Causal associations between gut microbiota and cutaneous melanoma: a Mendelian randomization study.

Background: Cutaneous melanoma (CM) of the skin stands as the leading cause of mortality among skin cancer-related deaths. Despite the successes achieved with novel therapies such as immunotherapy and targeted therapy, their efficacy remains limited, necessitating further exploration of new treatment modalities. The gut microbiota and CM may be linked, as indicated by a growing body of preclinical and observational research. Nevertheless, the exact correlation between the intestinal microbiota and CM remains to be determined. Therefore, this study aims to assess the potential causal relationship between the gut microbiota and CM. Methods: The study utilized exposure data obtained from the MiBioGen consortium's microbiome GWAS, which included a total of 18,340 samples gathered from 24 population-based cohorts. Data at the summary level for CM were acquired from the UK Biobank investigation. The main analytical strategy utilized in this research was the inverse variance weighted (IVW) technique, supported by quality assurance measures like the weighted median model, MR-Egger, simple model, and weighted model approaches. The Cochran's Q test was used to evaluate heterogeneity. To ascertain potential pleiotropy, we employed both the MR-Egger regression and the MR-PRESSO test. Sensitivity analysis was conducted using the leave-one-out method. Results: The study found that the class Bacteroidia (OR = 0.997, 95% CI: 0.995-0.999, p = 0.027), genus Parabacteroides (OR = 0.997, 95% CI: 0.994-0.999, p = 0.037), order Bacteroidales (OR = 0.997, 95% CI: 0.995-0.999, p = 0.027), and genus Veillonella (OR = 0.998, 95% CI: 0.996-0.999, p = 0.046) have protective effects on CM. On the order hand, the genus Blautia (OR = 1.003, 95% CI: 1-1.006, p = 0.001) and phylum Cyanobacteria (OR = 1.002, 95% CI: 1-1.004, p = 0.04) are identified as risk factors for CM. Conclusion: We comprehensively assessed the potential causal relationship between the gut microbiota and CM and identified associations between six gut microbiota and CM. Among these, four gut microbiota were identified as protective factors for CM, while two gut microbiota were identified as risk factors for CM. This study effectively established a causal relationship between the gut microbiota and CM, thereby providing valuable insights into the mechanistic pathways through which the microbiota impacts the progression of CM.

Effective of a novel technique for sensitive skin treatment with optimal pulse technology: A clinical study.

BACKGROUND AND AIMS: Photomodulation is a non-photothermal effect that mobilizes energy and regulates cell activity at the mitochondrial level, and has been used to treat sensitive skin (SS) in recent years. Based on the photomodulated effect of optimal pulse technology (OPT), we developed a novel treatment mode (advanced OPT with low energy, three pulses, long pulse width, AOPT-LTL) for the treatment of facial SS and evaluated its effectiveness. METHODS: A total of thirty Chinese women with SS were included in this study. Patients were received different times of AOPT-LTL treatment with an interval of 2 to 4 weeks depending on the severity. Clinical improvement was evaluated by comparing baseline and post-treatment photographs. In addition, the skin objective signs and subjective symptoms, as well as adverse events and patient satisfaction were also analyzed and tabulated. RESULTS: All included patients completed the treatment and follow-up period. After one course of treatment, 76.7% of patients had a Symptom Score Reducing Index (SSRI) >20%, suggesting that the treatment was effective. Within two courses of treatment, all patients had SSRI >20%, demonstrating significant improvement in skin sensitivity. The analysis of clinical photographs showed that facial dryness, desquamation, flushing, and skin color significantly improved, capillary density decreased, the dilated capillaries were retracted. During the treatment period, no obvious adverse reactions occurred in any patients, and the patients' satisfaction was high. CONCLUSIONS: This novel technique of AOPT-LTL might be an effective and safe modality for the treatment of SS.

Novel technique for rosacea treatment using optimal pulse technology: In vivo and clinical studies.

BACKGROUND: Rosacea is a chronic inflammatory skin disease affecting the face, and the current treatment effect is not satisfactory. Based on the photomodulation of optimal pulse technology (OPT), we developed a novel treatment mode, namely, advanced OPT with low energy, three pulses, and long pulse width (AOPT-LTL). AIMS: We aimed to explore the feasibility and underlying molecular mechanisms of AOPT-LTL treatment in a rosacea-like mouse model. Furthermore, we evaluated the safety and efficacy in patients with erythematotelangiectatic rosacea (ETR). MATERIALS AND METHODS: Morphological, histological, and immunohistochemical analyses were used to investigate the efficacy and mechanisms of AOPT-LTL treatment in the LL-37-induced rosacea-like mouse model. Moreover, 23 patients with ETR were included and received different times of treatment at intervals of 2 weeks depending on the severity of their condition. The treatment effect was assessed by comparing clinical photographs at baseline, 1 week, and 3 months after treatment, combined with the red value, GFSS, and CEA scores. RESULTS: After the AOPT-LTL treatment of the mice, we observed that the rosacea-like phenotype, inflammatory cell infiltration, and vascular abnormalities were significantly ameliorated, and the expression of the core molecules of rosacea was significantly inhibited. In the clinical study, the AOPT-LTL treatment exerted satisfactory therapeutic effects on erythema and flushing of ETR patients. No serious adverse events were observed. CONCLUSIONS: AOPT-LTL is a safe and effective method for the treatment of ETR.

Second intention healing of nasal ala and dorsum defects in Asians.

BACKGROUND: Reconstruction of defects of nasal ala and dorsum after surgical excision presents a substantial challenge to dermatologic surgeons. Second intention healing is a simple and extremely useful method to optimize cosmesis after skin cancer removal. OBJECTIVES: This study reported the cosmetic outcomes after second intention healing of nasal ala and dorsum defects in Asians, and estimated the time to epithelialization and complete healing. MATERIALS AND METHODS: Fifteen defects (<1 cm in diameter) of the nasal ala and dorsum in 10 patients were allowed to heal by secondary intention. Cosmetic results were evaluated and the time to epithelialization and complete healing were recorded. RESULTS: Cosmetic outcomes were good to excellent in 80% of the defects; defects of the dorsum showed poorer cosmetic results than defects of the ala. The wounds needed 5-17 days (mean 11.3; SD ± 4.18) to complete epithelialization and 10-24 days (mean 17.7; SD ± 4.85) to heal completely. CONCLUSIONS: Second intention healing of small nasal ala and dorsum defects (<1 cm in diameter) in Asians produces satisfactory cosmetic results with a low complication rate.

Knockdown of fibronectin extra domain B suppresses TGF-ß1-mediated cell proliferation and collagen deposition in keloid fibroblasts via AKT/ERK signaling pathway.

Keloids represent a dermal fibrotic disease characterized by excess collagen deposition and invasion of normal skin beyond the wound boundary, similar to malignant tumor features. Fibronectin extra domain B (EDB) is highly expressed in many tumors but has not been studied in keloids. The present study aimed to investigate the expression and the influence of EDB on keloid and elucidate the putative signaling pathway. We examined expression of EDB and the effects of EDB on fibroblast proliferation, apoptosis and the expression of the related proteins and genes. The level of phosphorylation of Smad, ERK, and AKT was estimated to elucidate the signaling pathways. The results showed that EDB in human keloid tissues and fibroblasts was overexpressed. EDB knockdown suppressed the cell proliferation of keloid fibroblasts (KFs) treated by transforming growth factor-ß1 (TGF-ß1). Also, the phosphorylation of Smad, ERK, and AKT in TGF-ß1-induced KFs was inhibited In addition, the low expression of pro-collagen-I (Col-I) and Col-III protein and mRNA level was observed in the siEDB group. EDB knockdown inhibited cell proliferation and suppressed collagen deposition in TGF-1-induced KFs. The underlying mechanism is the activation of TGF-ß1/Smad, ERK, and AKT signaling pathways. Together, the results suggested that EDB is a promising therapeutic target for keloid clinical treatment.

A novel technique for treating atrophic facial scars in Asians using ultra-pulse CO2 laser.

BACKGROUND AND AIMS: Fractional lasers have become increasingly popular for treating atrophic scars, but their effectiveness is limited for deeper scars. We developed a novel technique (manual fractional thermal contraction technology, MFTCT) using an ultra-pulse CO2 laser and evaluated its efficacy and safety for treating atrophic facial scars. METHODS: A total of 44 patients with atrophic facial scars were treated with MFTCT every 8 weeks for 1-4 times. Overall scar improvement was assessed by photographs taken at baseline and 3 months after the last treatment according to the 4-point global assessment scale (GAS) and ECCA grading scale. Improvements in color, distortion, and texture were assessed by the modified Manchester Scar Scale and scored individually from 1 to 4. Pain degrees and adverse reactions during and after treatment were recorded. RESULTS: A total of 44 patients completed the treatment and follow-ups; of them, 89% reported at least 50% overall improvement after the last treatment. The mean ECCA scores fell from 67.50 ± 23.98 to 45.68 ± 18.57 (a 32% improvement), and the change was significant (P = .000). The average score for overall improvement was 3.48. The average scores for color, distortion, and texture were 3.07 ± 0.62, 3.27 ± 0.50, and 3.52 ± 0.51, respectively. Mean pain degree score was 4.27 ± 1.04, and mean erythema duration was 28.43 ± 6.58 days. Some patients developed pigmentation for a few months that resolved with topical treatment. CONCLUSION: Manual fractional thermal contraction technology has definite clinical efficacy in the treatment of atrophic facial scars with fewer adverse reactions and is worth using in the clinical setting.

Lipid nano-bubble combined with ultrasound for anti-keloids therapy.

Keloids were characterized by excessive growth of fibrous tissues, and shared several pathological characteristics with cancer. They did put physical and emotional stress on patients in that keloids could badly change appearance of patients. N-(4-hydroxyphenyl) retinamide (4HPR) showed cytotoxic activity on a wide variety of invasive-growth cells. Our work was aim to prepare N-(4-hydroxyphenyl) retinamide-loaded lipid microbubbles (4HPR-LM) combined with ultrasound for anti-keloid therapy. 4HPR-loaded liposomes (4HPR-L) were first prepared by film evaporation method, and then 4HPR-LM were manufactured by mixing 4HPR-L and perfluoropentane (PFP) with ultrasonic cavitation method. The mean particle size and entrapment efficiency 4HPR-LM were 113 nm and 95%, respectively. The anti-keloids activity of 4HPR-LM was assessed with BALB/c nude mice bearing subcutaneous xenograft keloids model. 4HPR-LM, combined with ultrasound, could significantly induce apoptosis of keloid fibroblasts in vitro and inhibited growth of keloids in vivo. Thus, 4HPR-LM could be considered as a promising agent for anti-keloids therapy.

Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis.

BACKGROUND: Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars. METHODS: Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis. RESULTS: Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions. CONCLUSION: There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to confirm our conclusion.