Evaluation of Confocal Laser Scanning Microscopy in Histological Classification and Photodynamic Therapy of Low-risk Basal Cell Carcinoma.

BACKGROUND: Confocal laser scanning microscopy (CLSM) is noninvasive technique utilized for identification and analysis skin malignancies. Several studies have applied CLSM in monitoring the therapeutic effects of basal cell carcinoma (BCC). OBJECTIVE: To investigate the diagnostic value of CLSM in low-risk BCC and the evaluation of photodynamic therapy (PDT). METHODS: We have diagnosed 149 patients with BCC using CLSM and histopathological examination. Based on histopathology, we summarized the classification information of low-risk BCC along with imaging features observed through CLSM. Thirty-four low-risk BCC patients underwent PDT treatment, and we used CLSM to evaluate its efficacy. RESULTS: Out of 149 participants were diagnosed with BCC by CLSM, 52 were pigmented type, 87 were nodular type and 10 were superficial type. After histopathological examination, 44 out of 52 were pigmented type, five were nodular type and three were superficial type. The results of CLSM were consistent with those of 87 nodular type and 10 superficial type. The CLSM features of nodular were observed in the tissue fissures around the tumor, the pigment mass was the CLSM characteristic of pigmented type. The simultaneous occurrence of inflammation and increased vasculature were characteristics of superficial. The effective rate of PDT was 100%, and the cure rate was 67.6%. At 12 months follow up, the recurrence rate of PDT was 11.8%, 15.0% for nodule type, 10.0% for pigmented type and 0% for superficial type. CONCLUSION: The tissue classification of CLSM for low-risk BCC was consistent with histopathology. CLSM can be used to monitor the efficacy of PDT for low-risk BCC.

The therapeutic effect of sufficient oxygen-rich PRP injection in facial rejuvenation by multiple objective evaluations in 26 cases.

Background: Ozone can enhance the expression of some growth factors (GFs) in platelet rich plasma (PRP), recent study showed oxygen-rich PRP (ozonized PRP) have better therapeutic effects on bone and joint diseases. PRP injection has been widely used in the treatment of facial rejuvenation, but the efficacy of sufficient oxygen-rich PRP in facial rejuvenation has not been studied. Objective: Firstly, we examined whether ozone treatment can increase the concentration of GFs of PRP in vitro. And then a variety of subjective and objective detection methods were used to evaluate the effect of sufficient(10-12 mL each time for the injection of face and neck) oxygen-rich (ozonized PRP) PRP injection in facial rejuvenation by follow-up for 6 months. At last, we investigated the satisfaction, side effects and pain score of the treatment through a questionnaire survey. Methods: The concentration of main GFs in PRP treated with different dose of ozone in vitro was measured by ELISA. Clinical picture, the collagen thickness of dermis by reflectance confocal microscope(RCM), skin conditions (including spots, ultraviolet (UV) spots, brown spots, red area, pores, wrinkles, texture and porphyrin) by VISIA were collected before treatment and each month follow-up visit after treatment until 6-month follow-up period was finished. Patients' satisfaction, side effects and pain score were collected at the end of follow-up period. Results: PRP treated by high-dose ozone (57 µg/mL, ozone/PRP volume ratio:1/1) in vitro showed a significant increase in endothelial growth factor (EGF) and transforming growth factor-ß (TGF-ß) compared to baseline(P < 0.05). Collagen thickness of forehead, cheek and neck improved significantly compare to the baseline until to the 6 months after treatment. Spots, UV spots, brown spots, red area and texture improved significantly compare to the baseline(P < 0.05). All of participants reported improvement and have a median pain score of 4.19. No serious adverse events were observed. Conclusions: Ozone treatment can increase the concentration of GFs such as EGF and TGF-ß in PRP in vitro. Sufficient oxygen-rich PRP injection may be an effective and promising method to treat facial rejuvenation.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Circadian rhythm of cutaneous pruritus. / 皮肤瘙痒的昼夜节律.

One of the most common and significant symptoms for skin disorders is pruritus. Additionally, it serves as a significant catalyst for the exacerbation or reoccurrence of skin diseases. Pruritus seriously affects patients' physical and mental health, and even the quality of life. It brings a heavy burden to the patients, the families, even the whole society. The pathogenesis and regulation mechanisms for pruritus are complicated and have not yet been elucidated. Previous clinical studies have shown that itch worsens at night in scabies, chronic pruritus, atopic dermatitis, and psoriasis, suggesting that skin pruritus may change with circadian rhythm. Cortisol, melatonin, core temperature, cytokines, and prostaglandins are the main regulatory factors of the circadian rhythm of pruritus. Recent studies have shown that some CLOCK genes, such as BMAL1, CLOCK, PER, and CRY, play an important role in the regulation of the circadian rhythm of pruritus by regulating the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor kappa-B (NF-κB) signaling pathways. However, the mechanisms for circadian clock genes in regulation of circadian rhythm of pruritus have not been fully elucidated. Further studies on the mechanism of circadian clock genes in the regulation of circadian rhythm of pruritus will lay a foundation for elucidating the regulatory mechanisms for pruritus, and also provide new ideas for the control of pruritus and the alleviation of skin diseases.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

The role of NLRP3 inflammasome in type 2 inflammation related diseases.

Type 2 inflammation related diseases, such as atopic dermatitis, asthma, and allergic rhinitis, are diverse and affect multiple systems in the human body. It is common for individuals to have multiple co-existing type 2 inflammation related diseases, which can impose a significant financial and living burden on patients. However, the exact pathogenesis of these diseases is still unclear. The NLRP3 inflammasome is a protein complex composed of the NLRP3 protein, ASC, and Caspase-1, and is activated through various mechanisms, including the NF-κB pathway, ion channels, and lysosomal damage. The NLRP3 inflammasome plays a role in the immune response to pathogens and cellular damage. Recent studies have indicated a strong correlation between the abnormal activation of NLRP3 inflammasome and the onset of type 2 inflammation. Additionally, it has been demonstrated that suppressing NLRP3 expression effectively diminishes the inflammatory response, highlighting its promising therapeutic applications. Therefore, this article reviews the role of NLRP3 inflammasome in the development and therapy of multiple type 2 inflammation related diseases.

A Phase-III Noninferiority, Randomized Controlled Trial of Letibotulinum Toxin A for the Improvement of Moderate-to-Severe Glabellar Wrinkles in China.

Background: Letibotulinum toxin A has an established efficacy and safety profile for aesthetic treatment of glabellar wrinkles. This study was conducted to demonstrate the noninferiority of letibotulinum toxin A versus onabotulinum toxin A in improving the appearance of moderate-to-severe glabellar wrinkles in Chinese patients. Methods: This phase-III multicenter, randomized, parallel positive control, double-blinded study compared the efficacy and safety of letibotulinum toxin A and onabotulinum toxin A. Eligible participants were randomized 3:1 to receive 20 U of letibotulinum toxin A or onabotulinum toxin A and were observed for 16 weeks postinjection. The primary endpoint was noninferiority in the proportion of study participants receiving a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an institution evaluator at maximum frown at week 4. Secondary endpoints included assessments at rest, photographic assessment of efficacy, and subjective self-assessment of the study participants. Results: The proportion of participants (N = 500) receiving a score of 0 or 1 at maximum frown by the institution evaluator at week 4 was 88.49% for letibotulinum toxin A and 87.39% for onabotulinum toxin A (difference, 1.10%; 95% confidence interval, -5.02 to 8.82; P = 0.7469). No significant differences were observed between the treatments for secondary efficacy or safety endpoints. Participants' self-assessment and satisfaction tended to be higher for letibotulinum toxin A than onabotulinum toxin A. Conclusion: Letibotulinum toxin A is noninferior to onabotulinum toxin A in improving the appearance of moderate-to-severe glabellar wrinkles in Chinese patients.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

WTAP-Mediated N6-Methyladenosine of RNAs Facilitate the Pathophysiology of Atopic Dermatitis.

N6-methyladenosine (m6A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m6A-mRNA epitranscriptomic microarray to screen for differentially expressed genes and their m6A levels and m6A-related enzymes in patients with AD. We confirmed that the m6A RNA methyltransferase WTAP and 2 candidate differentially expressed genes (S100A9 and SERPINB3) were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD. In vitro cell experiments confirmed that WTAP influenced the expression of the 2 candidate differentially expressed genes and promoted primary human epidermal keratinocyte proliferation while inhibiting human epidermal keratinocyte differentiation. Furthermore, we showed that WTAP, S100A9, and SERPINB3 expression correlated with AD severity. Our findings revealed that WTAP-mediated m6A modification promoted the expression of S100A9 and SERPINB3 to aggravate human epidermal keratinocyte proliferation and dysdifferentiation contributing to the pathophysiological development of AD.

Image classification and auxiliary diagnosis system for hyperpigmented skin diseases based on deep learning.

Background and aim: Melasma (ML), naevus fusco-caeruleus zygomaticus (NZ), freckles (FC), cafe-au-lait spots (CS), nevus of ota (NO), and lentigo simplex (LS), are common skin diseases causing hyperpigmentation. Deep learning algorithms learn the inherent laws and representation levels of sample data and can analyze the internal details of the image and classify it objectively to be used for image diagnosis. However, deep learning algorithms that can assist clinicians in diagnosing skin hyperpigmentation conditions are lacking. Methods: The optimal deep-learning image recognition algorithm was explored for the auxiliary diagnosis of hyperpigmented skin disease. Pretrained models, such as VGG-19, GoogLeNet, InceptionV3, ResNet50V2, ResNet101V2, ResNet152V2, InceptionResNetV2, DesseNet201, MobileNet, and NASNetMobile were used to classify images of six common hyperpigmented skin diseases. The best deep learning algorithm for developing an online clinical diagnosis system was selected by using accuracy and area under curve (AUC) as evaluation indicators. Results: In this research, the parameters of the above-mentioned ten deep learning algorithms were 18333510, 5979702, 21815078, 23577094, 42638854, 58343942, 54345958, 18333510, 3235014, and 4276058, respectively, and their training time was 380, 162, 199, 188, 315, 511, 471, 697, 101, and 144 min respectively. The respective accuracies of the training set were 85.94%, 99.72%, 99.61%, 99.52%, 99.52%, 98.84%, 99.61%, 99.13%, 99.52%, and 99.61%. The accuracy rates of the test set data were 73.28%, 57.40%, 70.04%, 71.48%, 68.23%, 71.11%, 71.84%, 73.28%, 70.39%, and 43.68%, respectively. Finally, the areas of AUC curves were 0.93, 0.86, 0.93, 0.91, 0.91, 0.92, 0.93, 0.92, 0.93, and 0.82, respectively. Conclusions: The experimental parameters, training time, accuracy, and AUC of the above models suggest that MobileNet provides a good clinical application prospect in the auxiliary diagnosis of hyperpigmented skin.

Clinical factors associated with remission of obese acanthosis nigricans after laparoscopic sleeve gastrectomy: a prospective cohort study.

BACKGROUND: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. METHODS: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n =178) or OB with AN (OB_AN, n =141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. RESULTS: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels ( P <0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery ( P <0.01). CONCLUSION: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

Ozonated triglyceride protects against septic lethality via preventing the activation of NLRP3 inflammasome. / é ¸åŒ–è„‚è‚ªé ¸é ¯é€šè¿‡æŠ‘åˆ¶NLRP3炎症小体活化减少脓毒症致死（英文）.

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1ß and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS: Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.

Sodium thiosulfate ameliorates atopic dermatitis via inhibiting the activation of NLRP3 inflammasome.

Atopic dermatitis (AD) is a common disease with a considerable impact on the patient's quality of life and limited treatment options. Sodium thiosulfate (STS) is a traditional medicine used in the rescue of cyanide poisoning, and some pruritus dermatosis. However, the exact efficacy and mechanism of its application on AD are not clear. In this work, comparing to other traditional therapy, STS was found to effectively improve the severity of skin lesions and the quality of life in AD patients with a dose-dependent manner. Mechanically, STS downregulated the expression of IL-4, IL-13, IgE in the serum of AD patients, as well as reduce the concentration of eosinophils. Furthermore, in the AD-like mice model triggered by ovalbumin (OVA) and calcitriol, STS was found to reduce the epidermal thickness, scratching times, and the infiltration of dermal inflammatory cells in AD mice, as well as the reactive oxygen species (ROS) production and the expression levels of inflammatory cytokines in the skin tissue. In HacaT cells, STS inhibited the accumulation of ROS and activation of NLRP3 inflammasome and its downstream IL-1ß expression. Therefore, this study revealed that STS plays an important therapeutic role in AD, and the mechanism may be that STS inhibits the activation of NLRP3 inflammasome and the subsequent release of inflammatory cytokines. Thus, the role of STS in treating AD was clarified and the possible molecular mechanism was revealed.

Topical Ozone Accelerates Diabetic Wound Healing by Promoting Re-Epithelialization through the Activation of IGF1R-EGFR Signaling.

Ozonated oil increases the healing of chronic diabetic wounds, but the underlying mechanisms remain unclear. We investigated the effect of topical ozonated oil on wound healing in mice with diabetes with diet-induced obesity and further elucidated the role of EGFR and IGF1R signaling in diabetic wound healing. We found that topical ozonated oil accelerated wound healing; increased phosphorylation of IGF1R, EGFR, and VEGFR; and improved vascularization at the wound leading edge in mice with diabetes with diet-induced obesity. Exposure of normal epidermal keratinocytes to ozonated medium (20 µM for 2 hours daily) increased cell proliferation and migration distance by increasing phosphorylation of IGF1R and EGFR and downstream phosphoinositide 3-kinase, protein kinase B, and extracellular signal-regulated kinase. These findings shed light on the mechanism for topical ozone action in chronic wounds and support its potential therapeutic application.

Evaluating the causality between skin tanning, radiated disorders, and basal cell carcinoma: a multivariable Mendelian randomization analysis.

The causality of ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue with basal cell carcinoma (BCC) remains unclear. Our objective was to investigate whether ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue have a relation with the occurrence and development of BCCs. In this work, independent genetic variants strongly associated (P < 5e-08) with ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for BCC was obtained from the European Bioinformatics Institute (EBI). Two-sample univariable and multivariable Mendelian randomization (MR) were performed. Sensitivity analyses were preformed via MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test. We observed positive causal effect both for ease of skin tanning [odds ratio (OR) = 2.102, 95% confidence interval (CI) = 1.915-2.306, P = 2.71e-55] and radiation-related disorders of the skin and subcutaneous (OR = 1.603, 95% CI = 1.483-1.734, P = 3.41e-32) on occurrence of BCCs based on univariable MR analyses. In the multivariable mendelian randomization (MVMR) analysis of BCC risk, we also observed a direct causal effect of ease of skin tanning (ORMVMR = 1.623, 95% CI = 1.445-1.824, PMVMR =3.41e-16) and radiation-related disorders of the skin and subcutaneous (ORMVMR = 1.208, 95% CI = 1.107-1.319, PMVMR = 2.46e-05) on BCCs. The findings suggest that the high risk of BCCs can be attributed to ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue.

Critical role of epigenetic modification in the pathogenesis of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease characterised by recurrent eczema-like lesions and severe pruritus, along with drying and decrustation of skin. Current research relates the pathogenesis of atopic dermatitis mainly to genetic susceptibility, abnormal skin barrier function, immune disorders, Staphylococcus aureus colonisation, microbiological dysfunction and vitamin D insufficiency. Epigenetic modifications are distinct genetic phenotypes resulting from environment-driven changes in chromosome functions in the absence of nuclear DNA sequence variation. Classic epigenetic events include DNA methylation, histone protein modifications and non-coding RNA regulation. Increasing evidence has indicated that epigenetic events are involved in the pathogenesis of atopic dermatitis by their effects on multiple signalling pathways which in turn influence the above factors. This review primarily analyses the function of epigenetic regulation in the pathogenesis of atopic dermatitis. In addition, it tries to make recommendations for personalised epigenetic treatment strategies for atopic dermatitis in the future.

Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway. / 医用臭氧油通过抑制FcεRI/Syk信号通路缓解DNCB诱导的变应性接触性皮炎（英文）.

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1ß, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1ß, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS: Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.

Protective roles of tRNA-derived small RNA tRF-Ile-AAT-019 in pathological progression of psoriasis.

Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. Transfer RNA fragments (tRFs) are tRNA-derived small RNAs (tsRNAs), which possess regulatory functions in many diseases. Their potential roles in the pathological development of psoriasis have not been established. We first identified differentially expressed (DE) tRFs from psoriatic skin lesions using small RNA sequencing, and collected additional clinical samples for validation. Then, we investigated the function and mechanism of target tRFs in vitro. As a result of our investigation: we identified 234 DE transcripts in psoriatic skin lesions compared with normal controls. Further functional analysis showed the downregulation of tRF-Ile-AAT-019 in psoriatic lesions plays a critical role in pathogenesis since it could target 3'UTR of the serine protease serpin protein E1 (SERPINE1) gene. We next demonstrated that tRF-Ile-AAT-019 could suppress SERPINE1, thus leading to decreased expressions of vascular endothelial growth factor but increased expressions of keratinocytes (KCs) differentiation markers including Keratin1 and Involucrin. In conclusion, tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1, resulting in regulation of KCs differentiation and vascular proliferation biomarkers and providing a potential novel targeting pathway for the disease treatment.