Objective To explore the key molecule and signaling pathway involved in the recruitment of cancer-associated fibroblasts (CAFs) by BRAF inhibitor (BRAFi)-resistant melanoma. Methods Tumor tissue sections were collected from 20 melanoma patients who received BRAFi-targeted therapy in Zhongshan Hospital, Fudan University, between September 2024 and September 2025, including 10 cases in the BRAFi-resistant group and 10 cases in the BRAFi-sensitive group. Immunohistochemical staining was performed to compare the number of CAFs in tumor tissues in the two groups. A co-culture model was established to compare the half-maximal inhibitory concentration (IC₅₀) of BRAFi in melanoma cells under co-culture conditions with CAFs versus non-co-culture conditions. Differential gene expression between BRAFi-sensitive and BRAFi-resistant melanoma was analyzed using publicly available sequencing data (GSE196434), and key differentially expressed genes were identified. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were employed to validate the expression differences of CXCL1 between BRAFi-sensitive and BRAFi-resistant melanoma cells, and to detect CXCL1 expression in melanoma cells treated or untreated with the AKT inhibitor (AKTi). Transwell invasion assays were performed to evaluate the recruitment capability of BRAFi-resistant and BRAFi-sensitive melanoma cells toward CAFs, and to compare the differences in recruitment capability of melanoma cells toward CAFs among the AKTi-treated group, the AKTi＋CXCL1-treated group, and the control group. Results The number of CAFs was significantly higher in the BRAFi-resistant group than that in the BRAFi-sensitive group (P＜0.01). The cell viability (P＜0.01) and IC₅₀ were higher in the melanoma co-culture group with CAFs than in the non-co-culture group. CXCL1 was identified as a key differentially expressed gene, with higher expression in BRAFi-resistant melanoma than in BRAFi-sensitive melanoma (P＜0.01). AKTi treatment suppressed CXCL1 expression in BRAFi-resistant melanoma (P＜0.01). BRAFi-resistant melanoma exhibited a stronger CAF-recruiting capacity than BRAFi-sensitive melanoma (P＜0.05), and AKTi treatment reduced its ability to recruit CAFs (P＜0.05). This effect was restored after the addition of exogenous CXCL1 (P＜0.05). Conclusions BRAFi-resistant melanoma activates the AKT pathway to upregulate CXCL1, thereby recruiting CAFs.

The theoretical basis of premature aging originates from The Yellow Emperor's Inner Classic. The etiology of premature aging is complex， and the disease mechanism is based on deficiency. The treatment for premature aging is based on tonicity. The essence-Qi-spirit theory of Qiluo doctrine summarizes that "essence is the origin of life， Qi is the driving force of life， and spirit is the embodiment of life"， which is the law of life. The theory puts forward the core disease mechanism of aging， which states that "deficiency of kidney essence is the root of aging， deficiency of primordial Qi is the key to aging， impairment of soma and spirit is the manifestation of aging". The theory also proposes the treatment of "tonifying kidney and supplementing essence， harmonizing Yin and Yang， warming and supporting primordial Qi， and nourishing soma and spirit" and the representative anti-aging drugs. The article unfolds from the perspective of the concepts of natural life span， premature senility before fifty， decline， and aging and also explains the origins and connotations of premature aging. The article explains the disease mechanism of premature aging under the guidance of the essence-Qi-spirit theory of Qiluo doctrine， which is "early deprivation of kidney essence， deficiency of primordial Qi， accumulation of deficiencies into impairment， and decline and impairment of soma and spirit"， summarizes the progress of modern medical research on the treatment of premature aging and representative drugs， and finds that Bazi Bushen capsules have a precise therapeutic effect on the overall premature aging， systematic functional decline， and related diseases. The study provides theoretical basis and new ideas to solve the problems of premature aging and geriatric diseases.

Melanoma is the most malignant skin tumor, which is characterized by early metastasis and poor prognosis. In recent years, adoptive immunotherapy, as a new immunotherapy, has made great breakthrough in treatment of solid tumors. Represented by tumor-infiltrating lymphocyte, adoptive immunotherapy exhibits remarkable effects in melanoma. Its combination with immunotherapy or targeted therapy will be a certain trend for future development, while the large-scale clinical study on adoptive immunotherapy remains to be carried out. This article reviews the research progress of adoptive immunotherapy on melanoma.

Melanoma is a common and highly malignant tumor with rapid development, poor prognosis and high mortality in the field of plastic surgery. The incidence rate around the world is increasing year by year and the mortality rate ranks first among skin and soft tissue tumors. The rapid development of targeted and immunotherapeutic drugs has greatly improved the prognosis of patients with advanced melanoma. Currently, the improvement of curative effect brought by monotherapy with mainstream targeted drugs is still limited, and the overall remission rate is about 20%. A large number of clinical trials of non first-line and potential targeted drugs have been carried out, showing the value of these drugs and potential targets to clinicians. This article mainly reviews the potential targets and clinical trials of melanoma, in order to help clinicians better understand the prospect of targeted treatments of the disease and find more effective therapeutic drugs.

Melanoma is the skin malignancy with high potential of metastasis, and its morbidity rate is increasing every year. Melanoma patients exhibit a significantly elevated tumor mutational burden, with a higher prevalence of neoantigenic epitopes, leading to widespread activation of immune cells. Consequently, melanoma demonstrates a favorable response rate to immunotherapy. In this study, the infiltration landscape of common immune cells and their function in the melanoma microenvironment were depicted and analyzed. This study contributes to a better understanding among clinical practitioners of the role of the immune system in the development and progression of melanoma, and provides valuable guidance for the development of novel immunotherapeutic agents.

Melanoma is the most malignant skin tumor, which is characterized by early metastasis and poor prognosis. In recent years, adoptive immunotherapy, as a new immunotherapy, has made great breakthrough in treatment of solid tumors. Represented by tumor-infiltrating lymphocyte, adoptive immunotherapy exhibits remarkable effects in melanoma. Its combination with immunotherapy or targeted therapy will be a certain trend for future development, while the large-scale clinical study on adoptive immunotherapy remains to be carried out. This article reviews the research progress of adoptive immunotherapy on melanoma.

Melanoma is a common and highly malignant tumor with rapid development, poor prognosis and high mortality in the field of plastic surgery. The incidence rate around the world is increasing year by year and the mortality rate ranks first among skin and soft tissue tumors. The rapid development of targeted and immunotherapeutic drugs has greatly improved the prognosis of patients with advanced melanoma. Currently, the improvement of curative effect brought by monotherapy with mainstream targeted drugs is still limited, and the overall remission rate is about 20%. A large number of clinical trials of non first-line and potential targeted drugs have been carried out, showing the value of these drugs and potential targets to clinicians. This article mainly reviews the potential targets and clinical trials of melanoma, in order to help clinicians better understand the prospect of targeted treatments of the disease and find more effective therapeutic drugs.

Melanoma is the skin malignancy with high potential of metastasis, and its morbidity rate is increasing every year. Melanoma patients exhibit a significantly elevated tumor mutational burden, with a higher prevalence of neoantigenic epitopes, leading to widespread activation of immune cells. Consequently, melanoma demonstrates a favorable response rate to immunotherapy. In this study, the infiltration landscape of common immune cells and their function in the melanoma microenvironment were depicted and analyzed. This study contributes to a better understanding among clinical practitioners of the role of the immune system in the development and progression of melanoma, and provides valuable guidance for the development of novel immunotherapeutic agents.

Humans ; Intracranial Hemorrhage, Hypertensive ; East Asian People ; Hypertension ; Cerebral Hemorrhage

Objective:To study the expression level of CD73 in cutaneous melanoma and its clinical significance, and to explore its role and molecular mechanism in the occurrence and development of melanoma.Methods:Expression level of the gene NT5E in melanoma was analyzed according to RNA sequencing data from the CCLE database. CD73 expression level was tested in 145 melanoma tissues and corresponding para-tumor tissues by immunohistochemistry tissue microarray. The samples came from 78 male and 67 female patients who received surgical resection and were pathologically diagnosed as melanoma in the department of plastic surgery in Zhongshan Hospital from January of 2008 to December of 2017. The relationship between CD73 expression level and clinicopathological features as well as prognosis was analyzed. Melanoma cell line was transfected with CD73 gene overexpression lentivirus and negative control vectors, respectively. The transfection efficiency was verified by qRT-PCR and Western blot. CCK-8, wound healing and Transwell assays were used to evaluate the proliferation, migration and invasion abilities of the overexpression group and control group. Subcutaneous xenograft tumor models were established in nude mice to assess the tumorigenicity of the two groups. Transcriptome sequencing, GO and KEGG analyses were performed. The expression levels of pAKT and pGSK3β were detected by Western blot. The measurement data were expressed as Mean ±SD. Independent sample t-test was used for comparison between the two groups, and One-way ANOVA was employed for multi-group comparisons. The chi-square test was used for the categorical variables. P<0.05 was considered as statistically significant difference. Results:The expression of CD73 in melanoma was higher than that in para-tumor tissues ( P< 0.05). Higher expression level of CD73 was associated with higher Clark grade ( P= 0.014) and clinical stage ( P= 0.040). The overall survival and disease-free survival of patients with high-CD73-expression were significantly lower than those of patients with low-CD73-expression. CD73 expression, Clark grade and clinical stage are independent risk factors for the poor prognosis of patients with melanoma. Overexpression of CD73 significantly enhanced the proliferation, migration and invasion of melanoma cells in vitro and the tumorigenicity in vivo( P< 0.05). Transcriptome sequencing showed that CD73 was involved in several tumor related signaling pathways, among which the expression of pAKT and pGSK3β was elevated( P< 0.05). Conclusions:CD73 promotes the proliferation, migration and invasion of melanoma cells in vitro and the tumorigenicity in vivo through activating AKT signaling. CD73 is expected to become a new prognostic biomarker and therapeutic target for melanoma.