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.     

Ovine Iliac Vein Model for Endovascular Thrombectomy of Acute Deep Venous Thrombosis

An ovine iliac vein thrombosis model was devised to test a wall-contacting rotational thrombectomy device. Thrombosis was successfully induced in 9 sheep with an average clot length of 31 mm ± 12 and >60% vessel occlusion on angiography. The thrombus was subsequently removed, maintaining normal intraoperative pulmonary arterial pressure (5.9 mm Hg ± 3.6) and complete distal reperfusion after thrombectomy. Additionally, the sheep were without signs of vascular trauma or embolic complications on gross necropsy and histopathologic analysis. The findings from this study support the use of an ovine iliac deep vein thrombosis model for testing of a lower extremity thrombectomy device.     

特发性肺纤维化急性加重期证候与血清生物标志物的相关性研究＊

目的 通过分析特发性肺纤维化急性加重期（AE-IPF）患者证候与血清生物标志物的关系，为中医辨证治疗提供参考。方法 采用观察性研究设计，收集2019年3月至2019年11月三个中心的AE-IPF患者76例，其中痰热壅肺证26例、痰浊阻肺证50例，并纳入健康志愿者10例作为对照。采用ELISA测定患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平，分析与中医证候的相关性。结果 AE-IPF患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平均显著高于健康对照组。血清CCL18、HMGB1、KL-6、MMP-7和SP-D水平在痰热壅肺证和痰浊阻肺证患者间无显著性差异（P＞0.05），而血清SP-A水平存在显著性差异（P＜0.05）。结论 血清SP-A与AE-IPF证候存在一定的相关性，血清SP-A的浓度升高，与痰热壅肺证关系越密切，反之，血清SP-A浓度降低，则与痰浊阻肺证关系越密切。AE-IPF痰热壅肺证患者的预后可能较痰浊阻肺证患者更差。     

原发性肺鳞癌中EGFR和ALK基因突变的临床研究北大核心

目的:探讨赣南地区原发性肺鳞癌患者EGFR和ALK基因突变的特点,科学指导此类患者优选靶向用药。方法:入组73例原发性肺鳞癌病例,采用ARMS-PNA技术检测EGFR基因第18、19、20、21外显子突变,应用不平衡法检测其中60例病例的ALK融合基因,回顾性分析EGFR和ALK基因突变患者的临床病理特征。结果:EGFR基因突变8例,阳性率为10.96%(8/73),4例为L858R突变,3例为19del突变,1例为G719X突变。女性患者突变率(66.67%,2/3)明显高于男性患者(8.57%,6/70)(P=0.030),EGFR基因突变在高龄(≥60岁)、进展期(N_(1-3)、Ⅲ+Ⅳ期)患者中相对较高,但差异无统计学意义(P>0.05)。EGFR基因突变与吸烟史、T分期以及肿瘤分布位置均无相关性(P>0.05);ALK融合基因表达2例,阳性率3.33%(2/60),与患者性别、年龄、吸烟史、TNM分期及肿瘤分布类型等各临床病理特征均无相关性(P>0.05);未发现EGFR和ALK基因共存突变病例。结论:赣南地区原发性肺鳞癌患者EGFR和ALK基因突变率相对不高,EGFR基因突变以L858R和19del突变为主,且好发于女性患者,可能是患者病情进展的预测因子之一。     

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。     

Diagnosing pulmonary thromboembolism: Concerns and controversies

Pulmonary thromboembolism (PTE) is an important cause of mortality/morbidity even today despite advancement in clinical understanding as well as diagnostic facilities. Clinical diagnosis of PTE is often challenging because of nonspecific sign/symptoms. Adherence to clinical decision-making protocols and appropriate use of diagnostic modalities like computed tomography pulmonary angiography can resolve the diagnostic dilemma in most cases and help in the overall management of PTE. This article deals with various concerns as well as controversies surrounding accurate diagnosis of PTE as on date.