Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.     

Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio

BackgroundDual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI).ObjectiveThe present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI).MethodsWe designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant.ResultsCompared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05).ConclusionTAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

Exosomes from miRNA‐126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke

AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXs^miR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXs^miR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

直线吻合器在全喉切除术中的应用

目的探讨一次性直线型吻合器在喉癌手术中的应用效果。方法选取我科2019年10例全喉切除手术患者,采用随机分组方法,分为封闭法和半封闭法两组。总结比较所用手术时间、术中出血量、术后咽瘘感染的发生率。结果所有手术都顺利完成,会厌软骨残留1例,咽瘘1例。结论直线吻合器在全喉切除术中具有较好的临床应用价值。     

扶正消瘤颗粒对原发性肝癌血清中VEGF、HIF-1α表达的影响及临床意义＊

目的 探讨扶正消瘤颗粒对原发性肝癌血清中血管内皮生长因子（Vascular endothelial growth factor，VEGF）和缺氧诱导因子-1α（Hypoxia inducible factor-1α，HIF-1α）表达的影响及临床意义。方法 选择符合纳入标准的原发性肝癌患者66例，按1∶1随机分试验组和对照组。观察治疗过程中两组VEGF、HIF-1α水平的变化及对患者临床疗效指标的影响。结果 （1）在性别、年龄、合并乙型肝炎、Child-Pugh分级、AFP值、临床分期方面，试验组和对照组差异无统计学意义（P > 0.05）。（2）肝癌患者在治疗各时间节点的VEGF和HIF-1α表达水平呈线性正相关（r = 0.829，P < 0.001）。（3）VEGF浓度在经导管动脉化疗栓塞术（Transcatheter arterial chemoembolization，TACE）后3月降至术前水平（P > 0.05），HIF-1α在TACE后3月仍高于术前（P < 0.05）。（4）扶正消瘤颗粒可降低HIF-1α水平，下调VEGF的表达。（5）扶正消瘤颗粒可减少TACE序贯RFA治疗后的不良反应，提高患者的生活质量（P < 0.05）。（6）血清中VEGF水平与生活质量无明显相关性（P > 0.05，r = 0.251），HIF-1α水平与生活质量存在正相关性（P < 0.05，r = 0.450）。结论 扶正消瘤颗粒可明显改善TACE序贯RFA治疗后患者生活质量，降低HIF-1α水平，下调VEGF的表达，抑制肿瘤血管生成。