This brief report discusses the challenges in treating dermal melanosis and the limitations of current laser treatments due to inadequate tissue penetration and potential side effects. It introduces laser-induced optical breakdown (LIOB) as a novel therapeutic approach using a picosecond laser with a diffractive lens array (DLA) to target dermal pigmentation effectively. LIOB induces multiphoton ionization, leading to melanin clearance through phagocytosis and apoptotic cell removal, while also promoting dermal remodeling and collagen synthesis. We present a case of successful treatment of dermal pigmentation in a 55-year-old woman using 755 nm-picosecond alexandrite laser therapy, demonstrating significant improvement without recurrence. The findings suggest that LIOB offers a promising solution for acquired dermal hypermelanosis by addressing both diffuse and localized pigmentation effectively, leading to skin rejuvenation with minimal downtime and high patient satisfaction.

Melasma, a prevalent pigmentary disorder, is characterized by its complex etiology, propensity for recurrence, and resistance to treatment. However, there is currently no research on melasma through bibliometrics and visualisation. This study analyses the hotspots and trends in the field based on 2,709 publications from the Web of Science Core Collection (WOSCC). We carried out bibliometric analyses using Citespace software for different countries/regions, institutions, authors, and keywords. References were also analysed using VoSviewer. The results indicate that overall, there has been an increase in publications related to melasma since 2014. According to the analysis of the collaborative network diagram, the United States, Egyptian Knowledge Bank, and Benjakul Soottawat are the most contributing countries, institutions, and authors, respectively. Reference and keyword analyses have identified the pathogenesis and treatment of melasma as a prevalent topic in recent years. And how to find new treatment options and more effective therapeutic drugs is a future research trend. This is the first bibliometric and visual analysis of melasma-related literature to explore research hotspots and trends.

Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.

BACKGROUND: San-Bai Decoction (SBD) is a classic whitening prescription originally recorded in the \'Introduction to Medicine\' of the Ming Dynasty. SBD has been known for invigorating Qi and blood, promoting spleen and stomach, whitening skin, and fading melasma. However, its pharmacodynamic material basis and specific mechanism remain unclear.
OBJECTIVE: The aim of this study is to clarify the pharmacodynamic material basis of SBD and its mechanism of removing melasma.
METHODS: The positive and negative ion mass spectrum data of SBD extract were collected by UHPLC-Q-Exactive Orbitrap MS/MS, imported into Compound Discoverer (CD) 3.1 software, matched through the online database, and manually checked. Finally, the in vitro chemical components of SBD were classified. Similarly, the mass spectrum data of SBD in the serum of normal rats and melasma model rats were also analyzed by CD 3.1 software. The in vitro identified Compound file of SBD was imported into the Expected Compounds and the Generate Expected Compounds project was selected. The SBD compounds were then chosen under the Compound Section. All phase I and II reaction types related to SBD components were selected, and the metabolic platform of CD 3.1 software was utilized to process the results and obtain possible metabolites. The metabolites were scored and products with high scores were subsequently screened. According to literature comparison, the final metabolites of SBD in both normal rats and melasma model rats were determined and comprehensively analyzed. The Melasma model rats were constructed through intramuscular injection of progesterone and ultraviolet radiation B (UVB) irradiation. The preventing and treating effect of SBD on melasma were evaluated by regulating inflammation, epidermal collagen content, and oxidative stress. Additionally, the effect of SBD on the Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt)/Glycogen synthase kinase 3β (GSK3β) pathway was investigated through Western blot (WB) to explore its underlying mechanism on whitening and removing melasma efficacy.
RESULTS: Ultimately, 94 components were identified in SBD, including 41 flavonoids, 27 organic acids, and 9 glycosides, 3 terpenoids, 2 amides, 2 aldehydes, 1 phenylpropanoid and 9 other compounds. In the blood of normal rat group, a total of 24 prototype components and 61 metabolites were identified. Similarly, there were19 prototype components and 44 metabolites identified from the blood of melasma model rats. Pharmacodynamic experiment results indicated that SBD effectively reduced the incidence of melasma, prevent the loss of epidermal collagen, and elevate the activity of superoxide dismutase and decrease the malondialdehyde content in both liver and skin. Interestingly, the WB results demonstrated that SBD effectively activated PI3K/Akt/GSK3β pathway, and down-regulated the expression of melanin-related proteins.
CONCLUSIONS: For the first time, the components of SBD extracts, and its prototype components and metabolites in the blood of normal rats and melasma model rats were successfully identified by high-resolution liquid chromatography-mass spectrometry with CD software. Additionally, the differences of in vivo components of SBD between normal rats and melasma model rats were analyzed. The preventive and therapeutic effect of SBD on melasma was verified in the melasma model rats induced by progesterone and UVB irradiation, and its mechanism was related to activating PI3K/Akt/GSK3β pathway and downregulating the expression of melanin-related proteins. These results provide an experimental foundation for further research on the pharmacodynamic substance basis and pharmacodynamic mechanism of SBD, as well as developing new anti-melasma formula with SBD.

Melasma is a common condition of hyperpigmented facial skin. Picosecond lasers are reported to be effective for the treatment of melasma. We aimed to identify the most effective therapeutic mode and elucidate the potential molecular mechanisms of picosecond lasers for the treatment of melasma. Female Kunming mice with melasma-like conditions were treated using four different picosecond laser modes. Concurrently, in vitro experiments were conducted to assess changes in melanin and autophagy in mouse melanoma B16-F10 cells treated with these laser modes. Changes in melanin in mouse skin were detected via Fontana-Masson staining, and melanin particles were evaluated in B16-F10 cells. Real-time polymerase chain reaction and western blotting were used to analyse the expression levels of melanosome and autophagy-related messenger ribonucleic acid (mRNA) and proteins. A combination of large-spot low-fluence 1064-nm and fractional 1064-nm picosecond lasers resulted insignificant decreases in melanin as well as in mRNA and protein expression of melanin-synthesizing enzymes (TYR, TRP-1 and MITF). This combination also led to increased expression of the autophagy-related proteins, Beclin1 and ATG5, with a marked decrease in p62 expression. Intervention with the PI3K activator, 740 Y-P, increased TYR, TRP-1, MITF, p-PI3K, p-AKT, p-mTOR and p62 expression but decreased the expression of LC3, ATG5 and Beclin1. A combination of large-spot low-fluence 1064-nm and fractional 1064-nm picosecond lasers proved more effective and safer. It inhibits melanin production, downregulates the PI3K/AKT/mTOR pathway, enhances melanocyte autophagy and accelerates melanin metabolism, thereby reducing melanin content.

BACKGROUND: Skin barrier alterations play a crucial function in melasma development. Past researches have demonstrated variations in lipid content between the epidermis of melasma lesions and normal tissues, along with the varied expression of lipid-related genes in melasma. This study aimed to analyze the lipidome profiles of skin surface lipids (SSL) in patients with melasma before and after treatment to understand associated abnormalities.
METHODS: Melasma was treated with tranexamic acid orally and hydroquinone cream topically. Disease was assessed using the Melasma Area and Severity Index (MASI), and the impact to life was evaluated with Melasma Quality of Life (MELASQoL) score. Epidermal melanin particles were observed using reflection confocal microscopy (RCM), whereas epidermal pigment and blood vessel morphology were observed using dermoscopy, and SSL samples were collected. Specific information regarding alterations in lipid composition was obtained through multivariate analysis of the liquid chromatography-mass spectrometry data.
RESULTS: After treatment, patients with melasma exhibited decreased MASI and MELASQoL scores (P < 0.001); RCM revealed reduced melanin content in the lesions, and dermoscopy revealed fewer blood vessels. Fifteen lipid subclasses and 382 lipid molecules were identified using lipidomic assays. The expression levels of total lipids, phosphatidylcholine, and phosphatidylethanolamine in the melasma lesions decreased after treatment (P < 0.05).
CONCLUSIONS: This study revealed alterations in the SSL composition after effective melasma treatment, suggesting a compensatory role for lipids in melasma barrier function. The mechanism involving SSL and the lipid barrier, which influences melasma\'s occurrence, needs further elucidation.

Melasma is an acquired hypermelanotic condition characterized by the presence of irregular light-to-dark brown macules that primarily manifest on the sun-exposed areas of the skin, particularly the face. The management of melasma poses significant challenges, as it is often recalcitrant to treatment and tends to recur despite successful treatment. In this study, we explored a safe, easy, and effective melasma treatment strategy. A hyaluronic acid (HA)-based microneedle (MN) patch loaded with tranexamic acid (TXA) was designed to deliver the necessary medication for melasma treatment. The MN patch features uniform needles with adequate mechanical strength and effective penetration and solubility in the skin without cytotoxicity. Remarkably, these MNs substantially reduce the thickness of the epidermis of melasma mice, curtail melanin production, and diminish dopachrome tautomerase (DCT) expression.

Although patients with refractory melasma have been treated using various methods, there is still no precise definition or summary of the therapies. To define refractory melasma and conduct a review of the treatments, we searched for relevant publications in PubMed, Web of Science, and the Cochrane Library, and a total of 35 references were obtained. Refractory melasma can be roughly defined as an ineffective treatment for melasma, including topical bleaching agents, chemical peels, laser therapy, microdermabrasion for more than six months, or chemical peels treated more than six times. Meanwhile, physicians should be careful when treating patients with darker skin and dermal or mixed types of melasma since these individuals do not respond well to treatment. Lasers combined with other methods, especially different types of lasers or topical agents, are considered more effective than monotherapy. Oral tranexamic acid (TXA) is a prospective cure for refractory melasma. Other methods include a combination of chemical peels, microneedling, or injections with additional therapies. In conclusion, we were able to provide a rough definition of refractory melasma and list the available therapies. According to the literature, the most prevalent treatment is laser combination therapy. However, laser treatment should be considered only after topical agents and chemical peeling have failed. Considering its side effects, efficacy, and safety, oral TXA may be a better option, but more research is needed to make a firm conclusion. Moreover, maintenance therapy is required after treatment.

OBJECTIVE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients.
METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient\'s satisfaction assessments (PSA).
RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period.
CONCLUSIONS: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.