N2a cells. Our study provides a therapeutic strategy for RABV inhibition and neuroprotection during viral infection.

Lysophosphatidylcholine facilitates the pathogenesis of psoriasis through activating keratinocytes and T cells differentiation via glycolysis.

BACKGROUND: Although abnormal metabolism plays a critical role in the pathogenesis of psoriasis, the details are unclear. OBJECTIVES: Here, we identified to explore the role and mechanism of lysophosphatidylcholine (LPC) on the pathogenesis of psoriasis. METHODS: The level of LPC in plasma and skin lesions and the expression of G2A on skin lesions of psoriasis patients were detected by enzyme-linked immunosorbent assay, liquid chromatography-tandem mass spectrometry, or immunohistochemistry, respectively. The glycolysis in the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model was detected by extracellular acidification rate. LPC was subcutaneously injected into IMQ-treated mouse ears, and the phenotype as well as the glycolysis were evaluated. Exploring the effects and mechanism of LPC on keratinocytes and CD4+ T cells by culturing primary keratinocytes and CD4+ T in vitro. RESULTS: We found that LPC was significantly increased both in the plasma and skin lesions of psoriatic patients, while G2A, exerting an essential role in LPC-inducing biological functions, was increased in psoriatic lesions. The abundance of LPC was positively correlated with glycolytic activity in the psoriasis-like mouse model. LPC treatment facilitated psoriasis-like inflammation and glycolytic activity in skin lesions. Mechanistically, the LPC/G2A axis significantly triggered glycolytic activity and produced inflammatory factors in keratinocytes, and blockade of glycolysis abrogated LPC-induced expression of inflammatory mediators in keratinocytes. LPC activated STAT1, resulting in recognition and binding to the promoters of GCK and PKLR, which are glycolytic rate-limiting enzymes. Furthermore, the LPC/G2A axis directly benefited Th1 differentiation, which was dependent on LPC-induced glycolytic activity. Notably, LPC indirectly facilitated Th17 differentiation by inducing the secretion of IL-1ß in keratinocytes-T cells coculture system. CONCLUSIONS: Taken together, our findings revealed the role of the LPC/G2A axis in the pathogenesis of psoriasis; targeting LPC/G2A is a potential strategy for psoriasis therapy.

Artificial Intelligence-Based Psoriasis Severity Assessment: Real-world Study and Application.

BACKGROUND: Psoriasis is one of the most frequent inflammatory skin conditions and could be treated via tele-dermatology, provided that the current lack of reliable tools for objective severity assessments is overcome. Psoriasis Area and Severity Index (PASI) has a prominent level of subjectivity and is rarely used in real practice, although it is the most widely accepted metric for measuring psoriasis severity currently. OBJECTIVE: This study aimed to develop an image-artificial intelligence (AI)-based validated system for severity assessment with the explicit intention of facilitating long-term management of patients with psoriasis. METHODS: A deep learning system was trained to estimate the PASI score by using 14,096 images from 2367 patients with psoriasis. We used 1962 patients from January 2015 to April 2021 to train the model and the other 405 patients from May 2021 to July 2021 to validate it. A multiview feature enhancement block was designed to combine vision features from different perspectives to better simulate the visual diagnostic method in clinical practice. A classification header along with a regression header was simultaneously applied to generate PASI scores, and an extra cross-teacher header after these 2 headers was designed to revise their output. The mean average error (MAE) was used as the metric to evaluate the accuracy of the predicted PASI score. By making the model minimize the MAE value, the model becomes closer to the target value. Then, the proposed model was compared with 43 experienced dermatologists. Finally, the proposed model was deployed into an app named SkinTeller on the WeChat platform. RESULTS: The proposed image-AI-based PASI-estimating model outperformed the average performance of 43 experienced dermatologists with a 33.2% performance gain in the overall PASI score. The model achieved the smallest MAE of 2.05 at 3 input images by the ablation experiment. In other words, for the task of psoriasis severity assessment, the severity score predicted by our model was close to the PASI score diagnosed by experienced dermatologists. The SkinTeller app has been used 3369 times for PASI scoring in 1497 patients from 18 hospitals, and its excellent performance was confirmed by a feedback survey of 43 dermatologist users. CONCLUSIONS: An image-AI-based psoriasis severity assessment model has been proposed to automatically calculate PASI scores in an efficient, objective, and accurate manner. The SkinTeller app may be a promising alternative for dermatologists' accurate assessment in the real world and chronic disease self-management in patients with psoriasis.

Research on a Space-Time Continuous Sensing System for Overburden Deformation and Failure during Coal Mining.

Underground coal mining can cause the deformation, failure, and collapse of the overlying rock mass of a coal seam. If the mining design, monitoring, early warning, or emergency disposal are improper, in that case, it can often lead to mining disasters such as roof falls, water inrush, surface collapse, and ground fissures, seriously threatening the safety of mine engineering and the geological environment protection in mining areas. To ensure the intrinsic security of the entire coal mining process, aspace-time continuous sensing system of overburden deformation and failure was developed, which breaks through the limitations of traditional monitoring methods that characterize the evolution process of overlying rock deformation and ground subsidence. This paper summarizes the classification of typical overburden deformation and failure modes. It researches the space-time continuous sensing of rock-soil mass above the coal seam based on Distributed Fiber Optic Sensing (DFOS). A multi-range strain optical fiber sensing neural series from micron to meter was developed to achieve synchronous sensing of overburden separation, internal micro-cracks, and large rock mass deformation. The sensing cable-rock mass coupling test verified the reliability of the optical fiber monitoring data. The sensing neural network of overburden deformation was constructed using integrated optical fiber layout technology on the ground and underground. Different sensing nerves' performance and application effects in overburden deformation and failure monitoring were compared and analyzed with field monitoring examples. A physical model was used to carry out the experimental study on the overburden subsidence prediction during coal mining. The results showed that the optical fiber monitoring data were reliable and could be used to predict overburden subsidence. The reliability of the calculation model for overlying rock subsidence based on space-time continuous optical fiber sensing data was verified in the application of mining subsidence evaluation. A systematic review of the shortcomings of current overburden deformation observation technology during coal mining was conducted, and a space-time continuous sensing system for overburden deformation and failure was proposed. This system integrated sensing, transmission, processing, early warning, decision-making, and emergency response. Based on the fusion of multi-parameter sensing, multi-method transmission, multi-algorithm processing, and multi-threshold early warning, the system realized the real-time acquisition of space-time continuous information for the overburden above coal seams. This system utilizes long-term historical monitoring data from the research area for data mining and modeling, realizing the prediction and evaluation of the evolution process of overburden deformation as well as the potential for mining subsidence. This work provides a theoretical reference for the prevention and control of mining disasters and the environmental carrying capacity evaluation of coal development.

Novel Information-Driven Smoothing Spline Linearization Method for High-Precision Displacement Sensors Based on Information Criterions.

A noise-resistant linearization model that reveals the true nonlinearity of the sensor is essential for retrieving accurate physical displacement from the signals captured by sensing electronics. In this paper, we propose a novel information-driven smoothing spline linearization method, which innovatively integrates one new and three standard information criterions into a smoothing spline for the high-precision displacement sensors' linearization. Using theoretical analysis and Monte Carlo simulation, the proposed linearization method is demonstrated to outperform traditional polynomial and spline linearization methods for high-precision displacement sensors with a low noise to range ratio in the 10-5 level. Validation experiments were carried out on two different types of displacement sensors to benchmark the performance of the proposed method compared to the polynomial models and the the non-smoothing cubic spline. The results show that the proposed method with the new modified Akaike Information Criterion stands out compared to the other linearization methods and can improve the residual nonlinearity by over 50% compared to the standard polynomial model. After being linearized via the proposed method, the residual nonlinearities reach as low as ±0.0311% F.S. (Full Scale of Range), for the 1.5 mm range chromatic confocal displacement sensor, and ±0.0047% F.S., for the 100 mm range laser triangulation displacement sensor.

Tim-3: An inhibitory immune checkpoint is associated with maternal-fetal tolerance and recurrent spontaneous abortion.

The establishment and maintenance of pregnancy are involved in maternal-fetal immune tolerance whose imbalance can lead to recurrent spontaneous abortion (RSA). RSA is defined as two or more clinically recognized pregnancy losses within 20-24 weeks of gestation with the same partner, including embryonic and fetal losses. However, approximately half of RSA cases are idiopathic, which may be related to immune aberrations. T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is an inhibitory checkpoint protein that plays a critical role in immune tolerance. Several studies have reported that Tim-3 expression in immune cells is important for maintaining maternal-fetal immune tolerance and that the abnormal expression of Tim-3 may be associated with RSA. To further understand the etiology and pathogenesis of RSA and inspire novel strategies for its diagnosis and treatment, we reviewed the research progress on the Tim-3-induced regulation of natural killer cells, T cells, macrophages, dendritic cells, and myeloid-derived suppressor cells in maternal-fetal immune tolerance and RSA.

Lachnospira is a signature of antihistamine efficacy in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease with many advances in its aetiology and pathogenesis over the past years. The main treatment of CSU is oral second-generation antihistamines. However, only an average of 50% of CSU patients responded adequately to conventional or quadruple doses of non-sedative antihistamines. Meanwhile, gut microbiota can affect the efficacy of drugs. The purpose of this study was to investigate the relationship between gut microbiota and the efficacy of antihistamines in patients with CSU. The patients with CSU were divided into responders and non-responders according to the efficacy of antihistamine monotherapy. The gut microbiota of faecal samples from 15 responders and 15 non-responders was detected by 16S rDNA sequencing, and the differential bacterial species between the two groups were verified by quantitative polymerase chain reaction (qPCR). Additional faecal samples from 30 responders and 30 non-responders were used as an extended cohort to further verify the above differential bacterial species by qPCR. Lachnospiraceae and its subordinate taxa were found to be the main differences in gut microbiota between responders and non-responders. The abundance of Lachnospira in responders was higher than that in non-responders. Lachnospira exhibits moderate diagnostic value in evaluating the efficacy of antihistamine. Lachnospira is a signature for predicting the efficacy of antihistamine in patients with CSU.

Topical VX-509 attenuates psoriatic inflammation through the STAT3/FABP5 pathway in keratinocytes.

BACKGROUND: Psoriasis is a chronic inflammatory disease, with lesions mainly manifesting as scaly erythematous plaques. The mild or moderate of psoriasis is the main type of patients in hospital, and topical application remains the preferred treatment option for psoriasis therapy, therefore, the development of novel topical agents has an essential role in psoriasis therapy. OBJECTIVE: To identify potential drugs for psoriasis topical treatment. METHODS: We performed drug screening by Imiquimod (IMQ)-induced psoriatic like inflammation in mouse model, followed mouse epidermis by RNA-seq to find the key molecules affecting the drug. The qRT-PCR, WB were performed to test mRNA and protein expression, and Chip assay had been conducted to examine Stat3 bound to promoter of FABP5. RESULTS: In this study, we identified VX-509, which topical application significantly attenuated IMQ-induced psoriatic like inflammation in mouse model. And then, we verified Epidermal Fatty acid binding protein (E-FABP/FABP5) was significantly decreased in VX-509 treated mouse epidermis by RNA-seq. FABP5 is a key molecule in lipid metabolism, administration of FABP5 inhibitor or knock down of FABP5 expression remarkably abrogated psoriatic inflammation as well as lipid metabolism. Mechanistically, our finding showed that VX-509 blocked IL-22 induced signaling pathway, particular in activation of Stat3. Furthermore, we identified Stat3 is a transcriptional factor associated with FABP5 promoters and VX-509 treatment remarkably attenuated IL-22-induced FABP5 expression through Stat3 in KCs. CONCLUSIONS: This study demonstrated administration of VX-509 is a potential promising topical drug for treatment of psoriasis, FABP5 is a critical targeted molecule in psoriasis therapy.

The length of stay and inpatient burden in inpatients with different psoriasis subtypes.

Background: Heavy disease burden of psoriasis has been indicated by previous studies. However, the cost of care and length of stay (LOS) in inpatients with different psoriasis subtypes were rarely addressed. This study aimed to investigate the cost of care and LOS in Chinese patients with different psoriasis types and to clarify the independent factors affecting LOS. Methods: We conducted a cross-sectional study by enrolling patients with psoriasis who were hospitalized between 13 Feb 2017 and 29 Mar 2021. Demographic and clinical characteristics of the patients were collected by reviewing their Electronic Medical Records. Multivariate linear regression was used to estimate the associations with adjustments. Results: A total of 310 adult patients with psoriasis were included (mean cost of care: 13.0±22.3 kCNY; mean LOS: 7.9±4.3 days). Statistically significant differences were found among patients with different psoriasis subtypes in LOS (P<0.001) but not in the cost of care (P=0.530). Relative to psoriasis vulgaris, pustular psoriasis (Adjusted coefficient: 2.37, 95% confidence interval (CI): 0.87-3.87) and erythrodermic psoriasis (Adjusted coefficient: 2.92, 95%CI: 1.38-4.47) were significantly associated with an increased LOS. Meanwhile, respiratory tract infections (Adjusted coefficient: 1.60, 95%CI: 0.11-3.10) also significantly increased the LOS. On the contrary, a decreased LOS was found in psoriatic arthritis patients treated with TNF-alpha inhibitors (Adjusted coefficient: -2.21, 95%CI: -4.37 to -0.05). Conclusions: LOS differed significantly among different psoriasis subtypes while the inpatient burden for a single hospitalization was alike. Infection is an important factor associated with a longer LOS. TNF-alpha inhibitors evidently reduced the total hospital stay period for patients with psoriatic arthritis.

Phototherapy for atopic dermatitis: Systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Phototherapies could represent an efficient option for the treatment of atopic dermatitis (AD), but the evidences available for clinical choices were contradictory. OBJECTIVE: This study aimed to evaluate the efficacy of different phototherapies on AD. METHODS: This systematic review and network meta-analysis included randomized controlled trials (RCTs) through searching keywords from PubMed, EMBASE, and the Cochrane library. We summarized different phototherapy types and scoring systems. Scoring Atopic Dermatitis (SCORAD) absolute score changes were estimated by mean differences (MDs) and standard deviations (SDs) and then included in the network meta-analysis. The effect sizes of comparison of different phototherapies were presented as MDs and 95% confidence intervals (CIs). Egger's test was used to evaluate publication bias. RESULTS: Eleven RCTs were included in the systematic review and 4 studies in the network meta-analysis. Based on the pooled estimates, medium-dose ultraviolet A1 (UVA1) cold light was superior to medium-dose UVA1 (MD 8.92; 95% CI: 5.60-12.24) but no significant difference between high-dose (UVA1) and medium-dose UVA1 cold light (MD 0.66; 95% CI: -5.57 to 6.90). Publication bias was not supported by Egger's test (P = .168). CONCLUSIONS: Due to possible long-term adverse effects of high-dose UVA1, medium-dose UVA1 cold light appears to be the superior form for AD.

Identification of gut microbiota signatures in symptomatic dermographism.

Symptomatic dermographism (SD) is a recurrent inflammatory skin disease related to immunity; however, the details remain elusive. In view of the important role of gut microbiota in immune regulation, the purpose of this study is to investigate the alterations of gut microbiota in SD and explore the potential bacterial biomarkers for diagnosis. A case-control study including SD patients and normal controls (NCs) was carried out. Gut microbiota of the participants was analysed by the 16S rDNA sequencing of faecal samples. The linear discriminant analysis effect size and the receiver operating characteristic curve (ROC) analysis were used to identify the bacterial biomarkers. Forty-four participants were included in this study. The alpha-diversity and beta-diversity of gut microbiota differed significantly between SD patients and NCs. The abundance of Verrucomicrobia, Ruminococcaceae and their subordinate taxa were reduced in SD patients, while Enterobacteriales and its subordinate taxon exhibited higher relative abundance compared with NCs. Subdoligranulum and Ruminococcus bromii showed a potential diagnostic value for SD, and Prevotella stercorea was negatively relevant to duration of SD. Furthermore, the pyruvate, butyric acid and histamine metabolism pathway were likely to be involved in the pathogenesis of SD. Our results revealed that the gut microbiota of SD patients experienced obvious changes, and Verrucomicrobia, Ruminococcaceae and Enterobacteriales were microbiota signatures for SD.

The Classification of Six Common Skin Diseases Based on Xiangya-Derm: Development of a Chinese Database for Artificial Intelligence.

BACKGROUND: Skin and subcutaneous disease is the fourth-leading cause of the nonfatal disease burden worldwide and constitutes one of the most common burdens in primary care. However, there is a severe lack of dermatologists, particularly in rural Chinese areas. Furthermore, although artificial intelligence (AI) tools can assist in diagnosing skin disorders from images, the database for the Chinese population is limited. OBJECTIVE: This study aims to establish a database for AI based on the Chinese population and presents an initial study on six common skin diseases. METHODS: Each image was captured with either a digital camera or a smartphone, verified by at least three experienced dermatologists and corresponding pathology information, and finally added to the Xiangya-Derm database. Based on this database, we conducted AI-assisted classification research on six common skin diseases and then proposed a network called Xy-SkinNet. Xy-SkinNet applies a two-step strategy to identify skin diseases. First, given an input image, we segmented the regions of the skin lesion. Second, we introduced an information fusion block to combine the output of all segmented regions. We compared the performance with 31 dermatologists of varied experiences. RESULTS: Xiangya-Derm, as a new database that consists of over 150,000 clinical images of 571 different skin diseases in the Chinese population, is the largest and most diverse dermatological data set of the Chinese population. The AI-based six-category classification achieved a top 3 accuracy of 84.77%, which exceeded the average accuracy of dermatologists (78.15%). CONCLUSIONS: Xiangya-Derm, the largest database for the Chinese population, was created. The classification of six common skin conditions was conducted based on Xiangya-Derm to lay a foundation for product research.

The role of Langerhans cells in epidermal homeostasis and pathogenesis of psoriasis.

The skin is the main barrier between the human body and the outside world, which not only plays the role of a physical barrier but also functions as the first line of defence of immunology. Langerhans cells (LCs), as dendritic cells (DC) that play an important role in the immune system, are mainly distributed in the epidermis. This review focuses on the role of these epidermal LCs in regulating skin threats (such as microorganisms, ultraviolet radiation and allergens), especially psoriasis. Since human and mouse skin DC subsets share common ontogenetic characteristics, we can further explore the role of LCs in psoriatic inflammation.