ANGPTL6-mediated angiogenesis promotes alpha fetoprotein-producing gastric cancer progression

Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is regarded as a rare but highly malignant gastric adenocarcinoma subtype and its clinic pathological presentation mimics hepatocellular carcinoma. However, the underlying mechanism of this disease remains elusive. The level of ANGPTL6 in AFPGC cell lines is much higher than that of common types of gastric cancer cells. A high level of ANGPTL6 confers a poor prognosis and is correlated with the expression of CD34 (an endothelial cell marker). ANGPTL6 promotes endothelial cell migration and tube formation, Moreover, ANGPTL6 knockdown inhibits cancer cell apoptosis and invasiveness. Mechanistically, ANGPTL6 activates the ERK1/2 and AKT pathways. Treatment of ERK1/2 or AKT inhibitor can attenuated cell migration and tube formation. ANGPTL6 loss results in tumor growth in vivo. Our study revealed that ANGPTL6 is an important driver gene of angiogenesis in AFPGC development. These findings provide not only an effective biomarker for diagnosis but also an attractive therapeutic target for use in AFPGC patients.     

浅谈腹膜透析患者的血压管理

腹膜透析患者的高血压患病率达80%以上,难治性高血压导致卒中、心血管事件发病率不断增加,是患者死亡和退出腹膜透析的主要原因。2015年国际腹膜透析协会(ISPD)关于成人腹膜透析患者心血管和代谢指南指出,持续腹膜透析患者目标血压应<140/90 mmHg,并与年龄无关。腹膜透析患者血压控制不佳的影响因素纷繁复杂,但常见原因是容量超负荷和残肾功能减退。腹膜透析患者高血压防治策略包括容量负荷的准确评估与干预、残余肾功能的有效保护、透析处方的及时调整,降压药物的正确选择以及以病人为中心的团队管理等五个方面。     

维持性血液透析患者的血清硫化氢水平及其影响因素的分析

目的:研究维持性血液透析患者的血清硫化氢水平及其影响因素。方法:根据筛选及排除标准,纳入符合要求的维持性血液透析患者150例,同时收集健康志愿者17名作为健康对照。留取患者透析前后血标本,健康对照组则清晨空腹抽血。检测血清硫化氢、一氧化氮、一氧化氮/内皮素-1及硫化血红蛋白等水平,并作相关性分析。结果 :维持性血液透析患者透析前血清硫化氢、一氧化氮/内皮素-1比值、硫化血红蛋白水平明显低于健康对照组(P0.01),而内皮素-1和维生素B6含量与健康对照组差异无统计学意义(P0.05);透析前血清硫化氢与一氧化氮、一氧化氮/内皮素-1比值、硫化血红蛋白及肾小球滤过率正相关(P0.01),而与血肌酐水平负相关;透析后血清硫化氢水平较透析前明显上升,一氧化氮水平和一氧化氮/内皮素-1比值明显下降,而内皮素-1、硫化血红蛋白及维生素B6水平在透析前后无明显变化。结论:维持性血液透析患者血清硫化氢水平明显降低,其水平与一氧化氮、硫化血红蛋白、肾功能等显著相关;血液透析后患者血清硫化氢水平较透析前显著升高。     

Surgical management of decubitus ulcers

Decubitus ulcers are a significant source of morbidity and mortality in those populations affected^1–3: the elderly, the neurologically impaired, and paraplegics. Health care expenditures rise because of the increased length of hospital stay for patients with pressure ulcers. Treatment modalities and staffing time are increased considerably with the management of pressure ulcers both in the United States^1,4 and abroad.⁵ The magnitude of the decubitus ulcer problem has been compared to an epidemic in the British literature,⁵ and it is considered a serious public health concern by authorities in the United States.^4,6The literature abounds with reviews focusing on the epidemiology, etiology, pathophysiology, risk factors, prevention, and treatment of decubitus ulcers.^5–12 These aspects are addressed in this article to provide a clear understanding of the populations at risk for developing decubitus ulcers and of those pathophysiologic factors responsible for their development. Subsequently, preventive measures, management, and treatment modalities are discussed.     

Bone marrow mesenchymal stem cell-derived exosomal miR-193b-5p reduces pyroptosis after ischemic stroke by targeting AIM2

BackgroundIschemic stroke represents a major factor causing global morbidity and death. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (Exos) have important effects on treating ischemic stroke. Here, we investigated the therapeutic mechanism by which BMSC-derived exosomal miR-193b-5p affects ischemic stroke.Methodsluciferase assay was performed to evaluate the regulatory relationship of miR-193b-5p with absent in melanoma 2 (AIM2). Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed for the in vitro assay, while a middle cerebral artery occlusion (MCAO) model was developed for the in vivo assay. After exosome therapy, lactate dehydrogenase and MTT assays were conducted to detect cytotoxicity and cell viability, while PCR, ELISA, western blotting assay, and immunofluorescence staining were performed to detect changes in the levels of pyroptosis-related molecules. TTC staining and TUNEL assays were performed to assess cerebral ischemia/reperfusion (I/R) injury.ResultsIn the luciferase assay, miR-193b-5p showed direct binding to the 3ʹ-untranslated region of AIM2. In both in vivo and in vitro assays, the injected exosomes could access the sites of ischemic injury and could be internalized. In the in vitro assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on increasing cell viability and attenuating cytotoxicity; AIM2, GSDMD-N, and cleaved caspase-1 levels; and IL-1β/IL-18 generation. In the in vivo assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on decreasing the levels of these pyroptosis-related molecules and infarct volume.ConclusionBMSC-Exos attenuate the cerebral I/R injury in vivo and in vitro by inhibiting AIM2 pathway-mediated pyroptosis through miR-193b-5p delivery.