Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma

Pancreatic cancer (PC) is a cancer of the digestive system, and pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all PC cases. Exosomes derived from PDAC (PDAC-exosomes) promote PDAC development and metastasis. Exosomes are nanoscale vesicles secreted by most cells, which can carry biologically active molecules and mediate communication and cargo transportation among cells. Recent studies have focused on transforming exosomes into good drug delivery systems (DDSs) to improve the clinical treatment of PDAC. This review considers PDAC as the main research object to introduce the role of PDAC-exosomes in PDAC development and metastasis. This review focuses on the following two themes: (a) the great potential of PDAC-exosomes as new diagnostic markers for PDAC, and (b) the transformation of exosomes into potential DDSs.     

Changes in the National Endovascular Management of Femoropopliteal Arterial Disease: An Analysis of the 2011–2019 Medicare Data

PurposeTo describe national trends in the utilization of endovascular approaches (including balloon angioplasty, atherectomy, and stent placement) for the management of femoropopliteal peripheral arterial disease (PAD).Materials and MethodsThe Medicare Physician/Supplier Procedure Summary dataset containing 100% of Part B claims was interrogated for years 2011–2019. The Current Procedural Terminology codes specific for femoropopliteal angioplasty, stent placement, and atherectomy were used to create summary statistics for utilization by year, place of service (hospital inpatient, hospital outpatient, and office-based laboratory), and provider specialty (cardiology, radiology, and surgery).ResultsThe use of atherectomy increased from 34,732 (33%) procedures in 2011 to 75,435 (53%) procedures in 2019, and atherectomy became the dominant treatment strategy for femoropopliteal PAD. The relative utilization of stent placement (36,793 [35%] to 28,899 [20%]) and angioplasty only (34,398 [32%] to 38,228 [27%]) decreased concomitantly from 2011 to 2019. By 2019, the use of atherectomy was twofold higher in office-based laboratories than in the outpatient hospital setting (44,767 and 20,901, respectively). Treatment strategy varied by provider specialty in 2011 when cardiologists used atherectomy most frequently (17,925 [43%]), whereas radiologists used angioplasty alone (5,928 [6%]) and surgeons stented (18,009 [37%]) most frequently. By 2019, all specialties utilized atherectomy most frequently (29,564 [59%] for cardiology, 10,912 [58%] radiology, and 33,649 [47%] surgery).ConclusionsThe national approach to endovascular management of femoropopliteal PAD has changed since 2011 toward an implant-free strategy, including a multifold increase in the use of atherectomy. Discordant rates of atherectomy use between the ambulatory hospital and office-based settings highlight the need for comparative effectiveness studies to guide management.     

NRP-1单克隆抗体对乳腺癌裸鼠移植瘤生长的影响

 目的 探讨NRP-1单克隆抗体（NRP-1 MAb）的特异性，以及不同剂量的NRP-1 MAb治疗乳腺癌裸鼠移植瘤的疗效。方法 Western blot和共聚焦免疫荧光法检测NRP-1 MAb是否识别MCF7细胞上NRP-1蛋白。将MCF7细胞接种于BALB/c裸鼠皮下建立乳腺癌细胞移植瘤模型，并进行瘤组织传代。传代的肿瘤体积生长至300~500 mm3时，随机分为对照组、NRP-1 MAb低剂量组、中剂量组和高剂量组，每组6只，给药7次。观察荷瘤裸鼠一般状况，测量瘤体大小及裸鼠体重。实验结束时剥离瘤体称重，提取组织蛋白，Western blot检测组织中VEGF蛋白和NRP-1蛋白的表达量。结果 NRP-1MAb成功识别MCF7细胞上的NRP-1蛋白；NRP-1 MAb能够有效抑制MCF7细胞裸鼠移植瘤的生长，低剂量组（1 mg/kg）抑瘤率为47.01%，中剂量组（5 mg/kg）抑瘤率为65.70%，高剂量组（10 mg/kg）抑瘤率为69.19%。。结论 NRP-1 MAb能够识别并有效结合MCF7细胞膜上的NRP-1蛋白，且可抑制MCF7细胞移植瘤的生长，NRP-1 MAb抑制移植瘤的增长可能与下调NRP-1和VEGF表达有关。     

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.     

穴位贴敷联合风咳汤治疗感染后咳嗽的临床研究

目的:探究风咳汤联合穴位贴敷治疗感染后咳嗽的临床疗效,以期丰富治疗方法,为治疗感染后咳嗽提供科学依据。方法:选取2017年1月至2018年1月南京市中西医结合医院收治的感染后咳嗽患者88例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组44例。对照组予常规治疗,观察组在对照组基础上加用风咳汤联合穴位贴敷治疗,均治疗2周。观察比较2组患者采用不同方法治疗前、后中医证候积分、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、诱导痰上清液中P物质(SP)含量水平变化情况。治疗过程中收集不良反应资料,结束治疗后比较2组疗效。结果:1)2组患者完成治疗方案后,中医症候积分较治疗前均显著下降,观察组显著优于对照组,差异有统计学意义(P<0.05);2)治疗后2组患者IL-8、TNF-α、SP含量均较治疗前显著下降,且观察组优于对照组,差异有统计学意义(P<0.05);3)观察组患者临床控制率、总有效率明显高于对照组,差异有统计学意义(P<0.05)。4)2组患者ALT、AST、CCr、BUN水平和不良反应发生率比较,差异无统计学意义(P>0.05)。结论:风咳汤联合穴位贴敷治疗感染后咳嗽能提高疗效,降低炎性反应水平,改善症状和生命质量。     

神经内科实习医师血管超声教学的问题及改进方法

血管超声知识是神经内科实习同学的重要学习内容之一,但传统本科教学中对血管超声部分内容局限,使进入神经内科实习的医师血管超声基础知识薄弱,且还存在实践操作的缺乏、教学方式单一等问题,不能在短期内较好的理解及掌握血管超声知识,使得实习效果欠佳。本研究通过对神经内科实习医师血管超声教学中存在的问题进行分析,提出改进方法,可以通过加强实习医师对血管超声的解剖和血流动力学的学习,打牢基础知识,同时将实习医师进行分组,互为模特进行操作实践,在操作实践中加深理论知识的理解和应用。同时还可采用微课等多媒体教学方式,提高实习医师的学习兴趣,显著提高实习效果。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.