A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

ABSTRACT

Purpose

New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates.     

后路枕骨髁螺钉技术研究进展

正枕骨、寰椎和枢椎共同构成了枕颈部活动的结构功能单位,即枕颈交界区~([1-2])。炎症、创伤、肿瘤及畸形等因素会导致枕颈交界区失稳,从而引起颈脊髓或神经根的损伤、麻痹及难以忍受的疼痛,甚至危及生命~([3-4])。后路内固定融合技术是治疗枕颈部失稳的重要手段,目前常用术式为枕骨螺钉技术,该技术较钢丝固定技术有更好的生物力学稳定     

Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.     

不同区域晶状体上皮细胞基因表达差异分析

【目的】比较不同区域猪晶状体上皮细胞的基因表达在转录组水平上的差异。【方法】解剖显微镜下分离晶状体前囊膜，将附着于其上的上皮细胞分为中央（直径为10．56mm）和周边两部分。分别提取两个样本的总RNAs并经PCR扩增，以Cy3和Cy5分别标记扩增的中央与周边部分的cDNA。与含7548个基因的表达谱芯片杂交，经图像分析，生物信息学处理获得基因表达在转录水平差异的相关信息。【结果】中央与周边区域的猪晶状体上皮细胞在转录组水平共鉴定出952个有效表达的基因点，其中差异表达基因261个．以中央区域为参照，周边上皮细胞mRNA上调137个，下调124个。差异表达基因主要涉及的功能有：细胞周期与凋亡、细胞骨架蛋白及细胞外基质、转录、细胞信号分子等。【结论】中央与周边区域猪晶状体上皮细胞基因表达在转录组水平上差异明显。这类差异呈明显的功能聚类。     

上肢骨肿瘤切除后的自体骨移植重建

目的探讨应用自体骨移植对上肢骨肿瘤切除后的骨缺损修复重建的效果。方法1998年8月～2004年3月，收治上肢骨肿瘤切除后的骨缺损16例。男8例，女8例。年龄7～45岁。经病理确诊，肱骨近端尤文肉瘤和骨肉瘤各1例；肱骨远端尤文肉瘤2例；桡骨远端骨巨细胞瘤8例，高分化软骨肉瘤2例，恶性纤维组织细胞瘤和骨肉瘤各1例。2例肱骨近端肿瘤行自体锁骨代肱骨；2例肱骨远端肿瘤行自体腓骨代肱骨；12例桡骨远端肿瘤中，1例行自体髂骨移植，11例行自体腓骨代桡骨进行重建。采用MSTS系统进行术后功能评价。结果2例肱骨近端自体锁骨移植患者分别随访36个月和12个月，术后保持部分肩关节前屈和后伸功能，但外展功能丧失；MSTS评分分别为23分和22分。2例肱骨远端自体腓骨移植患者分别随访4个月和6个月，肘关节功能良好，移植骨连接处已经出现骨愈合；MSTS功能评分分别为24分和19分。12例桡骨远端自体骨移植患者中11例随访6～75个月，功能良好，无明显并发症；1例髂骨植骨的桡骨远端骨巨细胞瘤术后3个月移植骨完全愈合，至今随访75个月，肿瘤无复发。MSTS功能评分18~27分，平均22．6分。结论自体骨移植在上肢骨肿瘤切除后骨缺损的重建，尤其是儿童的骨缺损重建中，是一种较好的方法。     

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

直肠癌切除前后腹腔冲洗液脱落细胞学对比研究

目的研究直肠癌术中腹腔多次冲洗，对于降低患者腹腔内脱落癌细胞阳性率的临床意义。方法对63例直肠癌患者术中腹腔冲洗分6次进行，肿瘤切除前3次，切除后3次；将6次腹腔冲洗液行常规病理学涂片细胞学检查结果进行对比。结果肿瘤切除前，全组患者腹腔冲洗液脱落癌细胞均呈阳性表达。肿瘤切除后第1次腹腔冲洗液脱落癌细胞阳性40例，第2次阳性33例，第3次阳性13例。肿瘤切除后第1次冲洗液的脱落癌细胞阳性结果与切除后第2次冲洗液阳性结果比较，P〉0.05，差异无统计学意义；但第3次冲洗液的脱落癌细胞阳性结果与第2次比较，P〈0.01，差异有统计学意义。结论对直肠癌患者进行术中多次腹腔冲洗可降低腹腔内脱落癌细胞的阳性率。