Efficacy and safety of non-surgical short-wave radiofrequency treatment of mild-to-moderate erythematotelangiectatic rosacea: a prospective, open-label pilot study.

Although various treatments have been proposed for the management of rosacea, achieving complete remission of persistent erythema remains challenging. Short-wave radiofrequency (SWRF) treatment has been shown to repair skin barriers and reduce chronic inflammation. However, limited studies have evaluated the effectiveness of SWRF treatment for erythematotelangiectatic rosacea (ETR). A prospective, open-label pilot study using SWRF therapy was conducted on 30 patients with mild-to-moderate ETR. During the first stage, the patients underwent a single, full-face treatment and were evaluated before and after the session, as well as on the 7th and 15th day post-treatment. During the second stage, ten treatment sessions were administered, and the patients were evaluated before and after the tenth session, as well as 1 month after the treatment. Adverse events were recorded during each treatment session, and the patients were followed up for 3 months after the last session. Twenty-eight patients completed the entire trial. On the 7th day after the single treatment, the global score (total score of flushing, persistent erythema, and telangiectasia) of ETR improved from 5.23 ± 1.09 to 4.00 ± 0.76 relative to the baseline value (p < 0.05); moreover, the overall treatment satisfaction improved from 7.27 ± 0.89 to 4.90 ± 0.91 (p < 0.05). 1 month after the tenth treatment session, the global score improved from 5.30 ± 1.01 to 3.85 ± 0.93 (p < 0.05), and the overall treatment satisfaction improved from 7.13 ± 0.85 to 5.17 ± 1.19 (p < 0.05). During the 3 month follow-up period, there were two cases of recurrence. Therefore, this report indicates that SWRF might be an effective auxiliary treatment for mild-to-moderate ETR.

Efficacy and safety of non-insulated fractional microneedle radiofrequency for treating difficult-to-treat rosacea: a 48-week, prospective, observational study.

Rosacea is a common chronic facial inflammatory skin disease. However, treatment for "difficult-to-treat rosacea" cases has not been established. This 48-week, prospective, observational study analyzed patients who underwent three non-insulated fractional microneedle radiofrequency (NFMRF) sessions at 2-month intervals. Therapy efficacy, epidermal barrier function, and side effects were evaluated. 34 subjects completed the trial. NFMRF resulted in CEA score reduction from 2.65 ± 0.59 to 1.56 ± 0.50 (P < 0.001) and mean DLQI reduction from 16.70 ± 3.55 to 10.48 ± 2.92 (P < 0.001). The successes of CEA (44.12 vs. 2.94%), IGA (91.67 vs. 25.00%), and flushing (58.82 vs. 26.47%) were observed. Among 34 patients, 22 reported "excellent" or "good" improvement and 30 were "very" or "relatively" satisfied. Skin barrier results revealed that hemoglobin content significantly decreased from 376.47 ± 71.29 at visit 0 to 161.32 ± 52.86 at visit 3. 2 of 30 patients followed-up at 6 months had a relapse at 18 and 20 weeks, respectively. No serious side effects were observed. NFMRF alone results in visible improvement and has great efficacy for difficult-to-treat rosacea without compromising patient safety or damaging the skin barrier.

Efficacy of non-ablative fractional 1440-nm laser therapy for treatment of facial acne scars in patients with rosacea: a prospective, interventional study.

Acne scarring is one of the most common facial skin disorders. The appropriate treatments for acne scars in patients with rosacea have not been studied. This study was designed to evaluate the efficacy and safety of non-ablative fractional 1440-nm laser (1440-nm NAFL) therapy for treatment of atrophic acne scars in patients with rosacea. In this prospective, interventional study, 32 patients with rosacea and acne scars underwent three sessions of 1440-nm NAFL therapy. Therapy efficacy, epidermal barrier function, and side effects were evaluated. Thirty patients completed and the median acne scar scores significantly reduced from 45 (30, 50) to 15 (15, 30) after three treatments (P < 0.001). The improvement score of acne scars was 2.7 ± 0.7; 22 (73.3%) were satisfied or highly satisfied. The rosacea erythema scores changed from 2.1 ± 0.4 to 1.9 ± 0.5 (P = 0.326), and flushing, burning, and stinging were not worse. The oil content after treatments was significantly reduced (P < 0.001), while there was no significant difference in other indicators of skin barrier function. The quality-of-life score decreased from 17.5 ± 3.8 to 14.1 ± 3.0 (P < 0.001). No serious side effects were observed. The 1440-nm NAFL therapy is effective in the treatment of acne scaring in patients with rosacea with little damage to the skin barrier.

Association between rosacea and cardiometabolic disease: A systematic review and meta-analysis.

BACKGROUND: Rosacea is recognized as a chronic inflammatory cutaneous disorder associated with multiple systemic illnesses. However, the association between rosacea and cardiometabolic disease (CMD) remains controversial. OBJECTIVE: To evaluate the association between rosacea and CMD by a systematic review and meta-analysis. METHODS: A comprehensive search of studies published before October 16, 2019, was performed in databases of PubMed, Embase, Cochrane Library, and Web of Science. The pooled risk ratios or standardized mean differences were calculated. RESULTS: Thirteen studies were included, representing 50,442 patients with rosacea. Patients with rosacea had higher prevalence of dyslipidemia, higher prevalence of hypertension, higher total cholesterol, higher low-density lipoprotein, higher triglycerides, higher systolic blood pressure, higher diastolic blood pressure, and higher fasting blood glucose. Rosacea was not associated with ischemic heart disease, stroke, diabetes, and high-density lipoprotein. LIMITATIONS: No subgroup analysis could be performed according to the subtypes and severity of rosacea. CONCLUSIONS: Rosacea showed a correlation with hypertension and dyslipidemia but not with ischemic heart disease, stroke, or diabetes. We advocate screening for CMD indicators among patients with rosacea, which may be helpful for diagnosis and appropriate treatment at an early stage of disease.

Effects of skin care habits on the development of rosacea: A multi-center retrospective case-control survey in Chinese population.

BACKGROUND: Certain cosmetic habits may trigger or aggravate rosacea, while there is little published epidemiologic evidence to support this point. PURPOSE: To examine if daily skin care habits have an effect on the development of rosacea in Chinese population. METHODS: A multi-center retrospective case-control survey of 1,245 rosacea cases and 1,538 skin-healthy controls was conducted in China. Participants completed the questionnaire comprised of demographic characteristics, socioeconomic data and daily skin care habits. Data were collected retrospectively and analyzed using the chi-square test and t-test. Multivariate logistic regression analyses were used to predict rosacea. RESULTS: The multivariate logistic regression analysis highlighted some results: Dry, oily or mixed skin (OR = 6.3-6.9, P< .001), the usage of foaming cleanser (OR = 1.45, 95%CI 1.115-1.886, P = .01), make up more than 6 times a week (OR = 2.839, 95%CI 1.962-4.108, P< .001), using facial mask more than 4 times a week (OR = 2.56-3.069, P< .001), facial treatments at beauty salon more than once a week (OR = 4.946, 95%CI 2.005-12.198, P = .0018) and using beauty salon products (OR = 2.334, 95%CI 1.435-3.976, P = .0018) are positively correlated with the development of rosacea. Using of moisturizing products (OR = 0.602, 95%CI 0.386-0.983, P = .035) and sunscreen cream (OR = 0.303-0.507, P< .001 or P = .0167 for different frequency) presented significantly negative correlations with rosacea. Frequency of cleansing showed a nonlinear association with rosacea: using facial cleansers 1~3 times per week (OR = 0.647, 95%CI 0.429-0.975, P = .038) showed beneficial effects while using facial cleanser excessively (twice or more daily) (OR = 2.131, 95%CI 1.394-3.256, P< .001) positively correlated to rosacea strongly. CONCLUSIONS: Excessive use of facial cleanser (twice or more a day) and facial mask (more than 4 times a week), frequent makeup (more than 6 times a week), regular skin care in beauty salon (more than once a week), and using beauty salon products were closely correlated to the development of rosacea in Chinese population.

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial.

Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.

Relationship between rosacea and dietary factors: A multicenter retrospective case-control survey.

Although patients with rosacea often consult dermatologists for dietary factors that might be related to their skin disorders, few studies have been conducted to research the relationship between rosacea and dietary factors. The purpose of this study was to evaluate the potential relationship between rosacea and diet among the large Chinese population with rosacea, which would provide dietary guidelines for patients with rosacea. A multicenter case-control study was conducted. The feeding frequency 2 years before the occurrence of rosacea was collected by standardized questionnaires. Multiple logistic regression analysis was used to calculate risks related to the diet. One thousand three hundred and forty-seven patients with rosacea and 1290 controls were enrolled in our study. We found that high-frequency intake of fatty food and tea presented a positive correlation with rosacea, while high-frequency dairy product intake showed significant negative correlation with rosacea. Sweet food, coffee and spicy food appeared to be independent of any subset of rosacea in our study. However, high-frequency dairy product intake showed a borderline beneficial effect on rosacea severity. We further analyzed the correlation between diet and the subtype of rosacea. We found that high-frequency fatty intake was associated with erythematotelangiectatic rosacea (ETR) and phymatous rosacea, while high-frequency tea intake was only associated with ETR. In addition, high-frequency dairy product intake showed negative correlations with ETR and papulopustular rosacea. Rosacea is associated with some dietary factors, and our study is valuable in establishing dietary guidelines to prevent and improve rosacea.

Microrna-217 modulates human skin fibroblast senescence by directly targeting DNA methyltransferase 1.

DNA methyltransferase 1 (DNMT1) is a major epigenetic regulator associated with many biological processes. However, the roles and mechanisms of DNMT1 in skin aging are incompletely understood. Here we explored the role of DNMT1 in human skin fibroblasts senescence and its related regulatory mechanisms. DNMT1 expression decreased in passage-aged fibroblasts and DNMT1 silencing in young fibroblasts induced the senescence phenotype. MiR-217 is predicted to target DNMT1 mRNA and miR-217 expression increased in passage-aged fibroblasts. MiR-217 directly targeted the 3'-untranslated region (3'-UTR) of DNMT1 in HEK 293T cells and inhibited DNMT1 expression in fibroblasts. MiR-217 overexpression induced a senescence phenotype in young fibroblasts, and miR-217 downregulation in old HSFs partially reversed the senescence phenotype. However, these effects could be significantly rescued by regulating DNMT1 expression in fibroblasts. After regulating miR-217 levels, we analyzed changes in the promoter methylation levels of 24 senescent-associated genes, finding that 6 genes were significantly altered, and verified p16 and phosphorylated retinoblastoma (pRb) protein levels. Finally, an inverse correlation between DNMT1 and miR-217 expression was observed in skin tissues and different-aged fibroblasts. Together, these findings revealed that miR-217 promotes fibroblasts senescence by suppressing DNMT1-mediated methylation of p16 and pRb by targeting the DNMT1 3'-UTR.

miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1.

Skin aging is a complicated physiological process and epigenetic feature, including microRNA-mediated regulation and DNA methylation, have been shown to contribute to this process. DNA methylation is regulated by DNA methyltransferase, of which DNA methyltransferase 1 (DNMT1) is the most abundantly known. But evidence supporting its role in skin aging remains scarce, and no report regards its specifical upstream-regulating molecules in the process of skin aging so far. Here, we found that DNMT1 expression was markedly higher in young human skin fibroblasts (HSFs) than that in passage-aged HSFs, and DNMT1 knockdown significantly induced the senescence phenotype in young HSFs. We predicted the upstream miRNAs which could regulate DNMT1 with miRNA databases and found miR-377 had high homology with a sequence in the 3'-UTR of human DNMT1 mRNA. We confirmed that miR-377 was a potential regulator of DNMT1 by luciferase reporter assays. miR-377 expression in passage-aged HSFs was markedly higher than that in the young HSFs. miR-377 overexpression promoted senescence in young HSFs, and inhibition of miR-377 reduced senescence in passage-aged HSFs. Moreover, these functions were mediated by targeting DNMT1. Microfluidic PCR and next-generation bisulfite sequencing of 24 senescent-associated genes' promoters revealed alterations of the promoter methylation levels of FoxD3, p53, and UTF1 in HSFs treated with miR-377 mimics or inhibitors. We also verified that the miR-377-mediated changes in p53 expression could be reversed by regulation of DNMT1 in HSFs. Similarly, there was a negative correlation between miR-377 and DNMT1 expression in young and photoaged HSFs, HSFs, or skin tissues from UV-unexposed areas of different aged donors. Our results highlight a novel role for miR-377-DNMT1-p53 axis in HSF senescence. These findings shed new light on the mechanisms of skin aging and identify future opportunities for its therapeutic prevention.

G protein-coupled estrogen receptor enhances melanogenesis via cAMP-protein kinase (PKA) by upregulating microphthalmia-related transcription factor-tyrosinase in melanoma.

OBJECTIVE: This study investigated the role and mechanism of action of G protein-coupled estrogen receptor (GPER) in melanogenesis. METHODS: GPER expression was detected in the A375 human melanoma cell line and B16 mouse melanoma cell line. Cell proliferation, melanin content, tyrosinase (TYR) activity, cyclic adenosine monophosphate (cAMP) level, and TYR and microphthalmia-related transcription factor (MITF) expression were measured. GPER activation was altered by agonist and antagonist treatment and its expression was downregulated by gene silencing. Estradiol-induced melanin synthesis and the activation of related signaling pathways were suppressed by inhibiting GPER via antagonist treatment. The relationship between GPER and TYR was evaluated in clinical chloasma samples by immunohistochemistry. RESULTS: Upregulation of GPER in A375 cells promoted melanogenesis, favored as indicated by increases in TYR and MITF expression and TYR activity. GPER activated melanin production via the cAMP-protein kinase (PK) A pathway, suggesting that GPER plays an important role in estrogen-induced melanin synthesis. The effect of GPER activation on cAMP-MITF-TYR signaling was also demonstrated in B16 cells. A significant association was observed between GPER and TYR expression in chloasma skin lesions relative to normal skin. CONCLUSION: GPER enhances melanin synthesis via cAMP-PKA-MITF-TYR signaling and modulates the effects of estrogen in melanogenesis. GPER is therefore a potential drug target for chloasma treatment.

Induction of melasma by 1064-nm Q-switched neodymium:yttrium-aluminum-garnet laser therapy for acquired bilateral nevus of Ota-like macules (Hori nevus): A study on related factors in the Chinese population.

Laser treatment has emerged as a common treatment modality for acquired bilateral nevus of Ota-like macules (ABNOM). To identify the ratio of melasma induction and exacerbation before and after laser therapy for ABNOM and to observe the risk factors related to the induction and exacerbation of melasma by laser therapy, we analyzed related factors of 1268 adult Chinese patients who underwent 1064-nm Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (QNYL) treatment using case series and case-control studies. Overall, 24.0% of the ABNOM patients had mixed melasma. Among the ABNOM patients without melasma, after laser therapy the development of melasma was more frequently noted in patients older than 35 years (P < 0.0001), as well in patients whose ABNOM was less than 10 cm(2) (P = 0.027), ABNOM were light (similar to yellow-brown) in color (P = 0.021) and skin types were closer to type IV (P < 0.0001). New melasma lesions also appeared most frequently in the zygomatic region (P < 0.0001). Among the ABNOM patients with melasma, 89.5% experienced worsening of their melasma, irrespective of their related factors above. We concluded that the risk of inducing melasma is great after 1064-nm QNYL treatment in ABNOM patients, and particularly in the patients with both ABNOM and melasma. ABNOM patients should be treated as early as possible and before the age of 35 years.

A Split-Face Study of Dual-Wavelength Laser on Neck and Facial Port-Wine Stains in Chinese Patients.

BACKGROUND: Although pulsed dye laser (PDL) has long been regarded as the gold standard in treating port-wine stain (PWS), advanced PWS with deeper coloration may display resistance because of limited penetration depth of 585 or 595-nm light. Recently, a dual-wavelength laser system has been reported to achieve pronounced fading in many patients. OBJECTIVE: The objective was to evaluate the efficacy and safety of a dual-wavelength laser device in treatment of neck and facial PWS in a direct side-by-side comparison. METHODS: Sixteen Chinese patients with neck and/or facial PWSs were enrolled in the study. All lesions were randomly divided into two area, treated area and adjacent untreated area. Five successive treatments using a dual-wavelength laser system (595-nm PDL combined with 1,064-nm Nd:YAG laser) were delivered on treated areas at 4- to 6-week intervals. The adjacent area was not treated as self control. Two blinded dermatologists evaluated the clinical changes by comparing the before and after photos. Erythema index (EI) values were measured with a non-invasive instrument. RESULTS: After five sessions of treatment, over 62.5% (10/16) patients achieved more than 50% (moderate or significant) improvement. The efficacy maintained at the 3-month follow-up visit. The values of EI on treated area showed a significant decrease. Adverse effects of treated area were limited. CONCLUSION: Using this split-face module, the dual-wavelength laser system is proved to be effective and well tolerated in treating neck and facial PWSs in Chinese patients. Adverse effects were minimal and acceptable.

Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.

To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, P(combined)=8.07 × 10(-12), odds ratio (OR)=1.18), 11q23.3 (rs638893, P(combined)=2.47 × 10(-9), OR=1.22), and 10q22.1 (rs1417210, P(combined)=1.83 × 10(-8), OR=0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, P(combined)=8.57 × 10(-8), OR=0.88), 10p15.1 (rs3134883, P(combined)=1.01 × 10(-5), OR=1.11), and 22q12.3 (rs2051582, P(combined)=2.12 × 10(-5), OR=1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations.

Association study of tumor necrosis factor receptor type 2 M196R and toll-like receptor 2 Arg753Gln polymorphisms with acne vulgaris in a Chinese Han ethnic group.

BACKGROUND: Inflammatory cytokines such as tumor necrosis factor receptor 2 (TNFR2) and Toll-like receptor 2 (TLR2) are the main responsible mediators of inflammatory acne. Factors affecting their production may possibly influence the degree of inflammatory response and hence may account for the clinical severity of acne. However, the roles of TNFR2 and TLR2 in the pathophysiology of acne vulgaris are poorly understood. We therefore investigated the relationship between acne vulgaris susceptibility and the polymorphisms in the TNFR2 M196R as well as TLR2 Arg753Gln gene. METHODS: A total of 93 acne vulgaris patients and 90 healthy subjects from the Chinese Han ethnic group were enrolled in the study. The polymerase chain reaction restriction fragment length polymorphism technique was adopted to analyze the single-nucleotide polymorphisms of the TNFR2 M196R and TLR2 Arg753Gln gene, and to examine the association between acne vulgaris and the polymorphisms in the TNFR2 M196R as well as TLR2 Arg753Gln gene. The relationship between different genotypes and the susceptibility to acne vulgaris was analyzed. RESULTS: There is a significant difference in the frequency of TNFR2 M196R genetic polymorphisms between the moderate-acne to severe-acne subgroups and the control group (p < 0.05), and there is also a significant difference in the frequency of TLR2 Arg753Gln genetic polymorphisms between the severe-acne subgroup and control group (p < 0.05). CONCLUSION: The 196R allele of TNFR2 M196R as well as the 753Gln allele of TLR2 Arg753Gln are risk factors for acne vulgaris in Chinese Han patients, further supporting the contribution of inflammatory cytokines to the pathogenesis of acne.

[Effects of CD147 on the production of matrix metalloproteinase-9 by fibroblasts and the invasion of melanoma cells].

OBJECTIVE: To investigate a possible role of CD147 in the production of matrix metalloproteinase-9 (MMP-9) by fibroblasts and the invasion of melanoma cells. METHODS: We cocultured CD147-expression melanoma cells with fibroblasts and examined the MMP-9 expression of fibroblasts by zymography and the invasion of melanoma cells by transwell invasion assay. RESULTS: MMP-9 expression was enhanced in conditioned media, while cocultured with melanoma cells in a dose-dependent manner, and CD147 antibody inhibited the production of MMP-9 in the fibroblasts. When fibroblasts were cultured at the bottom of the lower compartment of transwell invasion model, the number of melanoma cells that invaded significantly increased. Addition of anti-CD147 antibody to the upper compartment transwell invasion model resulted in the significant inhibition of the melanoma cell invasion in reconstituted basement membrane. CONCLUSION: CD147 expressed in melanoma cells plays an important role in the melanoma cell invasion by stimulating the production of MMP-9 by fibroblasts.

[Amplification of beta-catenin gene in the paraffin-embedded epidermal tissue].

OBJECTIVE: To establish a method of extracting DNA from the paraffin-embedded epidermal tissue and examine the amplification of beta-catenin gene by polymerase chain reaction (PCR) analysis. METHODS: Exon 3 of the beta-catenin gene was amplified by PCR in 14 paraffin-embedded Bowen's disease (BD) of various weight and years. RESULTS: The amplification of exon 3 of beta-catenin gene was successful in all the 10 mg and 20 mg samples, but not in the 5 mg samples. The amplification of exon 3 of beta-catenin gene was successful in 9 samples embedded within 10 years, and in only 2 of the 5 samples embedded more than 10 years. CONCLUSION: Epidermal tissue whose weight is 10 mg or more within 10 years of embedding can be used in the amplification of purpose gene by PCR.