Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

Enhancement of Facial Rejuvenation Through a Combination of 1565 nm Non-Ablative Fractional Laser with 30% Supramolecular Salicylic Acid.

The 1565 nm non-ablative fractional laser can effectively stimulate collagen regeneration, achieving the effect of skin rejuvenation and anti-aging. In recent years, it has been widely used in dermatology, especially in facial rejuvenation, treatment of stretch marks, and acne scar treatment, with significant results. However, after the 1565 nm non-ablative fractional laser treatment, patients may experience short-term erythema and edema. The inflammation after treatment may also cause pigmentation, making it difficult for some patients to accept. This article introduces a treatment method of 1565 nm non-ablative fractional laser combined with 30% super molecular salicylic acid for facial rejuvenation, effectively reducing posttreatment erythema and post-inflammatory pigmentation. The method includes specific treatment steps and the respective endpoint reactions of each step. The method starts by selecting appropriate energy parameters for the 1565 nm non-ablative fractional laser treatment, followed immediately by the application of 30% supramolecular salicylic acid. The treatment should be stopped when a frosty reaction occurs. The purpose of this project is to provide patients with a safer new method of facial rejuvenation treatment.

HDAC1-mediated regulation of KDM1A in pemphigus vulgaris: unlocking mechanisms on ERK pathway activation and cohesion loss.

Pemphigus vulgaris (PV) is an autoimmune skin disorder characterized by the loss of cell cohesion, with the histone deacetylase 1 (HDAC1) and lysine demethylase 1A (KDM1A) playing critical roles in its pathogenesis. This study aimed to elucidate the molecular mechanisms behind PV, focusing on the function of HDAC1 and KDM1A in disease onset and progression. Based on in vitro and in vivo PV models, we observed a significant increase in HDAC1 mRNA and protein levels in skin tissues of PV patients. Inhibition of HDAC1 ameliorated cell damage and reduced the loss of cell cohesion in human epidermal keratinocytes (HEKs) induced by PV-IgG. Our findings suggest that HDAC1 regulates KDM1A expression through deacetylation, with a notable deficiency in KDM1A expression in PV. Overexpression of KDM1A mitigated cell damage and cohesion loss. The extracellular signal-regulated kinase (ERK) pathway serves as a downstream executor of the HDAC1/KDM1A axis. Inhibiting HDAC1 and increasing KDM1A expression suppressed ERK phosphorylation, reducing PV-related apoptosis. These insights provide a new perspective on treating PV, highlighting the therapeutic potential of targeting HDAC1 expression. The regulatory mechanism of the HDAC1/KDM1A/ERK axis offers crucial clues for understanding PV pathogenesis and developing novel treatments.

Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: A randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Vunakizumab, a novel anti-interleukin-17A antibody, has shown promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial. OBJECTIVE: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population. METHODS: Six hundred ninety subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4, and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16, and every 4 weeks thereafter). The co-primary endpoints were ≥90% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12. RESULTS: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%), and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P < .0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects. LIMITATIONS: Chinese subjects only; no active comparator. CONCLUSION: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis.

An observational and genetic investigation into the association between psoriasis and risk of malignancy.

The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin's lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis.

In Situ Pipe Prover Volume Measurement Method.

To improve the accuracy of in situ measurement of the standard volumes of pipe provers and to shorten the traceability chain, a new method of in situ pipe prover volume measurement was developed alongside a supporting measurement device. This method is based on the geometric dimension approach, which measures the inner diameter and length of a pipe prover to calculate its volume. For inner diameter measurement, a three-probe inner-diameter algorithm model was established. This model was calibrated using a standard ring gauge of Φ313 mm, with the parameters calculated through fitting. Another standard ring gauge of Φ320 mm was used to verify the inner diameters determined by the algorithmic model. A laser interferometer was employed for the segmented measurement of the pipe prover length. The comprehensive measurement system was then used for in situ measurement of the standard pipe prover. The newly developed system achieved an expanded uncertainty of 0.012% (k = 2) in volume measurement, with the deviation between the measured and nominal pipe prover volumes being merely 0.007%. These results demonstrate that the proposed in situ measurement method offers ultra-high-precision measurement capabilities.

Study on the dry shrinkage characteristics and size effect of swell-shrink characteristic soil.

Swell-shrink characteristic soils exhibit a high susceptibility to cracking during the drying process, which poses a significant risk of various geological disasters. Among these, the occurrence of drying shrinkage acts as a prerequisite for the cracking phenomenon. Therefore, it is of utmost importance to comprehend the specific characteristics associated with the drying shrinkage mechanism. To investigate the drying shrinkage behavior of swell-shrink characteristic soils, a series of drying shrinkage experiments were conducted on long strip samples of red clay and expansive soil. Utilizing three-dimensional digital image correlation (DIC) technology, the surface displacement, strain, and anisotropic shrinkage rates of the soil samples during the drying process were obtained, and the size effect on the drying shrinkage of swell-shrink characteristic soil were analyzed. The research findings are as follows: The displacement development of the soil samples in the X and Y directions can be divided into two stages: a linear growth stage and a stable displacement stage. In the Z direction, the soil surface deformation can be divided into three stages: soil surface arching, vertical shrinkage, and shrinkage stabilization. The drying shrinkage of swell-shrink characteristic soil exhibits anisotropy, with the vertical shrinkage rate being the largest, followed by the longitudinal and then the transverse directions. Additionally, the soil sample shrinkage exhibits a size effect, whereby the shrinkage rates in all directions increase with increasing sample width and thickness. During the drying shrinkage process, the stress state on the soil surface evolves from initial tensile strain to subsequent compressive strain. The strain at different positions and times within the soil sample is not uniform, resulting in the non-uniformity and anisotropy of the sample shrinkage. This study provides important insights into the cracking mechanism of swell-shrink characteristic soils and serves as a valuable reference for related laboratory experiments, which will contribute to better prediction and control the geological hazards caused by the drying shrinkage of swell-shrink characteristic soils.

Neutrophil extracellular traps promote macrophage inflammation in psoriasis.

Psoriasis is a chronic inflammatory skin disease connected with immune dysregulation. Macrophages are key inflammatory cells in psoriasis but the specific mechanism of their activation is not fully understood. Neutrophil extracellular traps (NETs) have been shown to regulate macrophage function. Here, we found that NET deposition was increased in psoriasis lesions. Peptidylarginine deaminase 4 (PAD4, a key enzyme for NET formation) deficiency attenuated skin lesions and inflammation in an imiquimod-induced psoriatic mouse model. Furthermore, the STING signaling pathway was markedly activated in psoriasis and abolished by PAD4 deficiency. PAD4-deficient mice treated with the STING agonist DMXAA exhibited more severe symptoms and inflammation than control mice. Mechanistically, the STING inhibitor C-176 inhibited NET-induced macrophage inflammation and further inhibited the proliferation of HaCaT cells. Our findings suggest an important role of NETs in the pathogenesis of psoriasis, and activation of macrophage STING/NF-κB signaling pathway might involve in NETs related psoriasis.

Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China.

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 <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685-11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068-2.343), traditional systemic (adjusted OR = 1.887, 95% CI = 1.263-2.818), and nonsystemic treatment (adjusted OR = 1.602, 95% CI = 1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. CONCLUSIONS: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT05961605).

Successful guselkumab treatment of a refractory psoriasis patient with Graves' disease: a case report.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

Increase in the incidence of invasive fungal infections due to Volvariella Volvacea.

PURPOSE: We aimed to show the increasing incidence of invasive fungal infections due to Volvariella Volvacea in patients with immunosuppression. METHODS: We present a case of an invasive fungal infection caused by Volvariella volvacea, and summarize the clinical and pathological features based on this case and a review of the literature. RESULTS: A total of seven patients with IFIs due to Volvariella Volvacea have been reported in the literature. The majority of cases have been obtained between 2019 and 2022. Including our case, they all had acquired immunosuppression. The lung and brain were the most commonly affected organs. All eight of these patients received antifungal therapy, but five still died one to seven months after occurrences of IFIs. CONCLUSION: The incidence of invasive fungal infections due to Volvariella Volvacea is increasing in recent years. It mainly occurred in patients with immunosuppression, especially in patients with malignant hematological cancers, and increased mortality.

Prevalence, outcomes and associated factors of SARS-CoV-2 infection in psoriasis patients of Southwest China: a cross-sectional survey.

In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine's effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Rapamycin protects mouse skin from ultraviolet B-induced photodamage by modulating Hspb2-mediated autophagy and apoptosis.

BACKGROUND: Continuous exposure to UVB is the main extrinsic cause of skin photodamage, which is associated with oxidative stress, DNA damage, apoptosis and degradation of collagen. Rapamycin, a mechanistic target inhibitor of rapamycin complex 1 (mTORC1), has been shown to play a crucial role anti-tumor and aging retardation, but its mechanism of action in UVB-induced photodamage still remains unknown. In this study, we investigated the role of rapamycin and Hspb2 (also known as Hsp27) in UVB-induced photodamage in mice. METHODS AND RESULTS: We constructed skin acute photodamage models on the ears of WT and Hspb2 KO mice, respectively, and administered rapamycin treatment. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels, with a significant increase in p53 levels and Bax/Bcl-2 ratio, a reduction in LC3II/I ratio and an increase in p62 levels in the KO mice compared to those in WT mice after the same dose of UVB irradiation. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. CONCLUSIONS: Rapamycin can alleviate skin photodamage from Hspb2 knockout to some extent. It may be a potential therapeutic drug for skin photodamage. In this study, we investigated the role of rapamycin and Hspb2 in UVB-induced photodamage in mice. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. We conclude that rapamycin and Hspb2 exert a synergistic protective effect in skin photodamage.

Tumor necrosis factor-α inhibitor for successful treatment of toxic epidermal necrolysis with severe infection: a case series.

Toxic epidermal necrolysis (TEN) is a rare severe cutaneous adverse reaction that involves more than 30% of the body surface area. TEN can be accompanied by a series of systemic symptoms and has a high risk of death. Tumor necrosis factor (TNF)-α inhibitors such as adalimumab and etanercept have been shown to be safe and effective for the treatment of TEN in some cases. However, clinical data on the use of TNF-α inhibitors to treat TEN with severe systemic infection are scarce. In the present study, three adult patients who developed TEN with serious active infection were successfully treated with etanercept. One of the three patients had active open pulmonary tuberculosis, and the other two had septicemia and/or fungal sepsis. All patients' skin lesions significantly improved after several days, and none of the patients developed emerging or re-emerging infectious diseases, adverse reactions, or a similar rash during follow-up. TNF-α inhibitors may be an effective treatment choice for TEN with severe systemic infection. However, further studies with large samples are still required for validation because clinical experience is limited.

Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS: We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS: Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS: Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

A Case Report of Adalimumab Successfully Treated a Severe Plaque Psoriasis Patient with Psoriatic End-Stage Renal Disease.

Psoriasis is a common chronic inflammatory skin disease that manifests itself not only on the skin but also on various tissues and organs of the body. While some psoriasis co-morbidities have been investigated, little is known about its association with impairment of renal function. In 2005, the concept of psoriatic nephropathy was first introduced by Indian nephrologists, suggesting a potential relationship between psoriasis and kidney disease. Adalimumab, a fully human recombinant immunoglobulin G1 monoclonal antibody against tumor necrosis factor (TNF)-α, has been shown to be a safe and effective treatment for patients with moderate to severe psoriasis. Here, we present a case of severe plaque psoriasis accompanied with end-stage renal disease (ESRD) treated with adalimumab. Following the case presentation is a discussion of the relationship between psoriasis and chronic kidney disease (CKD) / ESRD and the possible role of biologics in psoriasis-related kidney damage. The aim of this report is to increase dermatologists' awareness of psoriatic nephropathy as a complication of psoriasis and to raise awareness of the use of biologics in psoriasis.

Immunogenicity and protective efficacy of human metapneumovirus virus-like particles produced by a recombinant baculovirus in mice.

BACKGROUND: Human metapneumovirus (HMPV) causes respiratory tract infections among infant, elderly, and immunocompromised patients, with significant mortality. Currently no licensed vaccines or therapeutic agents of HMPV exist. METHODS: HMPV virus-like particle (VLP) was constructed by co-expressing fusion protein of HMPV and matrix 1 protein of influenza virus using the baculovirus expression. Mice were immunized with VLP with or without aluminum hydroxide (alum) adjuvant by intramuscular route respectively. Sera were determined for titers of IgG and neutralizing antibody. Splenic lymphocytes were determined by IFN-γ and IL-4 ELISPOT. Mice were challenged with HMPV, and protective efficacy was evaluated. RESULTS: We generated HMPV VLP in baculovirus expression system. After three times immunization, IgG antibody titers induced by VLP formulated with or without alum adjuvant group were 273,066 ± 100,331 and 136,533 ± 47,269 respectively, there was no difference (p Ëƒ 0.05); the neutralizing antibody titers vaccinated with VLP plus with alum adjuvant (266 ± 92) were higher than those of the VLP alone group (106 ± 37). For IFN-γ, mice vaccinated with VLP with or without alum adjuvant are 151 ± 36.4 and 77.0 ± 17.1SFC/106 respectively, there was difference (p = 0.03); For IL-4, they are 261.3 ± 38.7 versus 125.67 ± 29.78SFC/106 respectively, the difference was significant (p = 0.009). After challenge, in pathological analysis, the overall lesion scores in the VLP plus with and without alum adjuvant were 3.25 and 5.6 respectively, those of control group is 8. For immunohistochemical analyses, the average optical density of the lungs in the VLP immunized group containing adjuvant (9.07 ± 1.74) was lower than that in the VLP group without adjuvant (12.83 ± 2.31, p = 0.14). CONCLUSIONS: This is the first study to demonstrate that HMPV VLP was successfully prepared in the baculovirus expression system. HMPV VLP could induce specific humoral and cellular immune responses as well as protective efficacy, and aluminum hydroxide may be an effective adjuvant in mice.