Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

彝药益元化腐汤浸膏对溃疡性结肠炎模型T细胞亚群干预机制研究*

目的研究彝药益元化腐汤调控T细胞亚群介导治疗溃疡性结肠炎的效应机制，为益元化腐汤临床应用治疗溃疡性结肠炎提供科学基础。方法 32只C57BL/6健康雌性小鼠随机分为正常组、模型组、益元化腐汤中剂量（4.05 g·kg-1）和高剂量组（8.1 g·kg-1），每组8只。除正常组，其余以自由饮水的方式给予3%葡聚糖硫酸钠（sodium dextran sulfate，DSS）诱导建立溃疡性结肠炎小鼠模型，每2 d更换1次饮用水，自饮用DSS第1天起，各组按相应剂量灌胃给药，每日1次，连续8 d；采用疾病活动指数（diseases activity index，DAI）和苏木精-伊红染色法（hematoxylin-eosin staining，HE）分别评价溃疡性结肠炎症状及结肠组织形态学变化；荧光定量PCR（qPCR）检测淋巴细胞T细胞亚群相关因子转录的相对表达水平；流式细胞术（flow cytometry）检测T细胞亚群中辅助性T细胞1（T-helper 1 cell, Th1）、辅助性T细胞17（T-helper 17 cell，Th17）和调节性T细胞（regulatory T cell，Treg）的表达水平。结果 与正常组比较，病理模型组小鼠体质量和结肠质量显著下降、结肠长度显著缩短（P<0.05或P<0.01）；与病理模型组比较，益元化腐汤组显著增加小鼠体质量、结肠质量及其长度（P<0.05或P<0.01），改善结肠病理损伤程度；流式细胞术检测结果显示，益元化腐汤药物干预显著下调γδTCR表达（P<0.05），且抑制Th1细胞（CD4+ IFN-γ+ T细胞）、Th17细胞（CD4+ IL-17+ T细胞）绝对数量和比例（P<0.01），然而对Treg细胞（CD4+ Foxp3+ 调节性T细胞）表达无明显影响。qPCR检测结果显示，益元化腐汤显著下调UC小鼠Th17细胞因子IL-17A和转录因子RORγτ mRNA表达（P<0.01）。结论 彝药益元化腐汤可能通过抑制Th17细胞诱导的炎症反应介导治疗溃疡性结肠炎。     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Update on pediatric corneal diseases and keratoplasty

Managing pediatric corneal disorders is challenging as the prognosis of pediatric keratoplasty depends on several factors. Advancements in the genetic basis of congenital corneal diseases and investigations in congenital corneal conditions provide a better understanding of pediatric corneal conditions. Surgeons performing keratoplasty in children now have a choice of various techniques. Evolving surgical techniques of anterior lamellar and endothelial keratoplasties have expanded the management interventions in these pediatric corneal morbidity conditions; however, considerable concerns still exist in association with corneal transplantation in infants and children. Outcomes in pediatric keratoplasty depend upon the preoperative indications, the timing of surgical intervention, intraoperative and postoperative factors including the patient/care givers’ compliance. Factors such as low scleral rigidity, higher rate of graft failure, need for frequent examinations under anesthesia, and difficulty in optimal visual acuity assessment still remain a considerable challenge in pediatric scenarios. In children, deprivation amblyopia as a result of the corneal opacification can adversely affect visual development, causing dense amblyopia. Outcomes to surgical interventions for management of corneal opacification in children are further compromised by the preexisting amblyopia apart from the concerns of refractive outcome of the graft. Graft rejection, graft infection, amblyopia, and glaucoma continue to be serious concerns. In recent years both anterior and posterior lamellar keratoplasty techniques are being increasingly performed in pediatric eyes, which offer advantages in the form of lower risk of graft rejection. The timing of surgery, careful case selection, cautious intraoperative approach, and optimal postoperative management can improve the anatomical and functional outcome in difficult cases.     

解偶联蛋白1基因多态性与2型糖尿病心脑血管并发症的相关性

目的探讨解偶联蛋白1(UCP1)基因多态性与2型糖尿病(T2DM)心脑血管并发症的相关性。方法选取2019年7月—2020年7月住院治疗的T2DM 440例,根据有无心脑血管并发症分为观察组(T2DM合并心脑血管并发症)221例和对照组(单纯T2DM)219例。比较两组一般资料,UCP1在rs45539933、rs10011540及rs1800592位点的基因型分布与等位基因频率;通过多因素Logistic回归分析评估T2DM发生心脑血管事件的危险因素。结果观察组病程长于对照组,糖化血红蛋白水平高于对照组,而血清高密度脂蛋白胆固醇水平低于对照组(P<0.01)。观察组C/C基因型分布及C碱基频率均高于对照组(P<0.05)。C/C基因型是T2DM患者发生心脑血管并发症的危险因素(P<0.05)。结论UCP1基因多态性与T2DM心脑血管并发症的发生显著相关。