Efficacy of Photodynamic Therapy for the Treatment of Bowen's Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Photodynamic therapy is an established treatment option for Bowen's disease. Our meta-analysis was aimed at evaluating the efficacy and recurrence of photodynamic therapy or other topical treatments (5-fluorouracil, cryotherapy) and of photodynamic therapy alone or in combination with other therapies (ablative fractional CO2 laser or plum-blossom needle) for the treatment of Bowen's disease. METHODS: Trials that met our inclusion criteria were identified from PubMed, EMBASE, Web of Science, and Cochrane Library databases, and meta-analyses were conducted with RevMan V.5.4. The risk of bias was estimated with the Cochrane Collaboration's risk of bias tools. Complete response rate, recurrence, pain/visual analogue scale score, cosmetic outcome, and adverse events were considered as outcomes. RESULTS: Of the 2,439 records initially retrieved, 8 randomized controlled trials were included in this meta-analysis. According to our analyses, photodynamic therapy exhibited a significantly higher complete response rate (RR = 1.36, 95% CI [1.01, 1.84], I2 = 86%, p = 0.04), less recurrence (RR = 0.53, 95% CI [0.30, 0.95], I2 = 0%, p = 0.03), and better cosmetic outcome (RR = 1.34, 95% CI [1.15, 1.56], I2 = 0%, p = 0.0002) compared with other treatments. Moreover, there was a significant difference between the complete response rate of photodynamic therapy combined with ablative fractional CO2 laser and that of photodynamic therapy (RR = 1.85, 95% CI [1.38, 2.49], I2 = 0%, p < 0.0001). Photodynamic therapy combined with ablative fractional CO2 laser or plum-blossom needle also showed significantly less recurrence (RR = 0.21, 95% CI [0.09, 0.51], I2 = 0%, p = 0.0005) and a lower visual analogue scale score (RR = 0.51, 95% CI [0.06, 0.96], I2 = 0%, p = 0.03) than photodynamic therapy alone. However, there was no significant difference in the complete response rate between photodynamic therapy combined with ablative continuous CO2 laser and photodynamic therapy combined with ablative fractional CO2 laser (RR = 1.00, 95% CI [0.54, 1.86], I2 not applicable, p = 1.00). CONCLUSIONS: This meta-analysis shows that photodynamic therapy can be used in the treatment of Bowen's disease with better efficacy, less recurrence, and better cosmetic outcomes than cryotherapy and 5-FU. Some methods, including ablative fractional CO2 laser, can be applied in combination with photodynamic therapy to improve efficacy. However, which laser-assisted photodynamic therapy scheme has the most advantages in the treatment of Bowen's disease warrants further exploration.

DIRAS2 Is a Prognostic Biomarker and Linked With Immune Infiltrates in Melanoma.

Background: Skin cutaneous melanoma (SKCM) is a highly malignant skin tumor. DIRAS2 is considered to be a tumor suppressor gene; however, its function in SKCM has not been explored. Methods: The Gene Expression Profiling Interactive Analysis (GEPIA) was implemented to investigate the expression of DIRAS2 in SKCM, and plot the survival curve to determine the effect of DIRAS2 on the survival rates of SKCM patients. Then, the correlation between DIRAS2 and tumor immune infiltration was also discussed, and the expression of DIRAS2 and immune infiltration level in SKCM immune cells was determined using TIMER. The top 100 genes most associated with DIRAS2 expression were used for functional enrichment analysis. In order to confirm the anti-cancer effects of DIRAS2 in SKCM in the data analysis, in vitro assays as well as in vivo studies of DIRAS2 on SKCM tumor cell proliferation, migration, invasion, and metastasis were conducted. Western blot and immunofluorescence assay were employed to study the relationship between DIRAS2 and Wnt/ß-catenin signaling pathway in SKCM. Results: DIRAS2 expression was shown to be significantly correlated with tumor grade using univariate logistic regression analysis. DIRAS2 was found to be an independent prognostic factor for SKCM in multivariate analysis. Of note, DIRAS2 expression levels were positively correlated with the infiltration levels of B cells, CD4+ T cells, and CD8+ T cells in SKCM. The infiltration of B cells, CD4+ T cells, and CD8+ T cells was positively correlated with the cumulative survival rate of SKCM patients. In vitro experiments suggested that proliferation, migration, invasion, and metastasis of SKCM tumor cells were distinctly enhanced after DIRAS2 knockdown. Furthermore, DIRAS2 depletion promoted melanoma growth and metastasis in vivo. As for the mechanism, silencing DIRAS2 can activate the signal transduction of the Wnt/ß-catenin signaling pathway. Conclusion: DIRAS2 functions as a tumor suppressor gene in cases of SKCM by inhibiting the Wnt/ß-catenin signaling. It is also associated with immune infiltration in SKCM.

The Precipitation Behavior of a Cu-Ni-Si Alloy with Cr Addition Prepared by Heating-Cooling Combined Mold (HCCM) Continuous Casting.

A Cu-Ni-Si alloy containing (Ni + Si) ≥ 5 wt.%, with the addition of Cr, is fabricated by HCCM continuous casting and two steps of aging treatment. The evolution of the microstructures and precipitations, as well as the effect of Cr atoms, is studied in this paper. An excellent combination of mechanical property (hardness HV 250-270) and electrical conductivity (46-47 %IACS) is obtained by the first step aging at 500 °C for 0.25 h and the second step aging at 450 °C for 1 h. The cold rolling and aging process are directly conducted on the solution treated specimens fabricated by HCCM continuous casting process without hot deformation, since the excellent homogeneity of matrix is obtained by solution treatment with δ-Ni2Si precipitates dissolved. It is found that the formation of discontinuous precipitation is suppressed by the formation of Cr3Si cores of 5-10 nm before the formation δ-Ni2Si. Then, the nucleation and growth of δ-Ni2Si precipitates occurs around the boundaries of these Cr3Si cores, leading to an enhanced nucleation rate. This study provides a promising direction for the design and optimization of Cu-Ni-Si alloys based on the further understanding of the effect of the addition of Cr.

Induction of T helper 17 cell response by interleukin-7 in patients with primary cutaneous melanoma.

Interleukin (IL)-7 plays a vital role in proliferation and activation of T cells, however, its signaling through CD127 is impaired in T cells in cancers and chronic infections. The mechanisms underlying T helper 17 (Th17) cell responses by IL-7 in melanoma remain not fully understood. The aim of this study was to assess the effect of IL-7 signaling on Th17 responses in patients with primary cutaneous melanoma. Healthy and primary cutaneous melanoma donors were selected for this study of Th17 cell function. IL-17+CD4+ Th17 cells and CD127 expression on Th17 cells were determined by flow cytometry. Cytokine level was measured by ELISA. Peripheral and tissue-infiltrating CD4+ T cells were isolated using magnetic beads, and then stimulated with IL-7 and/or signal transducer and activator of transcription 5 inhibitor. Activated signaling molecules were analyzed by flow cytometry. Peripheral and tumor-infiltrating Th17 cells percentage was decreased, while peripheral IL-7 level was also reduced in melanoma patients. There was no significant difference of CD127 expression on Th17 cells between melanoma patients and controls. Antiapoptotic protein Bcl-2 was downregulated, whereas proapoptotic protein-activated caspase-3 was upregulated in peripheral and tissue-infiltrating Th17 cells in melanoma patients. Higher concentration of IL-7 (10 ng/mL), but not lower IL-7 concentration (1 ng/mL), promoted Bcl-2 expression and decreased caspase-3 expression in Th17 cells in melanoma patients. Inhibition of signal transducer and activator of transcription 5 resulted in the downregulation of Bcl-2 while upregulation of caspase-3 in Th17 cells. The present data suggested that reduced IL-7 responsiveness might be insufficient for Th17 activation in patients with primary cutaneous melanoma.

Effect of lycopene on titanium implant osseointegration in ovariectomized rats.

BACKGROUND: Lycopene prevents bone loss in osteopenic models. However, the role of lycopene in the success rate of dental implants under osteopenic conditions remains unknown. The aim of this study was to evaluate whether lycopene prevents delayed implant osseointegration in an ovariectomized (OVX) rat model. METHODS: Thirty female Sprague-Dawley rats were randomly divided into the following groups: OVX with vehicle (OVX group), OVX with lycopene (OVX + lycopene group) and sham-operated with vehicle (sham group). Twelve weeks after ovariectomy or sham operation, titanium implants were placed into the distal metaphysis of the bilateral femurs of each rat. These rats were subsequently gavaged with lycopene (50 mg/kg/day) or vehicle. After 12 weeks of gavage, all rats were sacrificed, and specimens were harvested. Sample osseointegration was evaluated by biomechanical testing, 3D micro-computed tomography (micro-CT) analysis and histomorphometric analysis. RESULTS: Compared with the OVX group, the OVX + lycopene group showed a 69.3% increase in the maximum push-out force (p < 0.01). Micro-CT data for the femurs in the OVX + lycopene group showed significantly higher bone volume, trabecular thickness and less trabecular space than did those in the OVX group. The bone area (BA) around the implant and bone contact (BC) with the implant were increased by 72.3% (p < 0.01) and 51.4% (p < 0.01) in the OVX + lycopene group, respectively, compared with those in the OVX group. There was no significant difference in the mechanical test, micro-CT scanning and histomorphometric data between the OVX + lycopene and sham groups (p > 0.05). CONCLUSIONS: Lycopene improved implant osseointegration, fixation and bone formation under osteopenic conditions, suggesting that lycopene is a promising therapeutic agent to prevent delayed implant osseointegration and bone loss under osteopenic conditions.