Melanoma, which evolves from melanocytes, is the most malignant skin cancer and is highly fatal, although it only accounts for 4% of all skin cancers. Numerous studies have demonstrated that melanoma has a large tumor mutational burden, which means that melanoma has great potential to achieve immune evasion. Tumor-associated macrophages (TAMs) are an important component of both the immune system and tumor microenvironment. Several studies have demonstrated their double-edged sword effects on melanoma. The present review focuses on the role of TAMs in melanoma development, including regulation of proliferation, invasion, metastasis, angiogenesis and chemical resistance of melanoma. Furthermore, the existing mechanisms of action of the TAM-targeting treatments for melanoma are reviewed. More broadly, the weak points of existing research and the direction of future research are finally identified and described. Contents 1. Introduction 2. Overview of macrophages in the TME 3. Double-edged sword effect of TAMs in melanoma 4. TAM-targeting therapies in melanoma 5. Conclusion and future perspectives

Purpose Caizhixuan hair tonic (CZX) is a topical traditional Chinese medicine (TCM) preparation for the treatment of androgenetic alopecia (AGA). However, its active compounds and underlying mechanism for treating AGA are still unclear. The purpose of this study was to observe the effects of CZX on hair growth promotion in AGA mice and to explore the active components and mechanism. Methods Testosterone propionate was administered subcutaneously to mice to establish an AGA mouse model. The therapeutic effects of CZX on AGA were evaluated by observing skin colour changes, hair growth time, and average hair length; calculating the hair growth score; and performing skin histopathological analysis. Following that, CZX chemical components were analysed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC–Q–TOF/MS). Network pharmacology was used to predict the major effects and possible mechanisms of CZX for the treatment of AGA. Furthermore, RT-qPCR and Western blotting were performed to assess the expression of key genes and proteins involved in PI3K/Akt and apoptosis pathways in order to validate CZX’s predicted mechanism in AGA. Results CZX promoted hair growth and improved the pathological morphology of hair follicles in the skin. In UPLC–Q–TOF/MS analysis, 69 components from CZX were isolated. Based on network pharmacology, CZX alleviated AGA by regulating PI3K/Akt and apoptosis pathways. According to RT-qPCR and Western blotting, CZX upregulated the expressions of PI3K, Akt, and Bcl-2, while downregulating that of Bax and caspase-3. Conclusions CZX promotes hair growth to treat AGA by regulating the PI3K/Akt and apoptosis pathways.