This paper studies the challenging issue of privacy-preserving formation control for second-order multi-agent systems under stochastic switching topologies, mainly protecting privacy of true initial formation errors. Considering the circumstances of communication noises among agents, distributed intermittent event-triggered privacy-preserving formation algorithms including the fuzzy logic system are given. Meanwhile, a novel privacy-preserving mask function is proposed, where indistinguishable space is increased by 26.2% than ones in existing literatures. Based on stochastic stability analysis and graph theory, sufficient conditions of mean square formation with the bound error are derived. Moreover, optimal controllers for the leader are proposed within the intermittent event-triggered privacy-preserving framework. In order to deal with nonlinear and unknown function, we exploit the idea of adaptive control to parameterize partial derivative of corresponding cost function, which is another different technique rather than the adaptive dynamic programming one. Finally, two simulation examples are given to indicate feasibility of our proposed theoretical results.

Hidradenitis suppurativa (HS), also known as acne inversa (AI), is a chronic, recurrent inflammatory disease of the pilosebaceous unit that primarily affects intertriginous areas and is characterized by recurrent, painful, deep-seated inflammatory lesions. The pathogenesis of HS/AI is multifactorial, involving genetic susceptibility, immune dysregulation, microbial imbalance, and obesity. HS/AI remains difficult to manage, and current treatment aims to reduce the frequency and duration of flares, decrease disease severity, and improve quality of life. Treatment selection should be guided by disease severity and activity. Pharmacologic therapies include antibiotics, biologics, small-molecule agents, retinoids, and immunosuppressants, while adjunctive approaches include surgical interventions and energy-based therapies. This updated consensus aims to standardize the diagnosis and management of HS/AI in China and to improve clinical practice by providing a stepwise, multidisciplinary treatment framework in which interventions are stratified according to disease severity and recommendation strength. Recommendation strength was determined by expert voting: an agreement rate of ≥85% indicated “Should be recommended,” ≥75% to <85% indicated “Could be recommended,” ≥50% to <75% indicated “May be considered,” and <50% indicated “No consensus reached.” Key recommendations reaching the ≥85% agreement threshold included severity-based treatment selection, topical clindamycin for mild localized disease, systemic tetracyclines for mild-to-moderate HS/AI, and biologics, including adalimumab, secukinumab, and bimekizumab, for moderate-to-severe disease. The consensus has been registered on the International Practice Guidelines Registry Platform (No: PREPARE-2025CN1964).

Metabolic reprogramming toward aerobic glycolysis is increasingly recognized as a key mechanism in the pathogenesis of psoriasis, but the underlying regulatory mechanisms remain unclear. Here, we identify Toll-interacting protein (TOLLIP) as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. We found that TOLLIP is significantly upregulated in psoriatic lesions, and its genetic deletion in mice exacerbated disease severity in imiquimod (IMQ)-induced psoriasis models. Mechanistically, TOLLIP interacts with the rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) via its coupling of ubiquitin to ER degradation (CUE) domain (179-274 aa), inhibits PKM2's metabolic enzyme activity and attenuates aerobic glycolysis, thereby mitigating keratinocyte hyperproliferation and inflammation. Therapeutic delivery of Tollip or Tollip (179-274 aa) via adeno-associated virus (AAV) vectors ameliorated psoriasis progression in mice. Our findings establish the TOLLIP-PKM2-glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target.

We aimed to explore the Modified Qingxin Decoction for Invigorating the Spleen (MQDIS) in the treatment of atopic dermatitis (AD) the efficacy and safety. We selected AD192 patients treated from June 2018 to June 2023 as a retrospective case-control study, and divided the patients into the observation group and the comparison group with 96 cases. Patients in the control group received conventional treatment. Observation group was treated with MQDIS on the basis of comparison group. Symptoms and signs, Scoring Atopic Dermatitis Index (SCORAD) score, itch score, dryness score and quality of life index were analyzed in the two groups. The improvement of skin area, severity, pruritus and sleep in the comparison group was better than that in the observation group, especially in the severity and sleep, and the statistical difference was very significant.(P-value<0.05).SCORAD score and itch degree of both groups decreased, the difference was statistically significant.(P-value<0.05).MQDIS for treating AD had a good effect on improving various points of skin lesion, dry points and quality of life, and the recurrence rate was lower, it was safe and effective.

Basal cell carcinoma (BCC) is one of the most common malignant skin tumors, predominantly occurring in sun-exposed areas such as the head and face. The combination of surgery and photodynamic therapy (PDT) enables rapid tumor clearance and comprehensive regional treatment of cancerous tissues, effectively reducing recurrence rates. This report presents two cases of patients with basal cell carcinoma in special facial areas treated with modified surgical excision combined with photodynamic therapy.

This study aimed to investigate the role of transforming growth factor-beta 3 (TGF-β3) secreted by adipose-derived stem cells (ADSCs) in suppressing melanin synthesis during the wound healing process, particularly in burn injuries, and to explore the underlying mechanisms involving the cAMP/PKA signaling pathway. ADSCs were isolated from C57BL/6 mice and characterized using flow cytometry and differentiation assays. A burn injury model was established in mice, followed by UVB irradiation to induce hyperpigmentation. Mice were divided into four groups: control (PBS), ADSCs, ADSCs with TGF-β3 overexpression, and ADSCs with TGF-β3 knockdown. Melanin deposition was assessed via Fontana Masson staining, while ELISA measured the expression of MC1R and α-MSH. Western blotting was used to examine TGF-β3 and the activation of cAMP/PKA signaling pathway. Mice treated with ADSCs overexpressing TGF-β3 showed significant reductions in melanin deposition and suppressed expression of MC1R and α-MSH compared to controls. Western blot results revealed that the cAMP/PKA signaling pathway was downregulated in the TGF-β3-overexpressing ADSC group. In contrast, the knockdown of TGF-β3 led to increased melanin deposition and higher cAMP/PKA pathway activity, correlating with greater expression of MC1R and α-MSH. TGF-β3 secreted by ADSCs effectively inhibits melanin synthesis during wound healing, with potential effects on the cAMP/PKA signaling pathway. These findings suggest that TGF-β3 could serve as a potential therapeutic target for managing post-burn hyperpigmentation.

BACKGROUND:D-2570, a TYK2 inhibitor, is currently being developed for autoimmune diseases including psoriasis and ulcerative colitis. OBJECTIVE:To evaluate the efficacy and safety of D-2570 in patients with moderate-to-severe plaque psoriasis. METHODS:In the randomized, double-blind, phase 2 study (NCT06278350), patients were randomized 1:1:1:1 to receive D-2570 at 18/27/36 mg, or placebo once daily for 12 weeks. The primary endpoint was the proportion of patients achieving psoriasis area severity index (PASI) 75 at week 12. Secondary endpoints included PASI 75/90/100 and static Physician Global Assessment (sPGA) score of 0/1, safety, and pharmacokinetic/pharmacodynamic characteristics. RESULTS:At week 12, significantly higher response rates for PASI 75 (85.0% to 90.0%, vs 12.5%, P < .001 for all), PASI 90 (70.7% to 77.5% vs 5.0%, P < .001), PASI 100 (39.0% to 50.0% vs 2.5%, P < .005) and sPGA 0/1 (80.5% to 87.5% vs 20.0%, P < .001) were achieved in patients receiving D-2570 at 18/27/36 mg versus placebo. D-2570 was well tolerated, and most treatment-emergent adverse events were mild/moderate. D-2570 exhibited favorable pharmacokinetic properties and effectively suppressed IL-17A levels in patients. LIMITATIONS:Small sample size, relatively short duration of treatment and follow-up. CONCLUSION:D-2570 demonstrated a high efficacy with favorable safety profile in patients with moderate-to-severe plaque psoriasis.

BACKGROUND:SYSA1902 is a biosimilar of ustekinumab. OBJECTIVE:Evaluate the efficacy and safety of SYSA1902 compared with reference ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS:Eligible patients were randomized to receive SYSA1902 or ustekinumab (Stelara, Janssen) 45 mg subcutaneously at week 0, 4, 16, 28, and 40. The primary end point was the percentage improvement from baseline in psoriasis area and severity index (PASI) at week 12. Equivalence was verified if the 95% CI of difference was within ± 15%. RESULTS:A Total of 446 patients were assigned to SYSA1902 (n = 224) and ustekinumab groups (n = 222). At week 12, the mean percentage change from baseline in PASI was 86.4% in the SYSA1902 group and 84.7% in the ustekinumab group, with a difference of 1.68% (95% CI, -1.45 to 4.81), which fell within the equivalence margins. PASI 75 at week 12 was achieved by 185 (83.3%) of patients receiving SYSA1902 versus 172 (79.3%) receiving ustekinumab. Overall treatment-emergent adverse events rate was 89.3% and 85.6% in the SYSA1902 and ustekinumab groups. Most treatment-emergent adverse events were mild to moderate, with upper respiratory tract infection being the most common. LIMITATIONS:Data limited to Chinese patients. CONCLUSION:SYSA1902 is equivalent to ustekinumab for the treatment of moderate-to-severe plaque psoriasis.

Plantar warts are a common clinical condition caused by human papillomavirus infection, and are more likely to occur in individuals with a history of trauma or weakened immune systems. Patients with a long history of the disease may experience pain while walking or standing, and the skin lesions may gradually increase in number and size. Clinical diagnosis is relatively straightforward, Common treatment methods include laser therapy, cryotherapy, surgical excision, and medication. However, high recurrence rates and significant trauma remain challenges in clinical treatment. In this case, the patient had a long history of the disease and had undergone stomach cancer surgery a year prior, with multiple treatments attempted without satisfactory results. We employed carbon dioxide laser therapy in combination with photodynamic therapy, which yielded good results, and there has been no recurrence after six months of follow-up treatment.

Background Lichen planus is a chronic inflammatory disease of the skin and mucosa. Due to its unknown etiology, many patients have poor treatment effect, which seriously affects the quality of life. It is necessary to further study the pathogenesis of lichen planus to provide a new target for drug screening. Objective To investigate the effects of metformin on keratinocyte proliferation and apoptosis through NLRP3 inflammasome pathway. Methods Experiment period: 2020 to 2023. In vitro experiment, human immortalized keratinocytes (HaCaT) were divided into 4 groups: control group, lipopolysaccharide group (LPS group: 5 μg/mL), metformin group (Met group: 10 mmol/L), LPS combined with metformin group (LPS+Met group: metformin was treated with 10 mmol/L after LPS 5 μg/mL stimulation for 2 hours). In vivo experiments, BALB/c mice were used as research objects to induce psoriatic dermatitis model by applying imiquimod on the back skin, and metformin cream was prepared for treatment. The mice were randomly divided into 3 groups: control group, imiquimod group (IMQ group), and imiquimod plus metformin group (IMQ+Met group). Each group has 10 mice. Mice in the control group were smeared with petroleum jelly on the back, mice in the IMQ group were smeared with imiquimod ointment on the back, mice in the IMQ+Met group were smeared with metformin cream after 12 h of IMQ ointment. Once a day for seven consecutive days. Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the effects of metformin on the proliferation and apoptosis of HaCaT cells. Western Blotting, enzyme-linked immunosorbent assay (ELISA) and Caspase-1 activity assay were used to detect the expression and activity of NOD-like receptor protein 3 (NLRP3) inflammasome pathway protein in HaCaT cells treated with metformin. Finally, hematoxylin-eosin (HE) staining and immunohistochemistry were used to detect the anti-inflammatory effect of metformin on imiquimod-induced psoriatic dermatitis in mice. Results The results of CCK-8 experiment showed that the 48 h survival rate of HaCaT cells in LPS, Met and LPS+Met groups were lower than that in control group, while the 48 h survival rate of HaCaT cells in LPS+Met group was higher than that in LPS group (P<0.05). Flow cytometry results indicated that the proportions of G2/M phase and apoptosis of HaCaT cells at 48 h in LPS and Met groups were higher than those in control group, while the proportion of G2/M phase and apoptosis of HaCaT cells at 48 h in LPS+Met group were lower than those in LPS group (P<0.05). Western Blotting results demonstrated that the expression of Caspase-1 p40, Caspase-1 p20, interleukin (IL) -1β and IL-18 proteins in NLRP3 inflammasome pathway of HaCaT cells in LPS and Met groups were higher than those in control group. The expression of Caspase-1 p40, Caspase-1 p20, IL-1β and IL-18 of HaCaT cells in LPS+Met group were lower than those in LPS group (P<0.05). ELISA results showed that the levels of IL-1β, IL-18 and relative activity of Caspase-1 in NLRP3 inflammasome pathway of HaCaT cells in LPS and Met groups were higher than those in control group. The levels of IL-1β, IL-18 and relative activity of Caspase-1 of HaCaT cells in LPS+Met group were lower than those in LPS group (P<0.05). Metformin application in IMQ+Met group significantly improved the imiquimod skin damage observed by HE staining. Immunohistochemical results reported that the expressions of NLRP3, Caspase-1, IL-1β and IL-18 were significantly decreased in IMQ+Met group. Conclusion Metformin bidirectional regulates the proliferation and apoptosis of skin keratinocytes through the NLRP3 inflammasome pathway, and can improve the skin damage induced by imiquimod in psoriasis mice, which is expected to provide a theoretical basis for the clinical use of metformin in the treatment of lichen planus.

Background Patients with syphilis are the only source of infection, which can be transmitted through sexual contact and mother-to-child and blood transmission, and rarely through contaminants. The clinical manifestations of syphilis are complex and variable, and can be easily misdiagnosed. This article reports a case of syphilis in a child with “psoriasis”-like lesions who was fed pre-chewed food. Case presentation An 18-month-old girl presented with mung bean to peanut-sized erythema and papules scattered on both lower limbs and perianal area; some of the erythema was covered with scales, with clear boundaries and no fusion. The case was misdiagnosed as “psoriasis” in the local hospital until the child and her mother tested positive for syphilis in the outpatient clinic of our hospital. The girl’s mother had a habit of chewing food in her mouth before feeding it to her child. Conclusions Consumption of food chewed by a person with syphilis can lead to infection, and attention should be paid to the possible ways and means of being infected.

This paper investigates circle formation control for the first-order multi-agent systems with privacy protection using a reinforcement-learning intermittent event-triggered method. Firstly, when the communication network suffers risks of information disclosure and denial-of-service (DoS) attack, an adaptive state observer is proposed to estimate the state of the multi-agent system. Moreover, based on the state estimation, a novel hybrid circle formation algorithm including the optimal controller is proposed as well as it can minimize the cost function. In light of stochastic analysis and Lyapunov stability theory, sufficient conditions for circle formation are derived. Furthermore, owing to the eavesdropping threat between the observer and the controller, an improved Paillier homomorphic encryption algorithm is employed to ensure data privacy, which requires less computation compared to some existing methods. Finally, simulation examples prove the accuracy of the theoretical results.

Giant basal cell carcinoma (GBCC) is a rare and clinically aggressive subtype of BCC. We report an unusual case of a 71-year-old male with a 30-year history of a slowly enlarging tumor on the extensor surface of his left upper arm. The lesion presented as a giant, irregular ulceration measuring 12×10 cm with coalescing verrucous borders. Histopathological examination confirmed the diagnosis, revealing characteristic nests of basaloid cells with peripheral palisading and stromal retraction artifact in the dermis. Immunohistochemical staining was positive for Ber-EP4, CK15, Ki-67, Bcl-2. The patient was diagnosed with GBCC with Ulcer. Staging workup with computed tomography (CT) of the left humerus and axillary lymph node ultrasonography showed no evidence of metastasis. The patient was successfully treated with slow Mohs micrographic surgery. Subsequent histopathological assessment of the excised specimen confirmed tumor-free margins. At 12-month follow-up, no local recurrence was observed. This case highlights the importance of recognizing GBCC in uncommon locations and demonstrates the efficacy of slow Mohs technique for achieving complete excision in large, complex tumors.

Melanoma is a highly heterogeneous and aggressive malignancy. Hypoxia within the tumor microenvironment is closely associated with tumor progression. However, the role of hypoxia-inducible factor 2α (HIF2α), a key transcription factor, in melanoma remains poorly understood. In this study, transcriptome analysis compared HIF2α expression between melanoma patient and control samples. Single-cell RNA sequencing categorized cells into high- and low-HIF2α expression groups. Ligand-receptor interactions (CellChat), enrichment analysis (GSEA/GSVA), immune regulatory network, and metabolic pathway analyses were performed. The correlation between HIF2α and genes involved in hypoxia, autophagy, and epithelial-mesenchymal transition (EMT) was explored, alongside its relationship with clinical stage. Experimentally, A375 cells were cultured under normoxic and hypoxic conditions, transfected with ShRNA-NC or ShRNA-HIF2α, and mRNA levels of HIF2α, E-cadherin, N-cadherin, and Vimentin were quantified using real-time PCR. Differential expression analysis showed significant upregulation of HIF2α in melanoma samples. Ligand-receptor interaction analysis emphasized its role in modulating the tumor microenvironment. Enrichment analyses (GSEA/GSVA) revealed HIF2α involvement in key oncogenic pathways. Correlation analysis linked HIF2α to genes related to hypoxia, autophagy, and EMT, and its expression was associated with advanced clinical stages. In vitro, hypoxia increased HIF-2α, N-cadherin, and Vimentin mRNA levels, while decreasing E-cadherin. HIF-2α knockdown reversed these effects, promoting E-cadherin and suppressing N-cadherin and Vimentin under hypoxia. This study underscores the critical role of HIF2α in melanoma progression, suggesting its involvement in regulating the tumor microenvironment and associated metabolic pathways. As a potential biomarker and therapeutic target, HIF2α offers new insights into the clinical management and treatment of melanoma.

In this paper, a fuzzy neural-network sliding mode control (FNNSMC) problem for nonlinear systems is investigated utilizing a fuzzy integral switching function (FISF). Different from the previous work on integral sliding mode control (ISMC), four terms are included in the designed FISF, which deeply merges the characteristics of the fuzzy membership functions (FMFs). The FMFs and state variables are used to design the first two terms of a FISF. An integral term on a derivative of the FMFs is considered to design the last term, which can reflect more features of fuzzy systems compared with the existing methods. Subsequently, combining with the designed FISF, a Gaussian radial basic neural network is used to devise a FNNSMC law, which can effectively mitigate the amplitude of the high-frequency chattering. Additionally, a fuzzy Lyapunov method and a switching idea are employed to analyze the asymptotical stability of the sliding motion, which can reduce the conservatism of the stability criteria. In the end, the availability and advantages of the proposed theoretical results can be verified via some simulations.

This paper investigates disturbance-resistant intermittent event-triggered optimal formation control problems of second-order multi-agent systems by using the reinforcement learning method, which takes into account the influence of network damage including denial-of-service (DoS) and deception attacks, stochastic noises, and unknown external disturbances. Firstly, we propose a novel disturbance observer based on adaptive control to estimate unknown external disturbances under an event-triggered mechanism. Secondly, by use of estimation of disturbances, an innovative intermittent event-triggered optimal formation algorithm is given. By applying theories such as Lyapunov stability and stochastic stability, sufficient conditions are derived to guarantee that all agents achieve the desired formation in mean square sense. Additionally, in the model-free case, the optimal controller is solved using the least squares method, which is computationally less complex than some existing approaches. Finally, the theoretical results are effectively validated through simulation examples.

Polo-like kinase 4 (PLK4) involves in tumor progression via regulating centriole duplication. This study aimed to investigate correlations of PLK4 with tumor characteristics and survival in cutaneous melanoma patients undergoing surgical resection. Tumor specimens of 43 patients were retrieved for PLK4 determination by immunohistochemistry (IHC). The IHC score was a multiplication of staining intensity and percentage of staining-positive cells. This study found the median and mean tumor PLK4 IHC score was 0.0 (interquartile range: 0.0-6.0) and 3.5 ± 3.2 (mean ± SD), respectively. Elevated tumor PLK4 IHC score correlated with lymph node metastasis (P = 0.028), higher tumor node metastasis (TNM) stage (P = 0.004), and adjuvant therapy (P =0.029). Tumor PLK4 IHC score > 0 did not relate to disease-free survival (DFS) or overall survival (OS) (both P > 0.050). Tumor PLK4 IHC score > 3 associated with decreased DFS (P = 0.027), but not OS (P = 0.098). Five-year DFS rate of patients with tumor PLK4 IHC score = 0 and > 0 was 75.0% and 53.9%, correspondingly; while the rate of patients with the score ≤ 3 and > 3 was 81.0% and 37.5%, respectively. Five-year OS rate of patients with the score = 0 and > 0 was 100.0% and 66.3%, accordingly; whereas the rate of patients with the score ≤ 3 and > 3 was 85.7% and 61.5%, correspondingly. According to forward-step multivariate analysis, neither the score > 0 nor > 3 independently related to worse DFS and OS (all P > 0.050). Further validation via THE HUMAN PROTEIN ATLAS database showed high PLK4 RNA expression associated with shortened OS in melanoma patients (P = 0.001). PLK4 correlates with lymph node metastasis, increased TNM stage, and poor DFS in cutaneous melanoma patients undergoing surgical resection.