Vedolizumab as the First-Line of Biologicals for Pediatric Patients With Ulcerative Colitis

PurposeVedolizumab (VDZ) was reported to be effective as a first-line biological in adult ulcerative colitis (UC). The aim of this study was to investigate the safety and effectiveness of VDZ as the first-line biological in pediatric refractory UC.MethodsWe retrospectively extracted data from pediatric patients with UC who received first-line VDZ. The following were recorded: baseline characteristics; clinical activity of intestinal disease, levels of fecal calprotectin (FC), C-reactive protein, and serum amyloid A; and erythrocyte sedimentation rate. Clinical effectiveness, biochemical remission, and safety of VDZ were also investigated.FindingsEight patients were identified (median age, 12 years). FC levels were abnormal in all cases and were remarkably elevated in 3 patients. C-reactive protein, serum amyloid A, and erythrocyte sedimentation rate values were abnormal in 2, 4, and 5 patients, respectively. According to the pediatric UC activity index score, 1, 5, and 2 patients had mild, moderate, and severe disease. Fourteen weeks after VDZ administration, 5 patients achieved remission, and 3 remained in remission until week 52. Of the 3 patients who did not reach remission in week 14, two achieved remission by week 52. In week 52, five of the eight patients continued receiving VDZ and maintained remission. All patients achieved clinical remission without corticosteroid use. No adverse events were observed in any patient.ImplicationsVDZ may serve as a safe and effective first-line biological option for treating pediatric patients with UC. FC levels before VDZ administration may be predictive of long-term remission.     

TBS在监测及诊断骨质疏松方面的应用价值

利用DXA（dual energy X-ray absorptiometry,双能X线吸收法）测得的单位面积骨密度值（areal bone mineral density,BMD）是诊断骨质疏松的金标准。骨质疏松患者骨量减少的同时通常存在骨微结构的退化,表现为骨小梁数量减少、间距增加以及骨小梁间连接性下降,而BMD仅能显示骨量的变化,不能提供关于骨结构的信息。因此,仅靠BMD来诊断或排除骨质疏松是不全面的。骨小梁分数（trabecular bone score,TBS）是一种可由DXA图像获得的反映图像上灰阶变化的结构参数,能有效评估骨的微结构、描述骨的质量。本文将从TBS的检测方法、与其他检测骨折风险指标之间的关系以及TBS的有效性和不足等方面来介绍TBS在监测及诊断骨质疏松方面的应用价值。     

AS1411 Aptamer/Hyaluronic Acid-Bifunctionalized Microemulsion Co-Loading Shikonin and Docetaxel for Enhanced Antiglioma Therapy

In this study, we developed an AS1411 aptamer/hyaluronic acid-bifunctionalized microemulsion co-loading shikonin and docetaxel (AS1411/SKN&DTX-M). Such microemulsion was capable of penetrating the blood-brain barrier (BBB), targeting CD44/nucleolin-overexpressed glioma, and inhibiting the orthotopic glioma growth. AS1411/SKN&DTX-M showed a spherical morphology with a diameter around 30 nm and rapidly released drugs in the presence of hyaluronidase and mild acid. In the U87 cellular studies, AS1411/SKN&DTX-M elevated the cytotoxicity, enhanced the cellular uptake, and induced the cell apoptosis. In the artificial blood-brain barrier model, the transepithelial electrical resistance was decreased after the treatment with AS1411/SKN&DTX-M and thereby of increasing the apparent permeability coefficient. Furthermore, AS1411/SKN&DTX-M showed a strong inhibition against the formation of cancer stem cell–enriched U87 cell spheroids, in which the expression of CD133 was downregulated significantly. In the biodistribution studies, AS1411/SKN&DTX-M could selectively accumulate in the brains of orthotopic luciferase-transfected U87 glioma tumor–bearing nude mice. Importantly, AS1411/SKN&DTX-M exhibited the overwhelming inhibition of glioma growth of orthotopic luciferase-transfected U87 glioma models and reached the longest survival period among all the treatments. In summary, the codelivery of shikonin and docetaxel using bifunctionalization with hyaluronic acid and AS1411 aptamer offers a promising strategy for dual drug-based combinational antiglioma treatment.     

Preoperative Microvascular Invasion Prediction to Assist in Surgical Plan for Single Hepatocellular Carcinoma: Better Together with Radiomics

Annals of Surgical Oncology - Prediction models with or without radiomic analysis for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) have been reported, but the potential for...     

Survivin在造血系统肿瘤中的研究进展

Survivin是一种新的凋亡抑制蛋白(inhibitor of apoptosisprotein，IAP)，具有细胞周期调控和凋亡抑制双重功能。在多种造血系统肿瘤组织中高表达，与诊断、预后和耐药密切相关。利用survivin致敏的树突状细胞疫苗、survivin反义核酸及Survivin阴性突变体可有效抑制肿瘤细胞生长，为采用生物学策略治疗造血系统肿瘤开辟了新途径.本综述重点阐述了survivin在造血系统肿瘤中的表达，survivin与造血系统肿瘤预后和耐药的关系及survivin在造血系统肿瘤治疗中的应用。     

Adipose-derived mesenchymal stromal cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis

Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA), and adipose-derived mesenchymal stromal cells (ADSCs) can inhibit experimental collagen-induced arthritis model. This study aims to determine whether ADSCs also suppresses osteoclastogenesis and bone erosion in collagen-induced arthritis (CIA). Osteoclasts were induced from bone marrow-derived CD11b⁺ cells with receptor activator of nuclear factor-κ B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) stimulation and assessed with tartrate-resistant acid phosphatase (TRAP) staining. For human cells, osteoclasts were produced from human CD14⁺ cells. ADSCs were generated and added to cultures with different ratios with CD11b⁺ cells. Transwell and antibody blockade experiments were performed to define the mechanism of action. NF-κB and RANKL expression were determined by Western blotting and RT-qPCR. About 2 × 10⁶ ADSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with type II collagen/complete Freund's adjuvant (CII/CFA) while the onset and severity of the CIA were monitored. Adipose-derived mesenchymal stromal cells but not fibroblast cells completely suppressed osteoclastogenesis in vitro for human and mice. ADSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with ADSCs dramatically decreased the levels of NF-κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. We have demonstrated that ADSCs can inhibit RANKL-induced osteoclasts genesis via CD39 signals. Our findings also suggest that ADSCs can inhibit osteoclasts genesis without the involvement of regulatory T cells. ADSCs might represent a promising strategy for stem cell-based therapies for RA. Thus, manipulation of ADSCs may have therapeutic effects on RA and other bone erosion–related diseases.