Background Triple-negative breast cancer is a particularly aggressive type of breast cancer that is closely associated with abnormal vascularization within the tumor. However, traditional anti-VEGF therapies and other treatments have limited efficacy. Tumor-associated macrophages (TAMs) induce and regulate tumor angiogenesis. In recent years, regulating TAMs polarization has become a hot topic for research with objectives to normalize tumor vasculature and improve drug delivery and the tumor microenvironment. Our previous studies have found that peritumoral electroacupuncture (EA) can regulate tumor angiogenesis, but the underlying mechanism remains unclear. Methods In this study, we examined the phenotype of TAMs and inflammatory factors to observe the effect of peritumoral electroacupuncture on the phenotypic polarization of TAMs. Based on this, we evaluated the structure and function of tumor vasculature. Finally, we conducted a preliminary exploration of the mechanism underlying the regulation of TAMs phenotypic polarization by peritumoral electroacupuncture. Results In this study, we found that peritumoral electroacupuncture could promote the phenotypic polarization of TAMs toward the M1 type, thereby reducing microvascular density in tumor tissue, increasing pericyte coverage, improving the stability of the basement membrane, promoting vascular maturation, and enhancing perfusion while reducing tissue hypoxia. Conclusions Peritumoral electroacupuncture can promote the phenotypic polarization of TAMs toward the M1 type, leading to normalization of tumor vascular structure and function. The mechanism may be related to the downregulation of glyoxalase-1 and subsequent activation of the MGO-AGEs/RAGE axis.
Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.
BACKGROUND:Huaier (Trametes robiniophila Murr), a traditional Chinese medicine, is widely used in China as a complementary and alternative therapy to treat hepatocellular carcinoma (HCC). Past studies have shown that Huaier can arrest the cell cycle, promote apoptosis and inhibit the proliferation of cancer cells. However, how it regulates the metabolism of HCC is still unclear. OBJECTIVE:This study explores the metabolic-related function of Huaier in treating HCC with an in-silico approach. METHODS:A network pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of metabolic reprogramming in HCC with Huaier. The compounds of Huaier were obtained from public databases. Oral bioavailability and drug likeness were screened using the TCMSP platform. The differential gene expressions between HCC and non-tumor tissue were calculated and used to find the overlap from the targets of Huaier. The enrichment analysis of the overlapped targets by Metascape helped filter out the metabolism-related targets of Huaier in treating HCC. Protein-protein interaction (PPI) network construction and topological screening revealed the hub nodes. The prognosis and clinical correlation of these targets were validated from the cancer genome atlas (TCGA) database, and the interactions between the hub nodes and active ingredients were validated by molecular docking. RESULTS:The results showed that Peroxyergosterol, Daucosterol, and Kaempferol were the primary active compounds of Huaier involved in the metabolic reprogramming of HCC. The top 6 metabolic targets included AKR1C3, CYP1A1, CYP3A4, CYP1A2, CYP17A1, and HSD11B1. The decreased expression of CYP3A4 and increased expression of AKR1C3 were related to the poor overall survival of HCC patients. The molecular docking validated that Peroxyergosterol and Kaempferol exhibited the potential to modulate CYP3A4 and AKR1C3 from a computational perspective. CONCLUSION:This study provided a workflow for understanding the mechanism of Huaier in regulating the metabolic reprogramming of HCC.
目的 通过分析中国临床试验注册中心(Chinese clinical trial registry,ChiCTR)注册的与中医药干预癌因性疲劳(cancer-related fatigue,CRF)相关的临床试验,探讨其试验注册现状.方法 检索ChiCTR数据库收录的从建库至2022年6月2日与中医药相关的CRF临床研究注册试验,对检索结果进行筛选并提取所需数据信息,运用WPS Office软件的表格功能对纳入研究数据进行统计分析,并归纳临床试验特征.结果 最终纳入36项CRF中医药相关临床试验,覆盖全国6个省、3个直辖市,其中包括干预性研究34项,观察性研究2项,招募样本量5 327例,干预措施包括内服药物疗法、中药注射液、外治法和中医传统功法.结论 目前有关CRF中医药临床试验注册数量总体呈上升趋势,试验以随机对照试验(randomized controlled trial,RCT)研究居多,干预性研究为主,其空间分布欠均衡,且注册信息的严谨性与结局指标的规范性待进一步提高.
Objective:To analyze the expression and clinical significance of SHC SH2-binding protein 1(SHCBP1)in lung adenocarcinoma(LUAD).Methods:Oncomine,TIMER,UALCAN,GEPIA,Kaplan-Meier plotter and STRING databases were used to explore the effect of SHCBP1 on progression and immune infiltration of LUAD.Results:Expression of SHCBP1 mRNA in LUAD tissue was significantly higher than that in normal lung tissue(P<0.05).Expression of SHCBP1 mRNA was significantly increased in LUAD patients with smoking history,nodal metastasis,late clinical stage and TP53 mutation(P<0.05).Survival analysis by GEPIA and Kaplan-Meier plotter databases showed that LUAD patients with high SHCBP1 mRNA expression had a lower overall survival rate(P<0.05).SHCBP1 mRNA was correlated with immune cell infiltration,immune cell markers and immune checkpoint expression in LUAD.Conclusion:High expression of SHCBP1 is related to poor prognosis and tumor immune infiltration of LUAD patients.
目的:分析郝万山教授治疗抑郁症的组方用药规律.方法:筛选 2015 年 5 月至 2020 年 1 月郝教授于北京中医药大学国医堂诊治的抑郁症病例,依据标准录入相关数据,应用中医传承辅助平台(V3.0)及SPSS 25.0,通过分析用药频次、四气五味、关联规则及聚类分析总结郝教授治疗抑郁症的组方用药规律.结果:筛选出符合标准的 495 个处方,涉及中药 170 味;中药频次前 3 位为陈皮、党参、石菖蒲;药性与药味以温、平及甘、辛、苦为主;高频药物组合前 3 位为"党参+陈皮""陈皮+石菖蒲""党参+石菖蒲";分析得到 30个药物组合关联规则;聚类分析得出 4 个核心聚类处方;常用经方有逍遥散,定志小丸等.结论:郝教授治疗抑郁症多从扶正气、宁心神、解郁结、化痰饮论治.
目的 采用数据挖掘联合网络药理学分析中医药治疗放射性肺损伤的用药规律及其潜在作用机制.方法 计算机检索知网、万方、维普、中国生物医学文献服务系统自2000年1月至2021年6月发表的中医药治疗放射性肺损伤的相关文献,采用频数统计、关联规则分析等对纳入处方进行分析,筛选治疗放射性肺损伤的高频核心药组.运用网络药理学方法获取高频核心药组的有效活性成分并预测其作用靶点.通过公认的疾病数据库收集放射性肺损伤疾病靶点,然后将药物靶点与疾病靶点取交集,并对核心靶点进行蛋白互作网络分析和KEGG信号通路富集分析.结果 共筛选出符合条件文献154篇,含178首方剂,涉及214味中药,使用频次>30次的中药21味.挖掘出高频药物间关联性最强的中药有6味,即为高频核心药组.高频核心药组与放射性肺损伤相关交集靶点97个,蛋白互作分析结果显示高频核心药组治疗放射性肺损伤的核心靶点可能是TP53、AKT1、INS等,KEGG通路富集结果涉及PI3K-Akt信号通路、HIF-1信号通路、MAPK信号通路等.结论 中医药治疗放射性肺损伤的以养阴益气为主,同时配合清热、化痰止咳平喘和活血化瘀.高频核心药组可能通过抑制炎性渗出、调节免疫平衡、减少肺组织细胞凋亡、修复损伤肺组织等方面治疗放射性肺损伤.
从厥阴角度分析胰腺癌的核心病机,并结合胰腺癌的临床症状与病理特点,将其总结为厥阴脏寒、肝阳不足.基于乌梅丸主治厥阴脏寒的理解,根据胰腺癌的原发部位、转移灶和临床表现,在乌梅丸的基础上灵活加减用药,在临床可收到较好的疗效.
To analyze the research status of acupuncture and moxibustion for cancer at home and abroad in the past 45 years by using bibliometric and scientific knowledge map methods,and explore the development trends in future. The literature of acupuncture and moxibustion for cancer was retrieved from CNKI and Web of Science (WOS) till December 31, 2020 since the database establishment, and CiteSpace and VOSviewer software were used to perform visual map analysis through cooperation network, keyword co-occurrence, keyword timeline, keyword emergence and other methods. Totally, 1 585 literature in CNKI and 1 564 literature in WOS were included, and the annual publication amount showed a fluctuating upward trend. Cooperation between countries was centered on China and the United States, and there was relatively little cooperation among different institutions. The analysis of keyword and cited literature showed that researches focused on the control of acupuncture and moxibustion therapy on cancer complications and adverse reactions of western medicine. The main research types in WOS were systematic review and randomized controlled trial (RCT), while in CNKI was review, depth studies on mechanism of acupuncture and moxibustion for cancer were rare. The concern about the quality of life of cancer patients may become research emphasis in the field of acupuncture and moxibustion for cancer in future, and the research scope tends to integrative and holistic oncology.
目的 探讨合并肾细胞癌(RCC)的多原发恶性肿瘤(MPMN)的发病特点、治疗方法及预后,以提高其临床诊治水平.方法 回顾性分析9例合并RCC的MPMN患者的临床资料,并随访生存情况.结果 9例患者中,男5例,女4例,确诊时患者的年龄为43~82岁.双原发恶性肿瘤(DPMN)7例,三原发恶性肿瘤2例.合并RCC的MPMN以消化系统和呼吸系统肿瘤最为常见.9例患者的中位生存时间为25个月,2年和3年生存率分别为66.7%和22.2%.结论 对恶性肿瘤患者定期随访可以在早期发现其他原发恶性肿瘤,通过临床分析提高对合并RCC的MPMN的认识也将有助于为患者制订恰当的治疗方案.
冷冻消融术是一种肿瘤微创治疗,具有局部消瘤作用确切、不良反应小、安全性高等优势,并能激发体液免疫和细胞免疫,甚至诱导远处病灶消失即远位效应,因此具有局部和全身双重治疗效应.然而,冷冻消融引起的免疫效应可能出现免疫增强、免疫无应答或免疫抑制,这与癌症类型、坏死/凋亡比例、冷冻范围、冷冻速率、冷冻数量等密切相关.冷冻消融可增大坏死/凋亡比例,联合细胞过继疗法、粒细胞-巨噬细胞集落刺激因子、免疫检查点抑制剂、Toll样受体激动剂能够增强全身性免疫效应.然而,如何利用、加强冷冻消融的远位效应仍然是治疗肿瘤,尤其是晚期肿瘤的关键.
目的 采用网状Meta分析方法比较冷冻消融、射频消融或微波消融单独或联合治疗原发性肺癌的疗效,为临床提供循证依据.方法 全面检索CNKI、维普、万方、the Cochrane Library、PubMed、Embase等数据库公开发表的关于冷冻消融、射频消融或微波消融治疗原发性肺癌的临床随机对照试验,检索时间为2016年1月至2020年7月,筛选出符合纳入标准的研究,按照Cochrane 5.1手册对纳入的研究进行文献质量评价与偏倚风险评估,采用ADDIS软件进行网状Meta分析与等级概率排序.结果 共纳入28项研究,2336例患者.一致性模型检验结果显示,微创消融联合化疗的疗效优于化疗或微创消融单独应用;在提高肿瘤控制率和1年生存率方面,冷冻消融、射频消融或微波消融联合或单独应用无明显差异.等级概率排序结果显示,冷冻消融联合化疗和微波消融联合化疗的疗效相近,且均有可能优于射频消融联合化疗.结论 联合疗法的疗效优于单独应用化疗或微创消融,冷冻消融和微波消融在控制肿瘤进展方面的效果更好,但在提高远期生存率方面无明显差异,但冷冻消融联合化疗有可能是更好的临床选择.