OBJECTIVE:To explore the mechanism of Wenshen Zhuanggu Fang (, WSZG) against breast cancer bone metastasis from the perspective of macrophage polarization through bioinformatics and experiments. METHODS:Bioinformatics study was used to explore the mechanism underlying the effect of WSZG on breast cancer bone metastasis. Cell viability, migration, invasion and apoptosis assays were performed to detect the influence of WSZG on breast cancer cell MDA-MB-231BO promoted by macrophages. The protein expression level and cytokine content were detected by western blot and enzyme-linked immunosorbent assay kit in vitro. Tumor growth in vivo were performed to evaluate the effects of WSZG on breast cancer bone metastasis. M2/M1 ratio and the maker protein expression were detected by flow cytometry analysis, immun-ohistochemistry and immunofluorescence double staining. RESULTS:M2 macrophages associated with poor prognosis and may lead to secondary bone metastasis in patients with triple-negative breast cancer. WSZG could treat breast cancer bone metastasis through regulating macrophage polarization by signal transducers and transcription signaling activators (STAT) signaling pathway. WSZG downregulated STAT6, CD206 and Arginase-1, while upregulated STAT1 and Inducible Nitric Oxide Synthase, thus inhibited the M2 macrophage-promoted invasion and migration capabilities of MDA-MB-231BO cells. WSZG treatment suppressed the bone metastasis of breast cancer, and the M2/M1 ratio was reduced by regulating STAT expression in bone metastatic tissue. CONCLUSION:WSZG inhibited breast cancer bone metastasis by adjusting the promoting effect of macrophages on MDA-MB-231BO breast cancer cells and decreasing M2 polarization by downregulating STAT signaling.

AIMS:Breast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC). OBJECTIVES:To analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC. MATERIALS AND METHODS:Network pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC. RESULTS:According to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels. CONCLUSION:The study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.

The pathogenesis of psoriasis involves hyperproliferation of epidermal keratinocytes and abnormal interactions between activated keratinocytes and infiltrating immune cells. Emerging evidence has shown that keratinocytes play essential roles in both the initiation and maintenance of psoriasis, suggesting that exposing keratinocytes to agents with antiproliferative and anti-inflammatory effects may be effective for psoriasis treatment. Guggulsterone (GS), a plant sterol derived from the gum resin of Commiphora wightii, possesses a variety of pharmacological activities. However, the effects of GS on psoriasis and the underlying mechanism have not been elucidated. In this study, we evaluated the therapeutic effect of GS on psoriasis using an imiquimod-induced psoriasis mouse model and investigated the effect of GS on human keratinocytes and the underlying mechanism. We found that GS effectively alleviated psoriasis-like skin lesions in imiquimod-induced psoriasis model mice and that GS suppressed the proliferation, migration, and production of proinflammatory cytokines, chemokines and antimicrobial peptides in keratinocytes. Transcriptome analysis by RNA-seq revealed that the differentially expressed genes (DEGs) induced by GS in keratinocytes were intricately linked to the pathogenesis of psoriasis. Furthermore, STAT3, a key player in the development and pathogenesis of psoriasis, was identified as a critical downstream mediator of GS in keratinocytes. Mechanistically, GS upregulated the expression of miR-17-5p, which directly binds to the 3'-untranslated regions (3'UTRs) of JAK1 and STAT3, leading to the downregulation of JAK1 and STAT3 expression. Collectively, these findings suggest that GS may serve as an effective natural compound for the treatment of psoriasis.

In accordance with the Guiding Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovation of Traditional Chinese Medicine(TCM),the China Association of Chinese Medicine(CACM)organized multidisciplinary symposia on TCM-dominant diseases with the aim of advancing research on clinically dominant diseases in TCM,supporting specialty development,cultivating clinical talent,developing strategic plans for national science,and fostering academic innovation.The 42nd Academic Salon on Clinically Dominant Diseases,which was convened in Shanghai on 24 November 2024,brought together TCM experts,Western medicine experts,and interdisciplinary researchers for in-depth discussions on the current status,strengths,and limitations of and strategies to improve the integrated diagnosis and treatment of plasma cell mastitis(PCM).While consensus had been reached on recommendations for TCM and integrated approaches,detailed research pathways remain to be developed.In this work,we systematically examine the pathogenesis of and clinical management challenges related to PCM.Building on the therapeutic strengths of TCM,we propose 5 prioritized research domains with corresponding scientific planning:(1)Early identification and intervention strategies for PCM;(2)Optimization of TCM syndrome differentiation systems for PCM;(3)Standardization of efficient evaluation metrics for PCM therapies;(4)Mechanistic studies on the pathogenesis of PCM and TCM therapeutic targets;(5)Prevention protocols and complication management frameworks for PCM.We further delineate recommended research directions,anticipated outcomes,value propositions,and funding priorities.The aim of this research model,which was derived from the PCM-focused academic salon series,is to advance the development of high-quality TCM practices by informing national scientific planning,innovative drug development,research priorities,and the formulation of clinical guidelines.

Breast cancer (BC), a highly heterogeneous disease, has demonstrated a gradual increase in both incidence and mortality rates. At present, it has become one of the most common malignant tumors and the main cause of cancer death worldwide. While early screening is recognized as an effective preventive and therapeutic measure for BC, the disease continues to exhibit a high rate of metastasis. Metastatic BC is still the main cause of poor prognosis and death of patients, necessitating urgent investigation and resolution. Among the various metastatic sites of BC, bone metastases warrant particular attention due to their prevalence. In numerous studies on BC bone metastasis mechanisms, cancer markers have been shown to significantly influence the pattern and extent of BC metastasis and dissemination. In the tumor microenvironment, Ras-proximate-1 (RAP1), a GTPase protein, is not only upregulated in various malignant tumors and bone-related diseases, including BC, but also regulates migration, invasion, distant metastasis, and other signaling pathways in numerous malignant tumor cells, including BC as well. Despite these findings, there remains a paucity of advanced research and discussion on the relationship between RAP1 and BC bone metastasis. Furthermore, no clinically approved RAP1-related inhibitors for BC bone metastasis are currently available. Nevertheless, RAP1 and its associated signaling molecules represent potential molecular targets for the prevention and treatment of BC bone metastasis, warranting further investigation. Therefore, this article provides a comprehensive review of RAP1's pathogenic role in BC bone metastasis, emphasizes RAP1 and its associated signaling pathways, and summarizes current research on natural compounds and extracts that modulate BC bone metastasis via RAP1 or RAP1-related signaling pathways. This review aims to offer novel perspectives for developing RAP1 as a potential molecular target in the prevention and treatment of BC bone metastasis, as well as for the development of related therapeutic agents.

Granulomatous lobular mastitis (GLM) is a rare inflammatory breast disease, and there are few reports of GLM in pregnancy (GLMIP). Therefore, this study retrospectively analyzed cases diagnosed with GLMIP from 2011 to 2023 and found that in patients with GLMIP there were varied demographic manifestations such as age, pregnancy weeks, and numbers of pregnancy and delivery, and several associated complications including erythema nodosum, arthritis and lower extremity edema. Among them, 82.8% of the patients received integrated traditional Chinese medicine (TCM) and western medicine treatment, and 17.2% of the patients received TCM treatment alone, but the application rate of TCM treatment was 100%. The results showed that both groups significantly improved the effective rate (91.7% and 60.0%, respectively), improved breast appearance (4.1% and 20.0%, respectively), reduced the rate of progression or recurrence rate (8.3% and 60.0%, respectively), and shortened the time for complete remission (13.793 months vs 12.625 months, respectively). To date this study is the one with the largest sample size of GLMIP, but also the one with the largest sample size in which the combination of TCM treatment and non-surgical treatment was applied. The complications include erythema nodosum, arthritis and lower extremity edema. Therefore, the application of TCM in the treatment of GLMIP is worth promoting vigorously.

Breast cancer (BC) is an important cause of cancer-related death in the world. As a subtype of BC with the worst prognosis, triple-negative breast cancer (TNBC) is a serious threat to human life and health. In recent years, there has been an increasing amount of research aimed at designing and developing nanomaterials for the diagnosis and treatment of TNBC. The purpose of this study was to comprehensively evaluate the current status and trend of the application of nanomaterials in TNBC through bibliometric analysis. Studies focusing on nanomaterials and cancer were searched from the Web of Science core collection (WOSCC) database, and relevant literature meeting the inclusion criteria was selected for inclusion in the study. VOSviewer and CiteSpace were used to perform bibliometric and visual analysis of the included publications. A total of 2338 studies were included. Annual publications have increased from 2010 to 2024. China, the United States and India were the leading countries in the field, accounting for 66.1%, 11.5% and 7.2% of publications, respectively. The Chinese Academy of Sciences and Li Yaping were the most influential institutions and authors, respectively. Journal of Controlled Release was considered the most productive journal. Cancer Research was considered to be the most co-cited journal. Drug delivery and anti-cancer mechanisms related to nanomaterials were considered to be the most widely studied aspects, and green synthesis and anti-cancer mechanisms were also recent research hotspots. In this study, the characteristics of publications were summarized, and the most influential countries, institutions, authors, journals, hot spots and trends in the application of nanomaterials in cancer were identified. These findings provide valuable insights into the current state and future direction of this dynamic field.

Granulomatous lobular mastitis (GLM) presents significant challenges, including high rates of morbidity, recurrence, and disability, ultimately impacting women’s health and quality of life. Local autoimmune imbalance involving dysregulated cytokines and immune cells has been recognized to play a key role in the pathology of GLM. Traditional Chinese medicine (TCM), with its multi-component, multi-pathway and multi-target characteristics, offers unique advantages and broad prospects in the treatment of GLM. Here, we review the relationship between immune dysregulation and GLM, as well as the regulatory mechanisms of TCM-based interventions, with the aim of providing new insights and foundational knowledge for the clinical treatment of GLM, while promoting the further application and development of TCM-based strategies for the treatment of GLM.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is characterized by high invasiveness. Trastuzumab considerably improves the prognoses of HER2-positive BC, but some patients exhibit drug resistance. In this study, the effects of XLLXF combined with trastuzumab on the proliferation, apoptosis, invasion, and migration of HER2-positive BC cells are evaluated, and network pharmacology is performed. Then, we conduct an in vivo study using a xenograft mouse model of HER2-positive BC, and tumor growth is monitored. The expression levels of cytokines are measured by ELISA. Molecular docking is performed to observe the binding stability of IL2, JAK, STAT, and TNF with curcumenol, icariside-II, lobetyolin, and scutellarein. Finally, we observe changes in JAK1 and TNF-α in tumor tissues by immunohistochemistry. The results show that XLLXF enhances the inhibitory effects of trastuzumab on the proliferation, colony formation ability, migration, and invasion of HER2-positive BC cells and promotes apoptosis. Network pharmacology reveals that XLLXF may exert its effects on HER2-positive BC by modulating pathways such as the ErbB, JAK-STAT, and NF-κB pathways. Potential targets include cytokines closely related to immune function. In the in vivo study, XLLXF synergistically enhances the inhibitory effects of trastuzumab on tumor growth. ELISA reveals that XLLXF combined with trastuzumab increases the levels of IL-15, IL-2, TNF-α, and IFN-γ in tumor-bearing mice. Immunohistochemistry confirms that XLLXF can regulate the expressions of JAK1 and TNF-α. This study demonstrates that XLLXF can synergistically enhance the efficacy of trastuzumab in targeting HER2-positive BC. The mechanism may involve the modulation of inflammatory factors.

BACKGROUND:Traditional Chinese medicines are widely used in cancer treatment. Scutellaria barbata and Hedyotis diffusa herb pair (SH) has an anticancer effects in various tumors. However, the specific mechanism of SH in breast cancer remains unclear. METHODS:In the present research, we investigated the effect and regulatory network of SH in in breast cancer. CCK8, colony formation, transwell, wound healing and flow cytometry analysis were used for the detection of cell function. RESULTS:Ethyl acetate fraction from SH at an equal weight ratio (EA11) could inhibit the proliferation, migration and invasion of MCF7 and MDA-MB-231 cells. It also induced apoptosis in these two cell lines by downregulating Bcl2 and upregulating Bax and Cleaved-Caspase3. SH reduced the activation of the AKT/mTOR signaling pathway and the expression of p70S6K. Sequencing results showed that LMO1 was significantly downregulated in SH-treated cells compared with control cells. Importantly, overexpression of LMO1 attenuated the inhibitory effect of SH on cell proliferation and invasion and induced inflammatory tumor microenvironment. CONCLUSION:In conclusion, the SH herb pair inhibited the proliferation and metastasis through downregulating LMO1 expression and reducing the activation of the AKT/mTOR signaling pathway. LMO1 has the potential as a new target in the treatment of breast cancer.

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune “cold” and “hot” phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies.

The aim of this study was to explore the influences and underlying mechanisms of β-eudesmol on breast cancer (BC). Different concentrations of β-eudesmol (0, 10, 20, and 40 μM) were taken to treat BC cells. Cell Counting Kit-8, colony formation assay, and flow cytometry were performed to evaluate the influences of β-eudesmol on cell viability, proliferation, and apoptosis. To assess the influences of β-eudesmol on cell ferroptosis, the change of ROS, SOD, MDA, and intracellular iron and Fe2+ were determined. The protein changes of apoptosis, ferroptosis, and MAPK pathway (Bcl-2, Bax, cleaved caspase-3, SLC7A11, GPX4, SLC40A1, Transferrin, MEK1, and ERK1/2) were checked utilizing Western blot. In a concentration-dependent manner, β-eudesmol restrained cell viability and proliferation. β-eudesmol promoted cell apoptosis, as evidenced by the decline level of Bcl-2 and the raised level of Bax and cleaved caspase-3. β-eudesmol enhanced the level of ROS, MDA, iron, Fe2+, and Transferrin, and lessened SOD activity and the protein expression of SLC7A11, GPX4, SLC40A1, MEK1, and ERK1/2. Moreover, ferroptosis inhibitor Fer-1 and MEK1 overexpression both reversed the changes on cell proliferation, apoptosis, and ferroptosis induced by β-eudesmol. β-eudesmol inhibited cell proliferation and promoted cell apoptosis and ferroptosis via regulating MAPK pathway in BC.

Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.

Granulomatous lobular mastitis (GLM) is a benign and infrequent chronic breast ailment. Although this lesion can be clinically and radiographically mistaken for early-onset breast cancer, it is a rare occurrence for the two to coexist. This report describes three such cases. In all three patients, the primary signs and symptoms were related to the formation of diffuse breast masses or abscesses. Breast ultrasound and MRI revealed glandular edema and dilated breast ducts. The biopsies of all lesions exhibited both granulomatous inflammation confined to the lobules of the breast, abundant interstitial inflammatory cell infiltrates, and apparently cancerous cells located in dilated ducts with intact basement membranes. The surgically excised specimens confirmed the diagnosis of GLM and ductal carcinoma in situ (DCIS) in all three patients who underwent breast mass resection. By clinical imaging and clinical manifestations, GLM may obscure a concurrent DCIS, as highlighted by the cases reported herein.

目的:研究中药复方乳移平对人乳腺癌MCF-7细胞增殖和细胞周期的影响.方法:采用药物浓度递增法培养MCF-7细胞,随机分为空白对照组、乳移平组.CCK-8法检测细胞增殖水平,平板克隆形成实验检测细胞克隆能力,细胞迁移实验检测细胞水平迁移能力,流式细胞术检测不同药物对细胞周期及凋亡的影响,Western Blot检测蛋白水平的表达,明胶酶谱测定MCF-7细胞中MMP-9(matrix metalloproteinase-9,MMP-9)的活性.结果:CCK-8法显示,与空白对照组相比,乳移平组可抑制细胞增殖(P＜0.0001).平板克隆结果显示,与空白对照组相比,乳移平给药组细胞克隆率显著降低(P＜0.0001).划痕实验结果表明,乳移平给药组MCF-7细胞进入空腔的能力明显低于空白对照组(P＜0.05).侵袭实验表明,乳移平给药组同空白对照组相比,MCF-7细胞的侵袭细胞数明显减少(P＜0.05).流式细胞术结果显示,与空白对照组相比,乳移平给药组G2期细胞数量相对较少(P＜0.05).Western Blot结果表明,同阴性空白对照组相比,乳移平下调N-钙黏蛋白、Vimentin、Snail1和Snail2的表达,而上调E-钙黏蛋白的表达(P＜0.05).结论:乳移平对MCF-7乳细胞生长和侵袭的抑制作用,其机制可能是通过诱导细胞周期阻滞、减少MMP9的活性和抑制上皮-间质转化(EMT).

特发性肉芽肿乳腺炎(idiopathic granulomatous mastitis,IGM),又称肉芽肿性小叶性乳腺炎、肉芽肿性乳腺炎,是一种局限于乳腺小叶、以非干酪样坏死性肉芽肿为主要病理特征的慢性炎症性疾病,近年来在全世界范围内呈爆发性增长,尤其是年轻女性,大多数患者来自地中海地区(如土耳其、约旦)和亚洲(如中国、马来西亚)[1].

Objective: To observe the clinical effect of precise minimally invasive debridement under the guidance of color ultrasound combined with Yiqi Heying Chinese medicinal in treatment of granulomatous mastitis（GM）, to study the therapeutic mechanism of Yiqi Heying Chinese medicinal from the angle of immunity, thus to establish an optimal diagnosing and treating scheme for GM with TCM internal and external therapies. Methods: A total of 100 female patients with GM who met the inclusion criteria were randomly divided into the treatment group and the control group, with 50 cases in each group. The treatment group was treated with precise minimally invasive debridement under the guidance of color ultrasound combined with Yiqi Heying Chinese medicinal, whereas the control group was treated with conventional incision and drainage of abscess combined with cortin and antibiotics. Both groups were treated for 8 weeks. The range of inflammatory lesions in the abscess cavity and surrounding breast, the cure rate, the total effective rate, the rebound rate, the recurrence rate, the effective rate of the conservative treatment, breast appearance evaluation and other indicators were observed in the two groups. The changes of erythrocyte sedimentation rate（ESR）, C-reactive protein（CRP）, complement C3 and C4, IgA, IgG and IgM were observed before and after the treatment in the two groups. Results: 48 cases were completed in the treatment group and 47 cases in the control group. The cure rate of the treatment group was 43. 75%（ 21/48）, which was significantly higher than 29. 79%（14/47） of the control group（P ＜ 0. 05）; the total effective rate of the treatment group was 89. 58%（ 43/48）, which was significantly higher than 72. 34%（ 34/47） of the control group（ P ＜ 0. 05）. The rebound rate was 0%（ 0/48） and the recurrence rate was 8. 33%（ 4/48） in the treatment group, which were significantly lower than 23. 40%（11/47） and 25. 53%（12/47） in the control group（P ＜ 0. 05）. After one week of treatment, the range of abscess cavity and surrounding inflammatory lesions decreased by 12%-15% in both groups, and the effect of the control group was faster than that of the treatment group（P ＜ 0. 05）. However, in the control group, 11 cases rebounded in the second week, and the range of the abscess cavity remained unchanged or even increased; in the treatment group, the range of inflammatory lesions in the abscess cavity and surrounding area decreased continuously（P ＜ 0. 05）. The conservative treatment efficiency was 93. 75%（ 45/48） in the treatment group, which was significantly higher than 59. 75%（ 28/47） in the control group（ P ＜ 0. 05）. Breast appearance evaluation results was better in the treatment group than that in the control group（ P ＜ 0. 05）. The levels of ESR, CRP, IgA, IgG and IgM were decreased after the treatment compared with those before the treatment in the two groups; the decreases in the treatment group were more significant than those in the control group（ P ＜ 0. 05）. The levels of complement C3 and C4 were increased after the treatment compared with those before the treatment in the two groups; the increase of C4 was more significant in the treatment group than that in the control group（ P ＜ 0. 05）. Conclusion: Under the guidance of color ultrasound, the cure rate and effectiveness of precise minimally invasive debridement combined with Yiqi Heying Chinese medicinal are significantly better than those of the therapy of conventional external treatment plus cortin and antibiotics in treatment of GM, which corrects the immune imbalance of patients, and has obvious advantages in shortening the onset time, narrowing the range of inflammation, reducing the rebound rate and the recurrence rate, improving the effectiveness of conservative treatment and the satisfaction of breast appearance. An internal and external treatment scheme for GM can be established based on TCM advantages.

单细胞转录组测序是在单个细胞水平对mRNA进行高通量测序的技术.针对单个细胞研究其整体水平的基因表达情况,可解决细胞分子机制研究中常见的细胞异质性、细胞量少而无法进行常规高通量测序等难题.乳腺癌是一类异质性高的肿瘤,将单细胞转录组测序技术应用于乳腺癌的研究中,可以更好了解肿瘤异质性、肿瘤微环境、潜在的治疗靶点及治疗耐药等问题,有利于精确或个性化的肿瘤治疗模式的发展.