Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy.

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.

Influence of Port-wine Stains on Quality of Life of Children and Their Parents.

Port-wine stains are congenital vascular malformations that affect the quality of life of children and their parents. This study used the Family Dermatology Life Quality Index and Children's Dermatology Life Quality Index to examine the effects of port-wine stains on the quality of life of children and their parents, including an in-depth, systematic analysis of the moderating effects of the children's sex and port-wine stain classification. The study included 43 children (25 girls and 18 boys) and their parents. The presence of a port-wine stain had a significantly greater impact on the quality of life of mothers than on that of fathers (p < 0.001). Port-wine stains in girls had a greater effect on paternal quality of life than did port-wine stains in boys (girls p < 0.01; boys p = 0.542). Severe types of port-wine stains exerted a greater impact on maternal quality of life (pink-red type, dark-red type, and purple-dark type: p < 0.001, p = 0.948 and p = 0.086, respectively). There-fore, clinicians should consider familial relationships and differences when offering psychological support.

Efficacy of Dupilumab in Children 6 Months to 11 Years Old With Atopic Dermatitis: A Retrospective Real-World Study in China.

Background: Atopic dermatitis (AD) is a common skin disease that affects patients' quality of life, especially in the pediatric population. Dupilumab has shown good efficacy and safety in the treatment of AD in adolescents and adults, but the real data on younger children using dupilumab are scarce. Objectives: We investigated the doses, efficacy, and safety of dupilumab in children with moderate-to-severe AD aged ≥6 months to 11 years. Methods: This single-center retrospective cohort analysis included dupilumab-treated patients with severe AD under 12 years of age. Primary endpoints included the proportion of Validated Investigator Global Assessment (vIGA) 0/1 achieved and the percentage change from baseline in eczema area and severity index (EASI) and SCORing Atopic Dermatitis (SCORAD) at week 24 (W24). Secondary endpoints were mean change in pruritus numerical rating score (P-NRS) and body surface area (BSA) after W24 of treatment, description of adverse events, and Children's Dermatology Life Quality Index (CDLQI) improvement from baseline in endpoints. Results: Fifty-seven patients were included (mean age 7.2 ± 3.0 years). The primary endpoint (vIGA = 0/1) was achieved by 51 of 57 (89.5%) patients at W24. Significant improvements in EASI, SCORAD, P-NRS, and CDLQI scores were observed from baseline to W24 with dupilumab treatment and remained until W40. In different age groups, the endpoint vIGA achieved 0/1: 95.2% (20/21) of younger children and 88.9% (32/36) of older children. No serious adverse drug reactions were reported. Conclusions: This study aimed to describe the safety and efficacy of dupilumab in pediatric patients and examined differences of efficacy with various doses. The outcomes are comparable with those of existing clinical trials. Phase III Clinical Trial: NCT03346434.

Indocyanine green based photodynamic therapy for keloids: Fundamental investigation and clinical improvement.

BACKGROUND: Keloid, a prevalent pathological skin lesion, presents significant challenges in terms of treatment efficacy. Photodynamic therapy (PDT), an increasingly popular adjuvant treatment, has shown significant potential in the management of various disorders, including cancer. However, the therapeutic potential of indocyanine green-mediated photodynamic therapy (ICG-PDT) for keloids has not yet been demonstrated. METHODS: In this study, we divided the experimental groups into control group, Photothermal Therapy group, Photodynamic Therapy group, and Combined Therapy group. The in vitro investigation aimed to optimize the clinical application of PDT for keloid treatment by elucidating its underlying mechanism. Subsequently, on this basis, we endeavored to manage a clinical case of keloid by employing surgical intervention in conjunction with modified ICG-PDT. RESULTS: Our investigation revealed an unexpected outcome that ICG-PDT maximally inhibited the cellular activity and migration of keloid fibroblasts only when photodynamic mechanism took effect. Additionally, the induction of autophagy and apoptosis, as well as the inhibition of collagen synthesis, were particularly evident in this experimental group. Furthermore, the above therapeutic effect could be achieved at remarkably low drug concentrations. Building upon the aforementioned experimental findings, we successfully optimized the treatment modality for the latest case and obtained a more favorable treatment outcome. CONCLUSIONS: This study investigated the mechanism of ICG-PDT treatment and optimized the in vivo treatment regimen, demonstrating the significant therapeutic potential of ICG-PDT treatment in clinical keloid treatment.

Efficacy, Safety, and Early Relapse After Cessation of Upadacitinib Versus Dupilumab in Adolescents with Moderate-to-Severe Atopic Dermatitis: A Real-World Study in China.

Background: The efficacy and safety of upadacitinib and dupilumab for atopic dermatitis (AD) in adolescent patients have been proven in clinical trials. However, few daily practice studies comparing agents have been conducted in this patient population. Objectives: This single-center retrospective cohort study aimed to investigate the efficacy, safety, and early relapse after cessation of upadacitinib and dupilumab for moderate-to-severe AD in Chinese adolescents. Methods: A retrospective study collected data on a cohort of 83 adolescent patients receiving upadacitinib or dupilumab from October 2021 to October 2023. This study comprised two main emphases. The first main emphasis involved the treatment phase, where the efficacy and safety of the two treatments were evaluated. Primary endpoints included the proportion of patients achieving an improvement of ≥50%, ≥75%, and ≥90% in Eczema Area and Severity Index (EASI) from baseline (EASI-50, EASI-75, EASI-90) and the proportion of patients achieving Validated Investigator Global Assessment (vIGA) 0/1 at week 4 and week 40. In the second main emphasis, AD recurrence after treatment discontinuation was assessed in the two treatment groups. The median time to relapse was calculated. Results: A total of 83 patients were enrolled. At week 4, the proportion of patients achieving the primary endpoints, including EASI-75 and EASI-90, was substantially higher with upadacitinib than with dupilumab (51.5% vs 14.0% [P < 0.001], 18.2% vs 2.0% [P < 0.05]). However, at week 40, higher proportion of patients on dupilumab were reaching EASI-50 and EASI-75 and vIGA 0/1. After the discontinuation of dupilumab or upadacitinib therapy, the Kaplan-Meier survival curve showed that the median time to relapse was 270 days in the dupilumab group and 18 days in the upadacitinib group. Conclusions: This study demonstrated that upadacitinib has superior short-term efficacy over dupilumab in adolescents with moderate-to-severe AD, whereas dupilumab trends toward better long-term remission over upadacitinib under the condition of treatment discontinuation in some patients.

Successful treatment of periungual warts with local hyperthermia: report of two cases.

Periungual warts are common warts that grow on the periungual or nail margin, and it's challenging to remove them due to their particular location, causing its high recurrence rate and brings difficulties to the treatments. We successfully cured two cases of stubborn periungual warts by local hyperthermia. A male with warts on his hands and knees and a girl with periungual warts on her fingers received local hyperthermia of 44 °C for 30 min a time. One month after the last treatment, their lesions disappeared entirely and did not relapse during the follow-up period. These two cases showed that local hyperthermia might be a safe and effective method for treating periungual warts in patients with poor traditional treatment.

Clinical and dermoscopic features of extramammary Paget's disease: A retrospective analysis of 49 cases.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that can be easily confused with other diseases due to its diverse clinical manifestations, delaying the timing of treatment. Therefore, early diagnosis is extremely important. It has been reported that dermoscopy can be used to evaluate superficial skin tumors. OBJECTIVE: To investigate the dermoscopic characteristics of EMPD diagnosed by histopathology and to develop a decision tree model that can provide clinicians with a reference to facilitate early diagnosis. METHODS: All patients were evaluated by dermoscopic and histopathologic examinations. Dermoscopic images were assessed, and a decision tree model was constructed using SPSS (version 25.0). RESULTS: A total of 49 patients were included in this study. We found that EMPD was most likely to be misdiagnosed when the disease duration was less than 2.5 years. Porcelain-white patches were the only key clinical feature other varying dermoscopic features could not be differentiated from those of EMPD-mimicking diseases. Polymorphic vessels were considered to be significant when the duration of the disease ranged from 0.1 year to 2.5 years. However, when the duration was >2.5 years, present (or absent) glomerular vessels were all considered EMPD. CONCLUSIONS: Dermoscopy can be used as an auxiliary diagnostic tool for the diagnosis and management of EMPD. The decision tree can guide clinical diagnosis further validation studies are necessary due to the limited number of cases.

Curcumol may alleviate psoriasis-like inflammation by inhibiting keratinocyte proliferation and inflammatory gene expression via JAK1/STAT3 signaling.

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation and differentiation of keratinocytes. Since curcumol exhibits anti-inflammatory properties in various diseases, we investigated its anti-inflammatory potential in stimulated human keratinocytes. Our data show that curcumol significantly inhibits proliferation and induces cell cycle arrest in NHEK cells stimulated with proinflammatory cytokines (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α; mix M5). In addition, curcumol markedly ameliorates inflammatory response and promotes differentiation of M5-stimulated NHEK cells. Curcumol inhibits activity of JAK1, resulting in the inhibition of STAT3, downregulation of cyclin D2, and cell cycle arrest in stimulated NHEK cells. Together, our data show that curcumol reduces proliferation and inflammatory gene expression in stimulated keratinocytes by inhibiting the JAK1/STAT3 signaling, suggesting that it might serve as a potential therapeutic option for the treatment of psoriasis.

The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma.

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT2 and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA3 and GEO4 databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM5 B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

The melanogenic effects and underlying mechanism of paeoniflorin in human melanocytes and vitiligo mice.

Vitiligo is a common depigmentary disease characterized as diagnosis simplicity and cure difficulty in view of the ambiguity of etiology, thus novel and effective treatments are urgently needed. Paeoniflorin, the major active compound extracted from the root of Paeonia lactiflora Pall, a traditional Chinese medicine, has been validated pharmacological properties such as antioxidant stress, a theory participating in the occurrence of vitiligo, but the effect on melanogenesis is still unclear. In this study, melanosythesis effect of paeoniflorin and the potential mechanism were evaluated. We found that treatment with paeoniflorin at the concentration of 10 µg/ml significantly increased melanin content and intracellular tyrosinase activity of human melanocytes, in accordance with the elevation of protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1). In addition, we also investigated that paeoniflorin promoted phosphorylation of cAMP-response element binding (CREB) and extracellular signal-regulated kinase (ERK) without affecting p38 and c-Jun N-terminal kinase (JNK). These results demonstrated that paeoniflorin had a synergistic effect on normal human melanocytes via ERK/CREB pathway with up-regulation of MITF and TRP-1, enhancing melanin synthesis. Meanwhile, the milder pathological changes in vitiligo mice treat with paeoniflorin also confirmed its potential in treating vitiligo. To sum up, we suggest that paeoniflorin may be a potential medicine of vitiligo treatment in clinical.