Efficacy of noninvasive multisource radiofrequency treatment on periorbital rhytids using an imaging device.

OBJECTIVE: To evaluate the efficacy of the multisource radiofrequency in periorbital wrinkles treatment using a VISIA imager. METHODS: This is a prospective cohort study involving 30 sites in 15 patients. INCLUSION CRITERIA: healthy subjects with periorbital wrinkles. Patients underwent five treatment sessions for each site using multisource radiofrequency. VISIA imager was used before and after each treatment, and in 12-week follow-up. The wrinkle scores were calculated and compared between baseline and 12-week follow-up. Changing in periorbital wrinkles were evaluated by blinded dermatologist using a scale of 0-3. After the study, patients rated their satisfaction using a scale of 0-3. The study protocol was approved by our institutional human research review committee, according to the ethics guideline of Helsinki (1975). RESULTS: The effect of treatment on subjects on follow-up compared to baseline showed a highly significant difference with P-values <0.05. Only two patients had no improvement according to blind dermatologist assessment of photographs. Thirteen patients reported satisfaction scale between 1 and 3. CONCLUSIONS: The multisource radiofrequency is safe and effective in reducing periorbital rhytids, and with the help of VISIA imager we can get more objective data to evaluate the efficacy of radiofrequency treatment on the periorbital areas. Lasers Surg. Med. 51:251-255, 2019. © 2018 Wiley Periodicals, Inc.

Multi-wavelength laser treatments of spider nevi.

Spider nevi (SN) are one of common vascular diseases. Different treatment techniques have been described for SN previously, including electrocoagulation, argon laser, pulsed dye lasers (PDL), pulsed potassium titanylphosphate laser (KTP), and 1064-nm neodymium yttrium-aluminum-garnet (Nd:YAG) laser. These methods are effective but may require good technical management, multiple treatments, and often result in scarring or pigmentation. Multi-wavelength laser combined with 595-nm PDL followed by 1064-nm Nd:YAG and can be selectively absorbed by hemoglobin in vessels. The 595-nm laser can target shallow vessels whereas the 1064-nm laser may target deeper vessels due to the different penetration capacities of these wavelengths. Moreover, Nd:YAG absorption is remarkable increased following by PDL treatment. Multi-wavelength laser treatments have been successfully used for vascular diseases but there is little experience in SN therapy. Consequently, these treatment parameters have not been established for SN, particularly in Asian patients with Fitzpatrick skin type (FST) IV. Report experience with using multi-wavelength laser for SN treatment in Asian patients with FST IV. Forty-three SN lesions received multi-wavelength laser treatments via a PDL followed by an Nd:YAG laser. The treatment was performed at 7 mm spot size at 9.5-11 J/cm2, 10 ms with PDL, followed by Nd:YAG at 40-50 J/cm2, 15 ms. The laser treatments were performed with a single pass without overlap. Complete resolution was observed in 40 lesions and an 80-90% improvement in the other three lesions after one treatment session. One patient had superficial scarring. Four patients had hyperpigmentation that resolved within 3 months. Multi-wavelength laser treatments are fast and effective interventions for SN treatment in Asian patients with minimal adverse effects when appropriate parameters are set.

Skin healing and collagen changes of rats after fractional erbium:yttrium aluminum garnet laser: observation by reflectance confocal microscopy with confirmed histological evidence.

The fractional erbium:yttrium aluminum garnet (Er:YAG) laser is widely applied. Microstructural changes after laser treatment have been observed with histopathology. Epidermal and dermal microstructures have also been analyzed using reflectance confocal microscopy (RCM). However, no studies have compared these two types of microstructural changes in the same subject at multiple time points after irradiation, and it is unclear if these two types of changes are consistent. We use RCM to observe the effect of different laser energies on skin healing and collagen changes in the skin of Sprague-Dawley rats that had been irradiated by fractional Er:YAG lasering at different energies. RCM was used to observe skin healing and detect collagen changes at different time points. Collagen changes were observed using hematoxylin and eosin (H&E) staining and quantitatively analyzed by western blot. RCM showed that, irrespective of laser energy, microscopic treatment zones (MTZs) were larger at 1 day after irradiation. The MTZs then reduced in size from 3 to 7 days after irradiation. The higher the energy, the larger the MTZ area. The amount of collagen also increased with time from 1 day to 8 weeks. However, the increase in the collagen amount on both RCM and H&E staining was not influenced by the laser energy. Western blotting confirmed that the amount of type I and type III collagens increased over time, but there were no significant differences between the different energy groups (p > 0.05). In conclusion, RCM is a reliable technique for observing and evaluating skin healing and collagen expression after laser irradiation.

Recent advances in targeted nanoparticles drug delivery to melanoma.

Melanoma is one of the most aggressive skin cancers, notorious for its high multidrug resistance and low survival rate. Conventional therapies (e.g., dacarbazine, interferon-alpha-2b and interleukin-2) are limited by low response rate and demonstrate no overall survival benefit. Novel targeted therapies (e.g., vemurafenib, dabrafenib and trametinib) have higher initial response rate and clear impact on the overall survival, but relapse usually occurs within 6 to 9 months. Although immunotherapy (e.g., ipilimumab, pembrolizumab and nivolumab) can achieve long-term and durable response, rate of adverse events is extremely high. With the development of nanotechnology, the applications of nanocarriers are widely expected to change the landscape of melanoma therapy for foreseeable future. In this review, we will relate recent advances in the application of multifunctional nanocarriers for targeted drug delivery to melanoma, in melanoma nanotheranostics and combination therapy, and nanopharmaceutical associated melanoma clinical trials, followed by challenges and perspectives. From the clinical editor: The team of authors describes the current treatment regimes of malignant melanoma emphasizing the importance of achieving a better efficacy and the need to develop a better understanding of melanoma tumorigenesis.

Association of rs10954213 polymorphisms and haplotype diversity in interferon regulatory factor 5 with systemic lupus erythematosus: a meta-analysis.

The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.

Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels.

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.

Clinical and dermoscopic variation of basal cell carcinoma according to age of onset and anatomic location: a multicenter, retrospective study.

Basal cell carcinoma (BCC) is rare in young individuals and reported to possess different pathogenetic, clinical and histological features from late-onset BCC. However, the dermoscopic variability of BCC according to age of onset has not been investigated. Anatomic location was revealed to be associated with dermoscopic variation of BCC in Western population, but whether it applies to Asian population remains unknown. We evaluated the clinical and dermoscopic features of 448 BCCs and compared each feature by age of onset (age < 50/ > 50 years) and anatomic location. Early-onset BCCs occurred more frequently on non-sun-exposed sites (OR 3.28, P = 0.001) and were less pigmented than late-onset BCCs (P = 0.003). Blue-gray globules (OR 1.74, P = 0.037) and no vessels (OR 2.04, P = 0.021) were independently associated with early-onset BCCs, whereas arborizing telangiectasia (OR 0.30, P < 0.001), large blue-gray ovoid nests (OR 0.38, P < 0.001) and ulceration (OR 0.33, P < 0.001) were less common in early-onset BCCs. Scalp BCCs were significantly more pigmented than BCCs located elsewhere (P = 0.022). Superficial subtype (OR 5.90, P < 0.001), spoke-wheel areas (OR 4.78, P = 0.034), superficial erosions (OR 4.69, P = 0.003) and polymorph vessels (OR 6.86, P = 0.001) were independently associated with trunk BCCs, whereas nodular subtype (OR 5.48, P < 0.001) and arborizing telangiectasias (OR 3.64, P < 0.001) with BCCs on face and neck. Our findings suggest that age of onset and anatomic location are independent factors affecting the dermoscopic appearance of BCC.

Risk factors of long-term alopecia after pulsed-dye laser treatment for infantile scalp hemangiomas: A retrospective study.

Pulsed-dye laser (PDL), as an effective and frequently-used treatment modality for infantile hemangiomas (IH), could render patients at risk of developing long-term alopecia. Data on alopecia caused by PDL treatment remain scant and the contributing factors are not clear. Our objective was to identify the risk factors associated with long-term alopecia resulting from PDL treatment for scalp IH. We conducted a retrospective study incorporating patients with IH diagnosis and PDL intervention via thoroughly reviewing the clinical database of the dermatology department. Scalp IH patients were further screened and their medical records were collected. Long-term alopecia was defined as no signs of terminal hair regrowth for at least 2 years in this study. Of the 1293 IH patients, 47 (14 boys and 33 girls) with a mean age of 4.5 months (standard deviation, 3.2) were diagnosed as scalp IH and had subsequently undergone PDL treatments. Hair growth in the treatment area of 18 patients (38.3%) nearly returned to normal, 22 patients (46.8%) had varying degrees of hair loss, and seven patients (14.9%) had no hair regrowth (long-term alopecia). Compared with the older patients receiving treatment, IH patients younger than 3 months who started PDL treatment had a higher risk of developing long-term alopecia (odds ratio, 30.833; 95% confidence interval, 4.079-232.025; p = 0.01). The total number of PDL sessions, post-treatment blisters, and location of IH were not shown to be significantly associated with the development of long-term alopecia. Collectively, our study provides an important insight into curating treatments for IH in infants younger than 3 months. PDL treatments for scalp IH may perhaps be avoided or delayed to prevent the development of treatment-associated long-term alopecia.

Molecular Cloning and Expression Profile of Class E Genes Related to Sepal Development in Nelumbo nucifera.

The lotus (Nelumbo Adans.) is an important aquatic plant with ornamental, medicinal and edible values and cultural connotations. It has single-, semi-double-, double- and thousand-petalled types of flower shape and is an ideal material for developmental research of flower doubling. The lotus is a basal eudicot species without a morphological difference between the sepals and petals and occupies a critical phylogenetic position in flowering plants. In order to investigate the genetic relationship between the sepals and petals in the lotus, the class E genes which affect sepal formation were focused on and analyzed. Here, SEPALLATA 1(NnSEP1) and its homologous genes AGAMOUS-LIKE MADS-BOXAGL9 (NnAGL9) and MADS-BOX TRANSCRIPTION FACTOR 6-like (NnMADS6-like) of the class E gene family were isolated from the flower buds of the Asian lotus (Nelumbo nucifera Gaertn.). The protein structure, subcellular localization and expression patterns of these three genes were investigated. All three genes were verified to locate in the nucleus and had typical MADS-box characteristics. NnSEP1 and NnMADS6-like were specifically expressed in the sepals, while NnAGL9 was highly expressed in the petals, suggesting that different developmental mechanisms exist in the formation of the sepals and petals in the lotus. The significant functional differences between NnSEP1, NnMADS6-like and NnAGL9 were also confirmed by a yeast two-hybrid assay. These results expand our knowledge on the class E gene family in sepal formation and will benefit fundamental research on the development of floral organs in Nelumbo.

RasGRP3 in peripheral blood mononuclear cells is associated with disease activity and implicated in the development of systemic lupus erythematosus.

This study examined the relationship between the expression of Ras guanyl nucleotide-releasing protein 3 (RasGRP3) and disease activity in systemic lupus erythematosus (SLE) and explored the possible mechanisms in MRL/lpr mice. We detected the expression of RasGRP3 in peripheral blood mononuclear cells (PBMCs) of SLE patients (n=26) and healthy controls (n=20) by employing RT-PCR and studied the association between the mRNA expression of RasGRP3 in PBMCs and the clinical findings. We also measured the protein level of RasGRP3 in PBMCs by Western blotting (n=10). In addition, we isolated the B cells from PBMCs with magnetic bead separation and determined the RasGRP3 expression by RT-PCR (n=10). Furthermore, we extracted spleen B cells from MRL/lpr mice and knocked down RasGRP3 by siRNA transfection to study the role of RasGRP3 in the pathway of B cell receptor (BCR) activation and the production of pro-inflammatory cytokines. Compared with healthy volunteers, the expression of RasGRP3 was significantly elevated in PBMCs and purified B cells from SLE patients. The mRNA expression of RasGRP3 in PBMCs was positively correlated with SLE disease activity index (SLEDAI). Moreover, silencing RasGRP3 could inhibit Akt and Erk1/2 activation in marginal zone (MZ) and follicular (FO) B cells of MRL/lpr mice. Additionally, the production of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), was decreased whereas activation of caspase-3 cleavage was induced in vitro. In conclusion, over-expression of RasGRP3 is associated with disease activity and might be involved in the pathogenesis of SLE.

The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhi Regulatory B-Cell Subset in Lupus.

IL-35 is a critical immunosuppressive cytokine that plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in systemic lupus erythematosus, also a dichotomous regulator for B-cell immune responses, has an effect on IL-35-producing regulatory B cells and their underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Faslpr/lpr mice. BAFF-induced IL-35-producing B cells were mainly from the marginal zone B-cell subset and exhibited a CD5+CD1dhiFcγRIIbhi phenotype. These IL-35-producing regulatory B-cell subsets exhibited regulatory effects on both CD4+CD25- T cells and CD4+CD25+ regulatory T cells. We further identified that BAFF-TACI interaction could induce the production of IL-35 through the classical NF-κB1 pathway. In vivo study also showed that BAFF could facilitate IL-35 secretion in marginal zone B cells, whereas anti-BAFF treatment could decrease the frequency of IL-35-producing CD5+CD1dhiFcγRIIbhi B cells in MRL-Faslpr/lpr mice. We showed that BAFF could induce IL-35 production by a unique CD5+CD1dhiFcγRIIbhi regulatory B-cell subset mainly through TACI activation in lupus, providing an advanced understanding of the regulatory effect of BAFF in autoimmune diseases.