Porous tremella-like NiMoP/CoP network electrodes as an efficient electrocatalyst.

The design of efficient, stable and cost-effective electrocatalysts for the hydrogen evolution reaction holds substantial significance in water electrolysis, but it remains challenging. Tremella-like nickel-molybdenum bimetal phosphide encapsulated cobalt phosphide (NiMoP/CoP) with hierarchical architectures has been effectively synthesized on nickel foam (NF) via a straightforward hydrothermal followed by low-temperature phosphating method. Based on the unique structural benefits, it significantly increases the number of redox active centers, enhances the electrical conductivity of materials, and diminishes the ion diffusion path lengths, thereby promoting efficient electrolyte penetration and reducing the inherent resistance. The as-obtained NiMoP/CoP/NF electrocatalyst exhibited remarkable catalytic activity with an ultralow overpotential of 38 mV (10 mA cm-2) and low Tafel slope of 83 mV dec-1. The straightforward synthesis process and exceptional electrocatalytic properties of NiMoP/CoP/NF demonstrate great potential for the HER to replace the precious metal catalyst.

Cyclodextrin-conjugated low-molecular-weight polyethyleneimine as a macromolecular contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone via host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist (r1 = 4.25 mM-1 s-1) used in clinic, the PC/Ad-PEG2000-PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity (r1 = 11.62 mM-1 s-1) with excellent biocompatibility. Furthermore, in vivo experiments demonstrated that PC/Ad-PEG2000-PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility in vivo. Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.

Experience and caring needs of patients with psoriasis: A qualitative meta-synthesis.

BACKGROUND: As a chronic skin disease, psoriasis often affects the physical, psychological and social status of the patient, which in turn impacts on their experience of illness and needs. However, there is no review of qualitative research that integrates and analyses the experiences and needs of these three influences from a holistic perspective. METHODS: This review follows the ENTREQ guidelines. Six English databases (JBI, Cochrane Library, PubMed, PsyINFO, CINAHL and Embase) and three Chinese databases (CNKI, VIP and Wanfang) were searched from January 2012 to October 2022. Literature was included if it was relevant to the experience of illness and caring needs of patients with psoriasis. The JBI-QARI was used to rate the quality of included studies. RESULTS: Eleven studies were included in the meta-synthesis. Four analytical themes were identified for analysis: physical challenges, psychological discomfort, social phenomena and caring needs. CONCLUSIONS: The combined physical, psychological and social effects of psoriasis and the consequent caring needs should be emphasised. Health professionals, including doctors and nurses, should be aware of the multiple changes in patients and their coping strategies, provide information about psoriasis, monitor and follow-up regularly over time and obtain feedback to inform further treatment and care so as to develop high-quality therapeutic interventions to help and guide patients with their coping strategies. RELEVANCE TO CLINICAL PRACTICE: These findings describe the physical, psychological and social experiences of illness and caring needs of patients with psoriasis. Healthcare professionals should be more aware of patients' easily overlooked psychological and social distress, providing prompt attention and recognition of patients' experiences and needs, offering relevant assistance and support and enhancing daily, regular follow-up to help them improve their understanding of and ability to manage their illness. NO PATIENT OR PUBLIC CONTRIBUTION: This is a meta-synthesis without direct patient involvement.

Proinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy.

The success of macrophage-based adoptive cell therapy is largely constrained by poor polarization from alternatively activated (M2-like) to classically activated (M1-like) phenotype in the immunosuppressive tumor microenvironment (TME). Here, we show that the engineered macrophage (eMac) with a heat-inducible genetic switch can induce both self-polarization of adoptively transferred eMac and re-polarization of tumour-associated macrophages in response to mild temperature elevation in a mouse model. The locoregional production of proinflammatory cytokines by eMac in the TME dose not only induces the strong polarization of macrophages into a classically activated phenotype, but also ensures that the side effects typical for systemically administrate proinflammatory cytokines are avoided. We also present a wearable warming device which is adaptable for human patients and can be remotely controlled by a smartphone. In summary, our work represents a safe and efficient adoptive transfer immunotherapy method with potential for human translation.

Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases. METHODS: Serum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function. RESULTS: miR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells. CONCLUSIONS: Our findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells.

Correction: Intracellular regulation of zinc by metal-organic framework-mediated genome editing for prostate cancer therapy.

Correction for 'Intracellular regulation of zinc by metal-organic framework-mediated genome editing for prostate cancer therapy' by Yanan Xue et al., Biomater. Sci., 2023, https://doi.org/10.1039/d3bm00002h.

Optimal Irreversible Electroporation Combined with Nano-Enabled Immunomodulatory to Boost Systemic Antitumor Immunity.

In this work, we proposed nµPEF, a novel pulse configuration combining nanosecond and microsecond pulses (nµPEF), to enhance tumor ablation in irreversible electroporation (IRE) for oncological therapy. nµPEF demonstrated improved efficacy in inducing immunogenic cell death, positioning it as a potential candidate for next-generation ablative therapy. However, the immune response elicited by nµPEF alone was insufficient to effectively suppress distant tumors. To address this limitation, we developed PPR@CM-PD1, a genetically engineered nanovesicle. PPR@CM-PD1 employed a polyethylene glycol-polylactic acid-glycolic acid (PEG-PLGA) nanoparticle encapsulating the immune adjuvant imiquimod and coated with a genetically engineered cell membrane expressing programmed cell death protein 1 (PD1). This design allowed PPR@CM-PD1 to target both the innate immune system through toll-like receptor 7 (TLR7) agonism and the adaptive immune system through programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PDL1) checkpoint blockade. In turn, nµPEF facilitated intratumoral infiltration of PPR@CM-PD1 by modulating the tumor stroma. The combination of nµPEF and PPR@CM-PD1 generated a potent and systemic antitumor immune response, resulting in remarkable suppression of both nµPEF-treated and untreated distant tumors (abscopal effects). This interdisciplinary approach presents a promising perspective for oncotherapy and holds great potential for future clinical applications.

One-pot self-assembled bimetallic sulfide particle cluster-supported three-dimensional graphene aerogel as an efficient electrocatalyst for the oxygen evolution reaction.

The preparation of an electrocatalyst for the oxygen evolution reaction (OER) with high catalytic activity, good long-term durability and rapid reaction kinetics through interface engineering is of great significance. Herein, we have developed a bimetallic sulfide particle cluster-supported three-dimensional graphene aerogel (FeNiS@GA), which serves as an efficient electrocatalyst for OER, by a one-step hydrothermal method. Profiting from the synergy of the FeNiS particle cluster with high capacitance and GA with its three-dimensional porous nanostructure, FeNiS@GA shows a high specific surface area, large pore volume, low contact resistance, and decreases the electron and ion transport routes. FeNiS@GA exhibits outstanding OER activity (when the current density is 50 mA cm-2, the overpotential is 341 mV), low Tafel slope (63.87 mV dec-1) and remarkable stability in alkaline solutions, outperforming FeNiS, NiS@GA, FeS@GA and RuO2. Due to its simple synthesis process and excellent electrocatalytic performance, FeNiS@GA shows great potential to replace noble metal-based catalysts in practical applications.

Polysulfide induced synthesis of a MoS2 self-supporting electrode with wide-layer-spacing for efficient electrocatalytic water splitting.

Efficient non-noble metal bifunctional electrocatalysts can increase the conversion rate of electric energy in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Herein, a ball & sheet MoS2/Ni3S2 composite with wide-layer-spacing and high 1T-rich MoS2 is assembled on nickel foam (NF) via a two-step solvothermal method with polymeric sulfur (S-r-DIB) as the sulfur source. The obtained material serves as both the cathode and the anode toward overall water splitting in an alkaline electrolyte. The results proved that the interpenetration of MoS2/Ni3S2-p with a ball and sheet structure increased the material active surface area and exposed more catalytic active sites, which contributed to the penetration of solution and the transfer of charge/hydrion. Meanwhile, two different semiconductors of MoS2 and Ni3S2 along with the presence of ample active sulfur edge sites and few-layer, wide-layer-spacing structures of MoS2 lead to an outstanding electrocatalytic activity. In particular, the electrodes of MoS2/Ni3S2-p only need a battery voltage of 1.55 V at 10 mA cm-2. The bifunctional electrocatalyst MoS2/Ni3S2-p also shows excellent stability at large current densities during the electrochemical test.

Intracellular regulation of zinc by metal-organic framework-mediated genome editing for prostate cancer therapy.

Normal prostate tissues generally exhibit a higher level of zinc to maintain their special "citrate-producing" metabolism, while its level dramatically decreases during prostate tumorigenesis. Despite the significant antitumor effects, the intracellular accumulation of zinc in prostate cancer cells also promotes the expression of ZNT1, which in turn results in the efflux of zinc and attenuated cytotoxicity against cancer cells. To solve the dilemma, we developed a 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid (DUPA)-decorated zeolitic imidazolate framework-8 (ZIF8), which is able to load plasmid DNA encoding the Cas9 editor and single-guide RNA to form Cas9@ZIF8-DUPA nanocomplexes. The intracellular delivery of Cas9@ZIF8-DUPA simultaneously increases the level of zinc and inhibits the ZNT-1 function by disrupting the SLC30A1 gene to prevent the efflux of zinc in prostate cancer cells. Due to the high affinity between DUPA and the prostate-specific membrane antigen, Cas9@ZIF8-DUPA nanocomplexes exhibit excellent prostate tumor-targeting ability. The internalization and degradation of Cas9@ZIF8-DUPA not only release free zinc and Cas9 editors, but also reduce zinc efflux through Cas9-mediated genome editing that disables the function of ZNT1. As a result, Cas9@ZIF8-DUPA nanocomplexes exhibit significant antitumor activity and extended survival in the mouse model bearing prostate tumors. The current platform offers an alternative therapeutic strategy and holds tremendous translational potential as an anticancer nanomedicine for prostate cancer treatment.

The importance of temperature monitoring in predicting wound healing.

CONCLUSION: Upon wound formation, the wound temperature rises in the first 3-4 days until reaching its peak. It then falls at about one week after wound formation. In the second week after wound formation, the wound temperature decreases steadily to the baseline indicating a good wound condition and progression towards healing. While a continuous high temperature is often a sign of excessive inflammation or infection, which indicates urgent need of intervention and treatment.

Non-invasive activation of intratumoural gene editing for improved adoptive T-cell therapy in solid tumours.

Adoptive T-cell therapy against solid tumours is limited by the apoptosis resistance mechanisms of tumour cells and by the extracellular, immunosuppressive tumour microenvironment. Here we report a temperature-sensitive genome-editing nanodevice that can deliver a Cas9 editor with an external trigger which can be used to edit the genome of tumour cells to reduce resistance to apoptosis and modulate the tumour microenvironment via a mild heating trigger. After local or systemic delivery of Cas9, mild heating is induced by non-invasive near-infrared (NIR) light or focused ultrasound (FUS) to activate Cas9, which initiates simultaneous genome editing of HSP70 (HSPA1A) and BAG3 in tumour cells. This disrupts the apoptotic resistance machinery of the tumour cells against adoptive T cells. At the same time, an NIR- or FUS-induced mild thermal effect reshapes the extracellular tumour microenvironment by disrupting the physical barriers and immune suppression. This facilitates the infiltration of adoptive T cells and enhances their therapeutic activity. Mild thermal Cas9 delivery is demonstrated in different murine tumour models which mimic a range of clinical indications, including a tumour model based on humanized patient-derived xenografts. As a result, the non-invasive thermal delivery of Cas9 significantly enhances the therapeutic efficacies of tumour-infiltrating lymphocytes and chimeric antigen receptor T and shows potential for clinical application.

Remediation of soil contaminated with PAHs and γ-HCH using Fenton oxidation activated by carboxymethyl cellulose-modified iron oxide-biochar.

The remediation of soil contaminated with hydrophobic organic pollutants has attracted great public concern. In the present study, a novel catalyst using biochar supported ferro ferric oxide modified by carboxymethyl cellulose (CMC-Fe3O4/BC) was developed to activate the Fenton reaction for hazardous hydrophobic organic pollutants, and the degradation mechanisms were analyzed in terms of free radicals, electron transfer pathways and degradation intermediates. The results showed that the CMC-Fe3O4/BC-activated H2O2 system degraded nearly 100% of pyrene in the aqueous system after a 1440-min reaction. The catalyst was also applied to remediate industrial field soil contaminated with PAHs and γ-HCH. The removal rate of the total pollutants reached 61.1% after a 10-day reaction, which was higher than that of Fe3O4/BC without modification. CMC enabled the Fe3O4 particles to more equably distribute on the BC surface, further effectively activating H2O2 to generate more ⋅OH and forming different degradation products compared to the Fe3O4/BC. Additionally, the CMC-Fe3O4/BC-activated H2O2 system obviously enhanced electron transfer on the BC surface. Thus, the PAHs and γ-HCH could be degraded via electron transfer pathways.

Transcriptome Analysis Reveals the Profile of Long Non-Coding RNAs during Myogenic Differentiation in Goats.

The long non-coding RNAs (lncRNAs) are emerging as essential regulators of the growth and development of skeletal muscles. However, little is known about the expression profiles of lncRNAs during the proliferation and differentiation of skeletal muscle satellite cells (MuSCs) in goats. In this study, we investigate potential regulatory lncRNAs that govern muscle development by performing lncRNA expression profiling analysis during the proliferation (cultured in the growth medium, GM) and differentiation (cultured in the differentiation medium, DM1/DM5) of MuSCs. In total, 1001 lncRNAs were identified in MuSC samples, and 314 differentially expressed (DE) (FDR < 0.05, |log2FC| > 1) lncRNAs were screened by pairwise comparisons from three comparison groups (GM-vs-DM1, GM-vs-DM5, DM1-vs-DM5). Moreover, we identified the cis-, trans-, and antisense-regulatory target genes of DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these target genes were significantly enriched in muscle development-related GO terms and KEGG pathways. In addition, the network of interactions between DE lncRNAs and their target genes was identified, which included well-known myogenesis regulators such as Myogenic differentiation 1 (MyoD), Myogenin (MyoG), and Myosin heavy chain (MyHC). Meanwhile, competing endogenous RNA (ceRNA) network analysis showed that 237 DE lncRNAs could bind to 329 microRNAs (miRNAs), while miRNAs could target 564 mRNAs. Together, our results provide a genome-wide resource of lncRNAs that may contribute to myogenic differentiation in goats and lay the groundwork for future investigation into their functions during skeletal muscle development.

A phase Ia dose-escalation trial of Ametumumab (a fully human monoclonal antibody against epidermal growth factor receptor) in patients with advanced solid malignancies.

Background: Epidermal growth factor receptor (EGFR) is a well-known target for cancer treatment. However, the authorized anti-EGFR monoclonal antibodies generally cause several toxic effects, especially severe cutaneous toxicities as well as infusion reactions, and the clinical indications are limited. Here we developed Ametumumab, a fully human recombinant anti-EGFR monoclonal antibody. Objectives: To assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of Ametumumab. Design: A first-in-human phase Ia dose escalation study of Ametumumab in patients with advanced solid malignancies. Methods: An open-label, first-in-human dose escalation study was done in 22 patients with advanced malignancies who received six ascending dosages ranging from 75 to 750 mg/m2. Following a single dosage and a 28-day dose-limiting toxicity (DLT) monitoring period, patients were given repeated doses weekly. Blood samples were taken to determine the PK parameters of Ametumumab and anti-drug antibody concentrations. Every 8 weeks, radiographic tumor evaluations were conducted. Results: In this trial, no DLT was observed, and the maximum tolerated dose was not reached at doses up to 750 mg/m2. There were no severe adverse events but mild and moderate adverse effects, such as headache, proteinuria, and rash. Single-dose PK results demonstrated a straightforward linear relationship with dosage escalation. The medication concentrations accumulated and attained steady-state after four rounds of injections. It was calculated that 10 patients with disease control would be observed in the 22 evaluable patients. The disease control rate was 45.5%. Conclusion: The Ametumumab was well tolerated and safe in patients with advanced solid malignancies, exhibiting minimal immunogenicity, a long half-life, high levels of drug exposure in the blood, and preliminary effectiveness. Registration: The trial was registered with CTR20170343 on 10 April 2017, The China Center for Drug Evaluation.

Management of vaginal laxity through bilateral wall tightening without mucosal excision.

BACKGROUND: Vaginal tightening or vaginoplasty has been gaining popularity, while validated methods of evaluation and treatment are still lacking. Herein, we describe a bilateral wall tightening technique for vaginal laxity and evaluate the feasibility of this method. METHODS: From April 2020 to September 2021, 25 women with vaginal laxity underwent vaginal tightening, and 22 women were included in this retrospective observational study. The inclusion criteria were as follows: participants with at least one delivery and reported vaginal laxity, but without a history of underlying diseases. Vaginal pressure tests and questionnaires were used to evaluate vaginal laxity and sexual quality before and 6 months after the surgery. RESULTS: The study included 22 women (aged 29-46 years), and the follow-up period was 14.1 ± 3.3 months. The score based on the vaginal laxity questionnaire was improved as a result of surgery (preoperative median: 2.00, interquartile range [IQR]: 1.00-2.00; postoperative median: 5.00, IQR: 5.00-6.25, p < 0.001). The vaginal pressure increased from 2.3 ± 1.8 mm/Hg to 21.4 ± 3.7 mm/Hg. Sexual distress changed from 24.2 ± 8.9-16.1 ± 4.8 after surgery (p < 0.001), and sexual dysfunction with an average score of 20.1 ± 10.6 before surgery improved after the procedure (26.0 ± 10.8, p < 0.001). Women also reported improved scores in desire, arousal, orgasm, and satisfaction. In addition, there were no intraoperative complications or significant events during the follow-up period. CONCLUSIONS: Bilateral vaginal tightening without mucosal excision is a feasible and effective surgical approach for the management of vaginal laxity.

Hyaluronic acid-functionalized redox-responsive organosilica nanoparticles for targeted resveratrol delivery to attenuate acrylamide-induced toxicity.

The purpose of this study is to construct a redox-responsive and targeted nanoparticle to effectively deliver resveratrol (Res) for alleviating acrylamide (ACR) toxicity. Here, Res-loaded tetrasulfide-containing organosilica nanoparticles (DSMSNs) functionalized with hyaluronic acid on the surface (DSMSNs@Res@HA) were prepared. The DSMSNs@Res@HA nanoparticles were spherical with an encapsulation efficiency of 46.68 ± 1.64 % and a hydrated particle size of about 237.73 nm. As expected, DSMSNs@Res@HA were capable of significantly protecting PC12 cells against ACR-induced damage in oxidative stress, mitochondrial membrane potential decrease, and cell apoptosis compared with free Res and DSMSNs@Res at the equivalent dose. Moreover, DSMSNs@Res@HA could be biodegraded and released Res in response to GSH stimulus. In vivo experiments suggested that DSMSNs@Res@HA significantly reduced histological damage in the brain, liver, and kidney of rats compared with free Res and DSMSNs@Res. After oral administration of DSMSNs@Res@HA, the intestinal flora of ACR-treated rats could be effectively regulated by improving the species uniformity and abundance as well as recovering the species diversity. According to these findings, DSMSNs@Res@HA is worth further investigation as a potential therapeutic nanomedicine to alleviate ACR toxicity and restore gut microbiota diversity.

Unmanned Aerial Vehicle Mediated Drug Delivery for First Aid.

Timely administration of key medications toward patients with sudden diseases is critical to saving lives. However, slow transport of first-aid therapeutics and the potential absence of trained people for drug usage can lead to severe injuries or even death. Herein, an unmanned aerial vehicle (UAV)-mediated first-aid system for targeted delivery (uFAST) is developed. It allows unattended administration of emergency therapeutics-loaded transdermal microneedle (MN) patches toward patients to relieve symptoms by a contact-triggered microneedle applicator (CTMA). The implementability and safety of the uFAST for first aid is demonstrated in a severe hypoglycemic pig model by automatically delivering a glucagon patch with immediate and bioresponsive dual release modes. This platform technique may facilitate the development of UAV-mediated first-aid treatments for other sudden diseases.

Remediation of industrial site soil contaminated with PAHs using stage persulfate oxidation activated by Fe2+ chelated with sodium citrate.

The remediation for industrial site soil has attracted public concerns because of the hazardous and hydrophobic properties of organic pollutants existed in the soil. The persulfate oxidation activated by Fe2+ chelated with sodium citrate (PS/Fe2+/SC) was used to remediate different types of industrial site soils in the present study. The maximum removal rates of Σ16 PAHs in the Nanjing site soil (NJS) and Hefei site soil (HFS) were 73.6% and 85.8% after the second-stage oxidation, respectively. The late oxidation stages couldn't enhance the degradation efficiency of PAHs due to the increase of high crystalline Fe mineral phases both in the NJS and HFS, which significantly decreased the Fe2+/Fe3+ recycle and further inhibited the reactive oxygen species production during the remediation. The remediation using PS/Fe2+/SC could change the soil physicochemical properties, such as the functional groups, specific surface area (SSA), total pore volume (TPV) and some UV spectral parameters of soil particles. Additionally, the oxidation of PS/Fe2+/SC also altered the composition of soil dissolve organic matters, especially the fulvic acid, which further affected the Fe2+ oxidation. The study mainly discloses the mechanism of limitation using persulfate oxidation activated by Fe materials at late oxidation stage.

A combination treatment of drug-laser-photon for melasma: A retrospective study of clinical cases.

BACKGROUND: Combinational therapy such as taking tranexamic acid while using laser treatment has been proved potential efficacy by many experiments. However, there is few research which contains large samples and consistent observations. OBJECTIVE: We evaluated clinical efficacy and safety of a new systemic treatment of drug-laser-photon therapy. METHODS: Retrospective and randomized investigator-blinded study of 75 patients with mixed type melasma was analyzed. At each visit, standardized photographs were taken using VISIA. Modified melasma area and severity index (mMASI) scores were marked using photographs by two dermatologists. RESULTS: The mMASI score decreased significantly from 6.92 to 3.84 after the treatment. The VISIA analyze right cheek data shows: Spots (from 49.67 ± 3.43 to 56.09 ± 3.31), UV spots (from 41.39 ± 24.45 to 44.56 ± 25.86), and Brown spots (from 23.97 ± 17.89 to 28.16 ± 21.28) are statistically increased (p = 0.035, p = 0.018, p = 0.07). All patients feel varying degrees of improvement, about 10.17% felt very much improved, 30.51% felt much improved (51%-75%), 45.76% felt moderately improved (26%-50%), and 13.56% felt little improved (1%-25%). LIMITATIONS: This study was no control group. CONCLUSION: The efficacy and safety profile of the combination of drug-laser-photon therapy systemic treatment in melasma patients has been proved. It has potential possibility to become a new, reliable, widely suitable therapy strategy.